key: cord-0010255-rovpo5fj
authors: nan
title: 1‐E3: COPD 4
date: 2013-10-18
journal: Respirology
DOI: 10.1111/resp.12184_20
sha: 373b683ec67c041d1b8c5fb3f3a59a73eee46463
doc_id: 10255
cord_uid: rovpo5fj

nan

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with clinical response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib in patients with non small cell lung cancer (NSCLC). However, distribution or biological significance of EGFR antibody in NSCLC patients is not yet investigated. In this study, we investigated whether IgG responses to EGFR derived peptides of NSCLC patients, and report that IgG against EGFR derived peptides were detectable in NSCLC patients treated with gefitinib, and they could be possible prognostic factor for progression free (PFS) and overall survival (OS) of NSCLC patients who received gefitinib treatment. Luminex system were used to measure immunoglobulins (Igs) to each of 58 different peptides in 42 NSCLC patients who were treated with gefitinib. Some kinds of anti-peptide IgG was detected in NSCLC patients and associated with PFS and OS. Detection of EGFR-derived peptide antibody from sera may be promising method for predicting the prognosis of NSCLC patients treated with gefitinib. These results could provide new insight for better understanding of humoral responses to EGFR-derived peptides in NSCLC patients.

Introduction This is a case of R.B, a 71 year old female presenting with 2 months history of anorexia and weight loss associated with shortness of breath. Ct scan revealed speculated nodular lesion left upper lobe. CT guided biopsy which showed Squamous Cell Carcinoma poorly differentiated. Patient underwent exploratory thoracotomy with left lobectomy. Metastatic work up such as Bone scan and Ct scan of the abdomen were negative for metastatic spread. Histopathology of tumor specimen revealed a combined tumor: Large cell carcinoma with focal neuroendocrine differentiation (CEA negative and NSE positive. Adenocarcinoma moderately differentiated (CEA positive and NSE negative, Mucicarmine positive). Discussion Large cell neuroendocrine carcinoma (LNEC) is a rare and aggressive neoplasm of lung with a very poor prognosis. It accounts for approximately 1.6 to 3.1% of all lung cancers. Overall incidence of Large cell neuroendocrine carcinoma (LNEC) ranges from 2.1 to 3.1% as reported in case series and even presents with a smaller percentage for the mixed or combined type. Chest pain is the most common presentation. Local data of its true incidence is unknown since there is no existing registry for such tumors. Immunohistochemistry is seldom routinely performed in other institutions. Thus, after an intensive search no prior study was found. Conclusion Diagnosis of LCNEC is often difficult, and requires histological analysis, cytological evaluation and immunohistochemistry. Prognosis of LCNEC is poor, the 5 year overall survival rate for LCNEC at 27% and 21%, Treatment is similar to small cell carcinoma however no standard adjuvant therapy regimen has been developed.

Inflammatory mediators are involved in the pathogenesis of airway inflammation. However, it has not been fully discussed about the role of prostaglandin E1 (PGE1) in cough, a common symptom of bronchial asthma. The effect of limaprost, a PGE1 anlogue, on cough response to inhaled capsaicin was examined in 21 patients with stable bronchial asthma in a randomized, placebo-controlled cross-over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold did not change after two-week treatment with limaprost (30 μg 3 times a day orally) compared with placebo. These findings indicate that PGE1 does not affect airway cough reflex sensitivity in asthmatic airway.

Characteristic HRCT findings of six patients with multiplc cystic lung disease (MCLD) is presented, which in the presence of supportive investigations can help in establishing the diagnosis and may obviate the need for lung biopsy. Case 1: Lymphangioleiomyomatosis: A 48 years old non smoker house wife on HRCT chest had multiple variable sized thin walled cysts distributed uniformly throughout lung fields from apices to bases with intervening normal lung parenchyma and a right sided loculated pneumothorax. Case 2: Idiopathic Pulmonary Fibrosis: A 70 years old male with IPF on HRCT chest had temporally heterogenous linear infiltrates of fibrotic foci and honey comb cysts of variable sizes located predominantly in peripheral lung regions especially in lower lobes. Case 3: Alpha-1 Antitrypsin Deficiency Emphysema: A 35 years old non smoker male's HRCT showing widespread hypoattenuating spaces with very thin/barely visible walls (especially in lower lobes) due to loss of lung parenchyma and decreased vascularity with apparently preserved upper lobes attenuation. Case 4: Emphysema due to Tobacco Smoking: A 59 years old COPD patient on HRCT chest revealed centrilobular lesions of low attenuation of variable sizes with very thin walls having predominant location in upper lobes consistent with centrilobular emphysema. Case 5. Lymphoid Interstitial Pneumonia: A 45 years old male having Sjogren's syndrome on HRCT chest showed cysts with well defined walls having random distribution with predominant involvement of central portions of lungs mostly involving upper lobes especially on the right side with interspersed normal lung parenchyma. Case 6: Advanced Cystic Bronchiectasis: A 36 years old never smoker male with advanced bronchiectasis on HRCT chest had extensive cylindrical, varicose and cystic bronchiectasis involving all lobes.

MAGIC syndrome (Mouth and Genital ulcers with Inflamed Cartilage) was first described by Firestein in 1985. It is thought to be a combination of Relapsing Polychondritis and Behcet Disease. Since then there were few cases published. We describe a young female who presented with severe disease necessitating tracheotomy during pregnancy and discuss the management, followed by review of the literature. A 33 years old Jordanian female attended our ENT clinic for assessment of hoarseness of voice and cough. She had repeated attacks of hoarseness of voice and difficulty of breathing in the past for which she responded to oral steroids. No definite diagnosis was given to the patient although asthma was suggested. In the ENT clinic examination then showed airway inflammation and crusting and so impression of Rhinoscleroma was made and she was found to be pregnant her steroids were stopped. She presented after 1 week with upper airway obstruction which necessitated emergency tracheotomy. Review of her history revealed recurrent mouth & genital ulcers & difficult intubation in the past during her LSCS. Blood investigations revealed ESR 60, CRP 0.1, negative ANA, RF & ANCA. Analysis for HLA B51 and HLA B52 was negative. Radiology and bronchoscopy showed significant subglottic stenosis. Bronchoscopy & tissue biopsy confirmed the presence of an inflamed cartilage. Patient was managed with steroids and Azathioprine. After delivery of her child she was reassessed, tracheostomy capped and she had undergone dilation of the stenosed segment. MAGIC syndrome is a rare disease and even challenging when it presents in pregnancy. Despite reports of abortion and premature birth but the patient was critical and given Azathioprine without complications. The long term outcomes are not clear due to paucity of data. Our patient has improved steadily. This is the first case of MAGIC syndrome diagnosed and managed during pregnancy. Metastatic pulmonary calcification is a rare disease and characterized by diffuse calcium deposition in the lung is known to occur in patient with chronic renal failure. However, this disease is uncommon and has only been detected in a few patients with severe disorders. A 50-year-old man with chronic kidney disease had progressive dyspnea. A chest radiograph showed poorly defined bilateral multiple nodular opacities in the superior to middle lung fields. An axial computed tomography of the chest showed ground-glass nodular opacity of alveolar pattern with focal consolidation relatively preserved peripheral and lower area. The radiologic images were suggestive of infection and diffuse alveolar hemorrhage. Bronchoscopic bronchoalveolar lavage (BAL) fluid had bloody color fluid and hemosiderin laden macrophages were shown. Before confirm lung biopsy, we treated IV steroid therapy for diffuse alveolar hemorrhage. But, the patient did not improve his symptom. Lung biopsy showed that calcium deposited in the alveolar septa. In addition, 99 mTc bone scintigraphy and SPECT/CT findings showed an intense uptake in both lungs. Finally we diagnosed metastatic pulmonary calcification. There was no calcium disorder in this patient. In contrast to the benign course of pulmonary calcification in most patients, some fulminant pulmonary calcifications complicating chronic kidney disease or hypercalcemia have been described. In chronic kidney disease patient, metastatic pulmonary calcification should be considered in the differential diagnosis of patients presenting with respiratory symptoms or pulmonary lesions in chronic kidney disease, especially combined calcium disorder. Background and Aim of Study The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib benefits some non-small cell lung cancer (NSCLC) patients, but most do not respond (primary resistance). Vascular endothelial growth factor (VEGF) targeted recombinant humanized monoclonal antibody bevacizumab has been used for many types of cancers such as NSCLC. As EGFR TKI resistance is not completely understood, this study was aimed to investigate whether dual inhibition of VEGF and EFGR pathways overcomes EGFR inhibitor resistance. Methods Three EGFR wild type NSCLC cell lines H157, H460 and A549 were used to establish the xenograft nude mouse models of primary resistance to erlotinib and agent alone or combination of erlotinib and bevacizumab were used to treat mice in vivo. VEGF levels of these cell lines and human bronchial epithelial cell BEAS-2B (as a control cell line) were assayed in cell supernatant using ELISA. Erlotinib concentration in sera and tumor lysates of xenograft models were determined by High Performance Liquid Chromatography (HPLC). Results 1) VEGF level of H157 was higher than H460's and A549's was the lowest. 2) In vivo, bevacizumab inhibited tumor growth in H157, H460 and A549 models, and TGI (tumor growth inhibition, %) of A549 was relatively lower than the other two. 3) In H157 and H460 models but not A549 model, combination treatment was more effective than either agent alone. 4) Erlotinib concentrations of serum and tumor samples in combination group were higher in various degrees than erlotinib alone group depending on models. Conclusion Combined of EGFR and VEGFR blockades might enhance antitumor activity and angiogenesis inhibitor may modulate the tumor vasculature resulting in enhanced delivery of targeted agent to cancer cells depending on VEGF levels of cell lines in NSCLC.

IKUMI MATSUSHITA 1 , MINAKO HIJIKATA 1 , HIDEYUKI ITO 2 , NAOTO KEICHO 1 1 Department of Pathophysiology and Host Defense, Research Institute of Tuberculosis JATA, Japan, 2 National Center for Global Health and Medicine Hospital, Japan Background and Aim of Study Human beta defensin-1 is an antimicrobial peptide expressed in the airway epithelium without help of any inducers. Although many studies have shown that major polymorphisms of DEFB1 encoding the peptide are conserved and significantly associated with infectious and immune-related disorders, roles of DEFB1 in the pathogenesis are mostly unclear. Methods Expression levels of mRNA of DEFB1 were measured by real-time RT-PCR and their protein concentrations were determined by using ELISA. Transcriptional activities of cloned segments containing representative promoter haplotypes were determined in airway epithelial cell lines by using the Dual-Luciferase Reporter Assay System. Airway epithelial cells were stimulated with or without an analog of viral double-stranded RNA, polyinosinicpolycytidylic acid(poly IC).

Out of four extended DEFB1 haplotypes carrying three common polymorphisms in the 5'-untranslated regions, the -44G (rs1800972)-carrying haplotype showed overexpression of the baseline mRNA levels of DEFB1 in A549 cells and primary cultured cells. PolyIC stimulation significantly enhanced DEFB1 mRNA expression and increased DEFB1 protein concentrations and overrode transcription-promoting effect of the -44G haplotype. DEFB1 is generally thought to be constitutively expressed in human epithelial cells and some immune cells. In this study, we demonstrated that DEFB1 promoter genotype was associated with cellular gene expression and that DEFB1 expression was sensitive to exogenous stimuli such as polyIC irrespective of the genotype. Our data might provide insights into inconsistent results in previous disease association studies and the role for their genetic polymorphisms in the airway mucosa.

Background and Aim of Study Accumulating evidence indicates that cancer stem cells (CSCs) are involved in intrinsic resistance to cancer treatment. On the other hand, hypoxic microenvironment is an important stem cell niche, and promotes the persistence of CSCs in tumors. The aim of this study is to elucidate the role of hypoxia and CSCs in the resistance to gefitinib in non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation. Methods NSCLC cell lines, PC9 and HCC827, which express EGFR exon 19 deletion mutations, were exposed with high concentration of gefitinib under the normoxic or hypoxic condition. Seven days after gefitinb exposure, small fraction of viable cells could survive, and these cells were referred to as "gefitinib-resistant persisters" (GRPs). We performed quantitative real time polymerase chain reaction and immunofluoresence to evaluate the expressions of stemness genes and insulin-like growth factor 1 receptor (IGF1R)related factors. Results GRPs highly expressed stem cell genes including CD133 and Oct4, and showed the sphere-forming capacity in vitro and high tumorigenic potential in vivo. Expressions of IGF1R-related factors were upregulated and IGF1R was also phosphorylated on GRPs. Importantly, hypoxia promoted the activation of IGF1R on GRPs, and increased sphere-formation and the population of CD133-and Oct4-positive GRPs. Furthermore, knockdown of hypoxia inducible factor-1α(HIF-1α) reduced the number of GRPs with activated IGF1R. Finally, inhibition of IGF1R decreased the CD133-and Oct4-positive GRPs under the hypoxic condition. Conclusion Hypoxia increased the population of lung CSCs which were resistant to gefitinib in EGFR mutation-positive NSCLC through the activation of IGF1R.

Background Transforming growth factor β(TGFβ)-induced β-catenin translocation into cytoplasm is involved in epithelial-mesenchymal transition(EMT). In this congress, we also show that modulation of phosphorylation sites in the PTEN C-terminus (PTEN4A) inhibits TGFβ-induced EMT via blockade of β-catenin translocation. Nevertheless, how PTEN4A could exert the inhibitory effect on β-catenin translocation remains elusive. Aim of Study We aimed to illuminate the underlying mechanisms, by using several PTEN constructs with deletion mutants. Methods We prepared four deletion mutants, including 1) the PTEN C-terminus deletion, 2) the C 2 domain deletion, 3) the phosphatase domain deletion, or 4) both the C 2 domain and phosphatase domain deletion. Thus, we established lung cancer cells with a Dox-dependent gene expression system, in which these mutants were induced only when Dox is added. To evaluate the localization of β-catenin, immunofluorescence and confocal laser scanning microscopy were performed. Results Immunofluorescence images suggested that the PTEN C-terminus did not appear to directly inhibit TGFβ-induced β-catenin translocation into cytoplasm. We showed that both of the C 2 domain and the phosphatase domain might be essential to block the β-catenin translocation. Conclusions Inhibition of phosphorylation of the PTEN C-terminus, by which both of the C 2 domain and the phosphatase domain could retain the PTEN phosphatase activity, might blunt TGFβ-induced β-catenin translocation as well as EMT.

Inhaled corticosteroids are the most potent anti-inflammatory medications for the treatment of asthma. We have reported that corticosteroids have not only anti-inflammatory effects but also enhancement effect of airway epithelial barrier. However, the mechanism by which how corticosteroids enhance airway epithelial barrier function is not well understood. We therefore investigated the global gene expression analysis to identify candidate genes and signaling pathways involved in the enhancement of airway epithelial barrier. 16HBE, human airway epithelial cells were cultured on transwell inserts and exposed to dexamethasone (Dex) for 3 days to enhance barrier function. After measuring barrier function using Trans Electric Resistance (TER), we extracted total RNA from epithelial cells and performed microarray analysis. Gene networks were generated using Ingenuity Pathways Analysis to identify signaling pathways involved in airway epithelial barrier function. To determine steroid-inducible genes we identified involve in airway epithelial barrier function, we transfected 16HBE cells with small interfering RNA (siRNA) targeted to these genes, followed by TER measurements. We identified several steroid-inducible genes involved in processes associated with anti-apoptosis and wound healing on airway epithelial cells. Airway epithelial barrier function was reduced by knockdown of these genes. Our results indicate that steroid-inducible genes we identified can regulate the airway epithelial barrier function. These genes and signaling pathways might be new therapeutic targets for the vulnerability of airway epithelium of asthmatics. In acute lung injury (ALI), alveolar macrophages are one of the main sources of inflammatory cytokines. Macrophages are highly versatile cells and the local environment factors could shape their phenotypic and functional properties. It is necessary to understand the mechanisms involved in the progression of systemic inflammation and to design treatments to reduce the impact of ALI. The activated macrophages were classified into two groups, the classical activated macrophages (M1) and the alternative activated macrophages (M2). M2 macrophages express the mannose receptor, CD206. In this study we generated a line of transgenic mice expressing human diphtheria toxin (DT) receptor under the control of the CD206 gene promoter. In this transgenic mouse, DT induced systemic ablation of M2. In ALI model with LPS, inflammatory cytokines levels were higher in TG than WT. Histologically, ALI was exacerbated by ablation of M2. Alternative activated macrophages may play a protective role in the development of ALI.

Background and Aim of Study Pulmonary surfactant is a surface active lipoprotein formed by Alveolar type II cells, involved in preventing high altitude pulmonary edema. Induction of nuclear factor erythroid 2 p45-related factor (Nrf2) has been shown to decrease oxidative stress through the regulation of specific gene pathways. The association of Nrf2 and surfactant proteins (SP) under hypoxia is not well elucidated. Hence, the present study is aimed to determine the role of phase II antioxidant enzymes in enabling pulmonary surfactant homeostasis under hypoxia. Methods A549 cells were cultured under hypoxic environments (3%) for different time durations (1 h, 3 h, 6 h, 12 h, 24 h and 48 h). Male SD rats were exposed to hypobaric hypoxia (7620 m, 6 h). Results A549 cells exposed to different hours of hypoxia showed decrease in SP-A transcript expression from 3 h and remained constant though out the hypoxic exposures. Whereas, SP-B expression was decreased by 3 h and nearly abolished upon further exposures; while SP-C and SP-D expression was increased within 1 h of hypoxic exposure and remained constant till 48 h of hypoxic stress over control. The hypoxia exposure of A549 cells (6 h), showed a significant increase in protein and lipid oxidation along with reduced levels of GSH over control. The curcumin supplementation (10 μM) increased the expressions of Nrf-2 and HO-1 which might have enabled the cells in balanced expression of SPs along with reduced levels of oxidants. Our in vivo data also showed increased lipid peroxidation (p < 0.001) and protein oxidation (p < 0.05) in bronchoalveolar lavage fluid (BALF) which was significantly attenuated by curcumin administration (50 mg/Kg BW) 1 h prior to hypoxia exposure. The curcumin administration also resulted into decreased lung NFkB with increased expression of Nrf-2 and HO-1, followed by stabilised expression of HIF 1α. Conclusion Our results indicate that, curcumin facilitates the induction of phase II antioxidant enzymes promoting pulmonary surfactant homeostasis under hypoxia.

MOTOHIRO KIMURA, NAOZUMI HASHIMOTO, YOSHINORI HASEGAWA Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan Background and Aim of Study Although persistent TGF β stimulation induces epithelial-mesenchymal transition (EMT), significant increase in the phosphorylation level of the PTEN C-terminus is involved by TGFβ as well, resulting in the loss of PTEN activity. Although recently, we demonstrated that gene modulation of PTEN phosphorylation sites (PTEN4A) could inhibit phenotype changes through EMT in lung epithelial cells, by using the doxycycline (Dox)-inducible gene expression system in vitro, whether or not exogenous PTEN4A induction could exert the inhibitory effect against TGFβ-induced EMT remains elusive. Methods We evaluated whether or not exogenous PTEN4A induction could be effective on TGFβ-induced EMT in vitro, by establishing the adenovirus delivery system carrying PTEN4A. Results Both the naive cells and the cells transfected with adenovirus expressing GFP (control) treated with TGFβ showed the decreasing expression of E-cadherin and the de novo expression of fibronectin through EMT. In contrast, only the cells infected with adenovirus expressing PTEN4A kept the expression E-cadherin and inhibited the de novo expression of fibronectin against TGFβ treatment. Conclusions These data might propose therapeutic strategy to locally deliver the PTEN4A gene in disease models with TGFβ-induced EMT such as tumor or fibrosis.

Background and Aim Study It is well known that abnormal growth of pulmonary vascular smooth muscle cells (PASMCs) cause the pulmonary hypertension. To investigate the effect of mTOR siRNA loaded these nanomaterials on PASMCs proliferation and apoptosis induced by hypoxia. Methods Intracellular uptake study was performed by confocal laser scanning microscope. Cell transfection efficiency was evaluated by flow cytometry. PASMCs viability was analysed by MTT method. Cell apoptosis analysis was conducted using the Annexin V-FITC and propidiumiodide detection kit according to the manufacture's protocol. The mRNA expression of Bcl-xl was tested by two-step RT-PCR. The levels of Bcl-xl protein was determined by western blot.

Results mTOR siRNA loaded Ac-aCD/PEI nanoaystem could be efficiently transfected into rat PASMCs in dose-dependent manner, and take the inhibition effect on serum-induced cell proliferation. It could significantly suppress the expression of mTOR mRNA/protein, and enhance PASMCs apoptosis under hypoxia condition. Importantly, this data showed that Ac-aCD load mTOR siRNA could inhibit the hypoxia-induced the proliferation of PASMCs. Hypoxia and serum have no obviously effect on the cellular uptake of Ac-aCD/PEI1800 nanomaterials. Conclusion This pH-responsive hybrid nanosystem Ac-aCD can effectively load mTOR siRNA, which induce hypoxic PASMCs apoptosis and suppress the cell proliferation.

Background Disruption of alveolar-vascular barrier can be an early pathological change in ALI. Beta-adrenergic receptors (beta-ARs) play a critical role in the regulation of vascular endothelial barrier function in both normal and pathological conditions. It is known thatbeta-adrenergic receptor internalization are regulated by Rab5 GTPase in many cell types. However, the effects of Rab5 on the trafficking of beta-AR in pulmonary microvascular endothelial cells are poorly understood. Aim of the Study To investigate the effects of Rab5 on the endocytosis and cell-surface expression of beta-AR in pulmonary microvascular endothelial cells. Materials and Methods Rat pulmonary microvascular endothelial cells a(RPMVECs) were achieved by primary culture technology. Knockdown of Rab5 by siRNA and over-expression of Rab5 by transfecting with wild-type Rab5(Rab5WT) were performed in RPMVECs. Cell-surface expression of beta-ARs in RPMVECs was measured by intact cell ligand binding. Internalization of beta-ARs was measured by ligand internalization Assay. Downregulation of beta-ARs was measured by receptor down-regulation Assay. Sub-cellular distribution of beta2-AR was imaged by Fluorescent microscopy. Results We found that Rab5 siRNA strongly inhibited the agonist-induced internalization ofbeta2-AR and up-regulate the amount of beta-ARs on the cell surface in RPMVECs, whereas the wild-type Rab5(Rab5WT) promoted the agonist-induced internalization and down-regulation ofbeta2-AR but had a similar effects on the expression of beta-ARs on the cell surface. Conclusions We propose that Rab5 is essential for endocytosis and cellsurface expression ofbeta-ARs in PMVECs. Back Ground and Aim of Study Airway viral infection exacerbates asthma and chronic pulumonary obstructive disease (COPD). B7-H1/PD-L1 is a coinhibitory molecule implicated in an escape mechanism of viruses from the host immune systems. This escape may induce viral persistence and lead to exacerbation of the underlying diseases. We previously showed that an analog of viral double-strand RNA, polyinosinic-polycytidylic acid (poly IC), upregulated the expression of B7-H1/PD-L1 on airway epithelial cells, which was resistant to corticosteroid treatment. We investigated the effects of corticosteroid plus long-acting beta2-agonist (LABA) on the expression of B7-H1/PD-L1. We further investigated the additional effect of long-acting muscarinic agonist (LAMA) that is used as a standard therapy for COPD. Methods BEAS-2B airway epithelial cell line was stimulated with poly IC. The expression of B7-H1/PD-L1 was assessed by flow cytometry. Results Poly IC-induced upregulation of B7-H1/PD-L1 was suppressed by high-concentration ciclesonide but not by indacaterol. The upregulation was suppressed by low-concentration ciclesonide when used in combination with indacaterol. No additional effect of glycopyrrolate was observed on the expression of B7-H1/PD-L1. Conclusion Corticosteroid plus LABA attenuate virus-associated upregulation of B7-H1/PD-L1 on airway epithelial cells. This result may partly explain why the therapy with inhaled corticosteroid plus LABA prevents exacerbation of asthma and COPD.

Background and Aim of Study Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposure can influence COPD. The purpose of this study is to investigate clinical characteristics of COPD according to history of environmental exposure. Methods The study population comprised 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals that belong to the Korean Obstructive Lung Disease Study Group. We classified environmental exposure according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life questionnaire, exercise capacity, and CT phenotypes. Results Thirty-one subjects (8.9%) had history of living near factory, 271 (78.1%) had exposure history to briquette, and 184 (53.2%) had exposure history to firewood. There were no significant differences in clinical characteristics according to history of living near factory or exposure to briquette. However, subjects with history of firewood exposure had significantly longer duration of cough and sputum. Firewood exposure group showed higher FEV1 (1.27 L vs 1.16 L) and better exercise capacity (6 minute walk distance 707 m vs 492 m). Conclusion Clinical characteristics were not differed according to history of living near factory nor exposure to briquette. COPD subjects with exposure history of firewood had more frequent respiratory symptoms such as cough or sputum, while their pulmonary function and exercise capacity were preserved. Our data suggest that environmental exposure may influence clinical phenotype of COPD.

Global warming due to human activity lead to abnormal climate changes. Particularly strong impact of climate change has become evident in last decades, as in the industry developed cities of the world were fixed for long periods of smoke air (ex. Moscow -2010, Beijing -2011-12). Causes of these air pollutions were different factors, but the response of the respiratory system and the impact on public health were similar. Such air contamination in natural and industrial pollutants can cause pathological response from the respiratory tract. The aim of the study was to investigate the influence of air pollution due to forest fires amid to high air temperature on the morbidity respiratory dis- Epidemiologic studies have demonstrated that atmospheric contamination caused by Asian sand dust (ASD) storm aggravates asthma both in human adults and children. In the present study, two time-course studies (6 weeks and 14 weeks) were performed to investigate the adverse effects caused by ASD in experimental mice. CD-1 Mice were instilled with ASD samples intratracheally four or eight times at 2-week intervals with or without ovalbumin (OVA). In the case of the groups exposed eight times to ASD alone, alveolitis and bronchitis were exacerbated and various inflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF) increased. In the case of the groups co-exposed to ASD and OVA four times, allergic airway inflammation was aggravated. Proliferation of goblet cells in the airway epithelium along with Th2-cytokines such as IL-13 and eosinophil-relevant cytokine/ chemokines IL-5, Eotaxin and MCP-3 in BALF was also observed. A moderate fibrous thickening of the subepithelial layer in the airway was also observed pathologically in these groups. However, the eight-time co-exposure attenuated these changes. On the other hand, TGF-β1 and neutrophil number increased in BALF in the eight-time co-exposure groups compared with the four-time co-exposure groups. Adjuvant effects of ASD toward IgG1 and IgE production were recognized in the two time-course studies. However, the eight-time co-exposure did not reduce their productions. These results indicate that short-term sensitization of OVA with ASD aggravates allergic inflammation along with fibrous thickening of the subepithelial layer in the airway, whereas the long-term sensitization attenuates these changes, suggesting that suppressive immune responses are caused by TGF-β1-related immune tolerance.

Background Nontuberculous mycobacterial (NTM) lung diseases are generally managed as Mycobacterium avium complex (MAC). However, little is known about the clinical and radiographic differences between M avium and M intracellulare. This study examined the clinical characteristic and radiographic features in NTM lung disease. Methods Medical records of 113 patients that were given a new diagnosis of NTM lung disease from 1998 to 2013 were retrospectively reviewed. Results 78 patients (69%) had M avium lung disease, 32 patients (28%) had M intracellulare lung disease and 12 patients (11%) had others. 9 patients had lung disease of multiple species. M avium and M intracellulare are difference in the following clinical characteristics: age (64.6 ± 13.7 and 70.2 ± 12.4, p = 0.320), gender (M : F = 51:49 and M : F = 31:69, p = 0.084), receiving quinolone (3% and 15%, p = 0.026), having underlying disease (65% and 77%, p = 0.116), and radiographic features: having cavity (19% and 42%, p = 0.020) and spreading multiple lung lobes (2.6 and 3.0, p = 0.094). The patients with lung disease of multiple species do not have clinical and radiographic features compared to patients with lung disease single species of MAC. Conclusions M avium and M intracellulare have differences clinical and radiographic features. These differences may have implications for diagnosis, treatment and prognostication.

YASUAKI UEHARA 1,2 , SHIGERU ARIKI 1 , MOTOKO TAKAHASHI 1 , RINA TAKAMIYA 1 , YOSHIHIRO HASEGAWA 1,2 , HIROKI TAKAHASHI 2 , YOSHIO KUROKI 1 1 Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan, 2 

Human β-defensin 3 (hBD3) is a cationic antimicrobial peptide with broad spectrum microbicidal activity against both bacteria and fungi. However it also exhibits cytotoxicity against host cells in higher concentrations. In the previous study, we found that the cytotoxicity of hBD3 against lung epithelial cells was attenuated by pulmonary surfactant protein A (SP-A), a collectin implicated in host defense and regulation of inflammatory responses in the lung. Moreover, we identified that the functional region of SP-A lies within Tyr161-Lys201, tentatively called SP-A-derived peptide. In this study, we further characterized the effects of SP-A-derived peptide on cytotoxicity and antimicrobial activity of hBD3. SP-A-derived peptide significantly decreased membrane permeability of A549 cells treated with hBD3. In mice model, intratracheal instillation of hBD3 resulted in elevated LDH activity and the number of leukocytes in bronchoalveolar lavage fluid (BALF). Moreover, interstitial edema and alveolar septal thickening were seen in histological examination of hBD3 instilled mice. SP-A-derived peptide decreased both LDH activity and the number of leukocytes in BALF to the comparable level in BALF from control mice. The tissue damages were also dramatically improved in the presence of SP-A-derived peptide. To examine the effects of SP-A-derived peptide on the antimicrobial activity of hBD3, Staphylococcus aureus and Pseudomonas aeruginosa were incubated with hBD3 in the presence of SP-Aderived peptide. Antimicrobial activity of hBD3 against these microbes was not affected in the presence of SP-A-derived peptide at concentration sufficient to decrease cytotoxicity of hBD3. These results suggest that SP-A-derived peptide decreases cytotoxic activity of hBD3 without affecting its antimicrobial activity. Background and Aim of Study Chronic necrotizing pulmonary aspergillosis (CNPA), also called semi-invasive pulmonary aspergillosis, is an indolent and cavitary infectious process of the lung secondary to local invasion by Aspergillus species. We sometimes experience CNPA patients demonstrating acute progression of infiltrative shadow although few cases have been reported. In this study, we report two cases of acute exacerbation of CNPA examined pathologically after pneumonectomy. Methods We retrospectively reviewed medical records of two cases of CNPA demonstrating acute progression of in filtration prior to pneumonectomy. Result Case1: A 54-year-old man, with medical history of left upper lobectomy due to pulmonary tuberculosis 40 years previously, was diagnosed as pulmonary aspergillosis 4 years before admission based on a pulmonary cavity and positive Aspergillus antigen. Despite of administration of an antifungal drug and predonisolone, filtration in the left lower lung field emerged and deteriorated. An acute exacerbation of CNPA was suspected and residual left pneumonectomy was performed, pathologically revealing organizing pneumonia without evidence of fungus bodies. Case2: A 52-year-old man, with a medical history of pulmonary tuberculosis a long time before, was diagnosed as CNPA based on imaging findings and positive Aspergillus antibody. Although an antifungal agent was administered intravenously and locally, CNPA was uncontrollable with radiological deterioration. Left pneumonectomy was performed. Pathological findings of the resected lung included bronchocentric granulomatosis without evidence of invasion of fungi in the area of infiltrative shadow. Conclusion In CNPA cases, acute exacerbation with spread of infiltrative shadows was occasionally observed. We suspect that organizing pneumonia and granulomas detected in the area of infiltrative shadows may not be caused by fungal invasion but by allergic reaction to substances produced by Aspergillus.

YUMI TANAKA 1 , SHINJI MAEBEYA 1 , SHINYA TAMAKI 2 , TAKESHI SHONO 2 , HITOMMI TATSUTA 2 , TAKANOBU HOSO 2 , MICHIKO ARAKO 3 1 Department of Thoracic surgery, Wakayama Rosai Hospital, Wakayama, Japan, 2 Department of Respiratory Medicine, Wakayama Rosai Hospital, Wakayama, Japan, 3 Department of Internal Medicine, Saiseikai Wakayama Hospital, Japan

Background Surgical resection has always been regarded as standard treatment for pulmonary aspergilloma. However, surgery is not feasible in many cases due to the underlying disease such as low pulmonary function of the host. We report a case effectively treated with transbronchial intracavitary amphotericin B and whose cavity has been observed for 10 years by ultrathin bronchoscope. Case: Approximately 10 years before, a 45-year-old man was diagnosed with pulmonary aspergilloma. At first, he was treated by oral itraconazole for two months, since he refused the surgical resection. However, this had little effect and the hemosputum persisted. Therefore, weekly infusion of AMPH-B into the cavity by transbronchial route was performed 13 times. Moreover, we used fibrin glue mixed AMPH-B 15 times during six years. Results It was possible to observe chronologically the reduction and disappearance of the fungus ball through an ultrathin bronchoscope. Approximately three years have passed after the disappearance of his fungus ball, he remains alive without evidence of recurrence. Conclusion The transbronchoscopic infusion of AMPH-B into the cavity is thought to be safe and effective in patients with pulmonary aspergilloma. To the best of our knowledge, this is a rare case of pulmonary aspergilloma followed in the long term by ultrathin bronchoscope.

Pulmonary Mycobacterium avium complex (MAC) disease has a prolonged course of infection and is often associated with bronchiectasis or cavitary disease. Various pathogenic microorganisms are often infected or colonized in patients with bronchiectasis. This study aimed to identify prevalence of co-infection with other pathogens than MAC and risk factors for the co-infection in patients with pulmonary MAC disease. Methods We retrospectively analyzed 221 pulmonary MAC patients fulfilling the 2007 ATS diagnostic criteria who visited Kyoto University Hospital from January January 2001 to December 2012. We reviewed patient characteristics, microbiological results and chest computed tomography findings from medical records. We defined chronic pathogenic co-infection that potential pathogens other than MAC had been isolated from consecutive sputum samples taken on more than two visits >3 months apart. Introduction Treatment for pulmonary aspergillosis has been a challenging issue. Despite the introduction and use of recently approved antifungal treatments, treatment for pulmonary aspergillosis remains to be difficult. Sometimes, surgical treatment is required. In this study, the pulmonary aspergillosis cases with surgical treatment were surveyed in our institute. Method Pulmonary aspergillosis patients who received the surgical treatment were analyzed retrospectively. The data were collected from medical records. Results The total cases were nine, five female and four male. Median age was 64 years old. As symptoms of pulmonary aspergillosis, four patients had hemoptysis/hemosputa, one cough, one sputum, and four asymptomatic. As an underlying disease, two patients had bullae, one diabetes mellitus, one COPD, one after lung transplantation, and four without an underlying disease. Serum beta-D-glucan was negative in all cases. Aspergillus antigen test showed positive results in four patients. Antifungal agents were not used before surgical treatment. Whereas, antifungal drug was used after surgical resection in five cases, two VRCZ, one L-AMB, one MCFG, and one ITCZ. The severe complications accompanying a surgical treatment have not been experienced. All patients had been doing well one month after surgery. Conclusion Surgical treatment for pulmonary aspergillosis could be carried out without serious complication and demonstrated good postoperative course in selected cases. Background Syndecan-4 is a transmembrane heparan sulfate proteoglycan which is expressed in a variety of cells such as epithelial cells and neutrophils. Heparan sulfate glycosaminoglycan side chains of syndecan-4 have been reported to bind to several proteins such as growth factors and cytokines suggesting to have various biological roles. We have reported that syndecan-4 limits the extent of pulmonary inflammation and lung injury in murine LPSinduced lung inflammation model (Tanino Y, et al. Am J Respir Cell Mol Biol, 2012). The goal of this study was to clarify the role of syndecan-4 on acute pneumonia. Methods Syndecan-4 in serum was first measured in patients with acute pneumonia and compared with healthy volunteers. Next, the relationship between syndecan-4 in serum and clinical parameters was analyzed. At last, survival rate was compared between wild-type and syndecan-4 deficient mice after intranasal instillation of S. pneumoniae. Results In patients with acute pneumonia, syndecan-4 in serum was significantly higher compared with healthy volunteers, and had a negative correlation with pneumonia severity score. In addition, serum syndecan-4 on admission was higher in patients who improved in short term antibiotic therapy compared with those who required long term antibiotic therapy. Moreover, serum syndecan-4 gradually increased during therapy in patients who had improved in a short term antibiotic therapy in contrast to the stable levels of serum syndecan-4 in patients who had required long term antibiotic therapy. Furthermore, survival rate of syndecan-4 deficient mice was significant worse compared with wild-type mice. Conclusions Syndecan-4 regulates pulmonary inflammation, and could be a useful biomarker in patients with acute pneumonia. Lysophosphatidylcholine (LPC) is a novel inflammatory lipid mediators, which has been suggested as an important biomarker to predict sepsis related mortality. Previous studies showed that decreased LPC concentration is associated with sepsis related mortality. So, we investigated serum LPC level in community acquired pneumonia to predict outcome and analyzed correlations between serum concentration and clinical parameters. We prospectively collected blood samples from patients who were diagnosed of community acquired pneumonia in Pusan national university yangsan hospital from August 2011 to February 2013. All blood samples were obtained initially (D1) and 7 day (D7) after. Obtained samples were immediately centrifuged and plasma was stored at −80 degree Celcius within 2 hour. We checked plasma LPC levels using ANZWELL LPC Assay Kit (Alfresa Pharma Corporation, Japan) which is an commercial enzymatic assay kit. We retrospectively reviewed medical records of patients and analyzed correlations between plasma LPC levels and clinical parameters such as pneumonia severity index (PSI), CURB65, simplified acute physiology score II (SAPS II). Forty five patients with community acquired pneumonia were included in this study. The mean PSI, CURB65 and SAPS II were 96.27 ± 41.374, 1.78 ± 1.363 and 34.47 ± 21.288, respectively. The mean serum LPC concentrations at day 1 and day 7 were 57.88 ± 43.42 umol/L and 72.60 ± 58.04 umol/L, respectively. The serum LPC concentration at D7 was significantly lower in non-survivor group (16.07 ± 30.83 umol/L vs 92.39 ± 52.15 umol/L, p < 0.05) even though the concentration at D1 did not differ between survivors and non-survivors. The serum LPC concentration at D7 were significantly correlated with PSI (R = −0.444, p < 0.05), CURB 65(R = −0.586, p < 0.01) and SAPS II(R = −0.576, p < 0.01), respectively. The LPC concentration at D7 correlated with clinical parameters of community acquired pneumonia. Persistently decreased concentration of LPC was significantly associated with mortality of community acquired pneumonia. Background and Aim of Study A significant human pathogenic bacterium, Streptococcus pneumoniae was recognized as a major cause of pneumonia, and is the subject of many humoral immunity studies. Diagnosis is generally made based on clinical suspicion along with a positive culture from a sample from virtually any place in the body. But the testing time is too long, this study is to establish a rapid diagnosis method to Identification of Streptococcus pneumonia. Methods Our laboratory has recently developed a new platform called RealAmp, which combines loop-mediated isothermal amplification (LAMP) with a portable tube scanner real-time isothermal instrument for the rapid detection of Streptococcus pneumonia. Three pairs of amplification primers required for this method were derived from a conserved DNA sequence unique to the Streptococcus pneumonia. The amplification was carried out at 63 degree Celsius using SYBR Green for 40 minutes with the tube scanner set to collect fluorescence signals at 1-minute intervals. Clinical samples of Streptococcus pneumonia and other bacteria were used to determine the sensitivity and specificity of the primers by comparing with an 18S ribosomal RNA-based nested PCR as the gold standard.

The new set of primers consistently detected laboratory-maintained isolates of Streptococcus pneumoniae from our hospital. The new primers also proved to be more sensitive than the published species-specific primers specifically developed for the LAMP PHOSPHATE IN A JAPANESE PHASE I STUDY   TOSHIAKI TANAKA 1 , YUKO HAYASHI 1 , KAZUHITO OKUMURA 1 ,  KENICHI YOSHIKAWA 1 , TETSUSHI KOMORI 2 , KUMIKO T KANATANI 3 ,  IPPEI IKUSHIMA Background Tedizolid phosphate (TZP) is a novel antibiotic for infections due to Gram-positive pathogens, including MRSA. The current study investigated the safety and tolerability of TZP in Japanese healthy subjects for its clinical development for nosocomial pneumonia (and skin and soft tissue infection). Methods Japanese healthy male subjects (N = 36) received TZP intravenously (IV) over 60 min as a single infusion of 50 mg in step 1 (n = 9) and 100 mg in step 2 (n = 9), or placebo (n = 3 in each step). In step 3, subjects received TZP orally (PO; 200 mg n = 8, or placebo n = 4), or IV (200 mg n = 8, or placebo n = 4) in a two-way cross-over design. Safety investigations included assessment of adverse events (AEs), vital signs, ECG parameters, and laboratory tests. Results A total of 3 out of 26 subjects (11.5%) receiving IV TZP experienced AEs: 1 out of 9 subjects (11.1%) in step 2 and 2 out of 8 subjects (25%) in step 3. One out of all 10 subjects (10%) receiving IV placebo solution experienced an AE (i.e. laboratory changes). Only one drug-related AE (3.8%, 1 out of 26 subjects) occurred in a subject receiving IV TZP 200 mg. In this subject, TZP administration was discontinued permanently and the AE (i.e. allergic rash) resolved after appropriate treatment. No AE occurred in subjects receiving IV TZP 50 mg, PO TZP 200 mg, or PO placebo. There were no serious AEs reported in any group. There were no clinically significant changes in vital signs, ECG parameters, and laboratory evaluations after TZP administration. Conclusion Single-dose administration of TZP (50, 100 or 200 mg, both IV and PO) was well-tolerated in Japanese healthy male subjects. Background Tedizolid phosphate (TZP) is a novel antibiotic currently under clinical development (phase III) for the treatment of nosocomial pneumonia and has successfully completed two global phase III studies for acute bacterial skin and soft tissue infections (ABSSSI). The current phase I study investigated the safety and tolerability of TZP in Japanese healthy male subjects to support its development for nosocomial pneumonia and skin and soft tissue infection in Japan. Methods Twenty four subjects were randomised to receive TZP 200 mg or placebo once daily for 7 days, either intravenously (IV) over 60 minutes or orally [cohort 1 (IV): TZP n = 8 and placebo n = 4, cohort 2 (oral): TZP n = 8 and placebo n = 4]. Subjects were followed up for further 9 days. Safety investigations included assessment of adverse events (AEs), vital signs, ECG parameters, ophthalmologic examination, and laboratory tests. Results Nine (37.5%) of 24 subjects experienced AEs (8 subjects receiving TZP in cohort 1 and 1 subject receiving placebo in cohort 2). All 9 subjects reported at least 1 drug-related AE. There were no serious AEs reported in any group. In cohort 1, the most frequently reported drug-related AEs were injection site paraesthesia (75.0%, 6 out of 8) and injection site pain (25.0%, 2 out of 8) in subjects receiving TZP; all were mild in severity. In cohort 2, atrial fibrillation occurred at moderate severity in one subject receiving placebo and was deemed by the investigator as a drug-related AE; placebo administration was discontinued in this subject. No clinically significant changes were found in laboratory evaluations, vital signs, ECG parameters, ophthalmologic examination, and physical examinations in this study. Conclusions Tedizolid phosphate (both IV and oral) was well-tolerated in Japanese healthy male subjects during the 7-day administration and the follow-up period.

Background Asthma is now well recognized to be a heterogeneous disease, but no studies have been involved into mast cell (MC)-based phenotypes of asthma in induced sputum. Methods Induced sputum samples were collected from healthy subjects (n = 16) and adults with stable asthma (n = 55). Inflammatory cell counts and whole-genome gene expression microarrays in induced sputum were analyzed. MC phenotypes in induced sputum were classified according to MC biomarkers (tryptase, chymase and carboxypeptidase [CPA3]). Differential genes over MC phenotypes were validated by qPCR. Results Non-MC (n = 18), MCTC (n = 29) and MCT (n = 18) phenotypes were successfully identified, which was based on whether the mRNA expression of tryptase, chymase, or CPA3, was present in microarrays analysis of induced sputum at P < 0.01 detection value. In MCTC subtype, although it had similar demographic and medical characteristics in comparison with non-MC and MCT subtypes, there was an increase in FENO, eosinophil counts and proportion in induced sputum, bronchial sensitivity and reactivity, and worsening asthma control level (all P < 0.05), which would result from differential gene expression profiling such as TPSAB1, CPA3, CD1A, CD1B, CD1C, CEBPE, CLC, CLEC4F, DNASE1L3, GPR56, HDC and LTC4S. Furthermore, it had a higher proportion of MCTC subtype in eosinophilic asthma (EA) than other cellular inflammation phenotypes (x2 = 22.41, P = 0.001). Although eosinophil proportion and counts in induced sputum were associated with both tryptase (r = 0.57, P < 0.001; r = 0.57, P < 0.001, respectively) and CPA3 (r = 0.68, P < 0.001; r = 0.65, P < 0.001, respectively), multivariable logistic regression model indicated that only CPA3 (OR = 6.04, 95% confidence interval = [1.10, 32.97], P = 0.038) but not trptase (OR = 0.18, 95%CI = [0.02, 1.72], P = 0.137) contributed to EA. Conclusion MC-based phenotypes of asthma in induced sputum have been established, in which MCTC phenotype played an important role in the underlying pathobiology of EA. Targeted MCTC would be a promising approach for treating EA.

We studied lung sounds in sixtyeight cases with asthma and tried to describe breath sounds objectively, i.e., numerically. We divided lung sounds into vesicular (V, n = 43), vesicular/broncho-vesicular (V/BV, n = 6), bronchovesicular (BV, n = 14) and bronchial (B, n = 5) sounds by auscultatory findings. We measured expiratory/inspiratory (E/I) sound power ratio, highest frequency of inspiratory (HFI) and expiratory (HFE) sounds. Both sound power and sound frequency correlated well with auscultatory findings. E/I power ratio for V, V/BV, BV and B were 0.27 +/− 0.16 (mean +/− S.D.), 0.39 +/− 0.23, 0.49 +/− 0.40 and 0.72 +/− 0.55. HFE for V, V/BV, BV and B were 252 +/− 57.2 (Hz), 281 +/− 21.9, 410 +/− 21.9 and 472 +/− 68.6. HFI for V, V/BV, BV and B were 421 +/− 96.6, 443 +/− 60.9, 571 +/− 110.1 and 492 +/− 70.0. In subjects without wheezing (n = 60), E/I, HFE, and HFI were 0.34 +/− 0.032 (mean+/− SE), 293 +/− 12.9, and 460 +/− 15, respectively. In subjects who had wheezes (n = 8), E/I, HFE, and HFI were 0.43 +/− 0.077, 404 +/− 41.8, and 515 +/− 39. Breath sounds of patients with wheezes showed higher HFE, HFI and E/I than those of without wheezes. In subjects who did not have rhonchi (n = 58), E/I, HFE, and HFI were 0.35 +/− 0.047, 305 +/− 14.7, and 462 +/− 15.9. In subjects who had rumbling rhonchi (n = 10), E/I, HFE, and HFI were 0.33 +/− 0.089, 312 +/− 31.8, and 485 +/− 30.5. Basic breath sounds in wheezing patients were bronchial while those of non-wheezing patients were vesicular. Basic breath sounds were not different between patients with or without rumbling rhonchi. We conclude that numerical description of vesicular and bronchial breath sounds was possible. This sound analysis revealed that basic breath sounds of wheezing patients were bronchial breath sounds. THE DIFFERENT SUPRESSIVE CAPACITY OF REGULATORY T  CELLS ON TH1 AND TH2 CELLS IN PATIENTS WITH  ASTHMA ATTACK   JING LIU, JINZHI YIN, KE WANG, Objective To study the different supressive capacity of regulatory T cells (Tregs) on Th1 and Th2 cells in patients with asthma attack. Methods Recruited asthmatic patients (n = 30) and healthy control (n = 30), collected peripheral venous blood from healthy control and asthmatic patients in attack stage and stable stage respectively, and then isolated CD4+CD25+ CD127-/low Tregs and CD4+CD25-effect cells with immunomagnetic beads method (purity was above 90%). The effect cells were cultured with PHA stimulation with or without Tregs. Measured the proliferation (3H-Thymidine), expression of T-bet and GATA3 (RT-PCR), production of IFNr and IL-13 (LUMNEX) in effect cells with or without Tregs intervention. Analyzed the supressive capacity of Tregs on Th1 and Th2 cells in asthmatic patients in attack stage and stable stage, comparing with control group. Results Tregs could suppress the proliferation of effect cells in both asthmatic and healthy groups, and the suppressive capacity of Tregs in patients with asthma attack decreased significantly when compared with healthy group (P = 0.003), but there was no significant decline in stable asthma (P = 0.07). The suppressive capacity of Tregs to the expression of GATA-3 and production of IL-13 in patients with asthma attack was less effective than in healthy group, but the suppressive capacity to the expression of T-bet and production of IFN-r in asthma attack did not decrease. The supressive capacity of Tregs in asthmatic patients in stable stage was modified in some degree, compared with asthma attack. Conclusion There was deficiency for the suppressive capacity of Tregs on effect cells proliferation and Th2 cells function in asthma attack, but this deficiency was modified in some degree in stable asthma. The deficiency for the suppressive capacity of Tregs to Th2 but not Th1 cells may indicate the Th2-polarization in asthma development. Key Words Tregs, Th2 cells, asthma attack, suppressive capacity. Objective To investigate the situation of adult asthma control and management in Jilin province. Methods Telephone interviewed with adult patients with moderate to severe asthma, who were discharged from the Second hospiatl of Jilin University from 2009-2011. 963 patients out of 1260 visited had finished the questionare by telephone. The questionnaire included possible risk factors such as age, sex, population group, area of residence, occupation, and income, the number of hospital and emergency room admissions in the next year followed dischargement from the Second Hospiatl of Jilin University, the education of physicians to patients, the partnership between physicians and patients, the understanding to GINA and using LABA/ICS in patients. Areas of residence were categorised as urban or rural. Results 1. Most physicians (95.4%) in emergency, general medicine and respiratory medicine could educate and treatment asthmatic patients based on GINA, when patients were in hospital, but the follow up rate of patients was low (18.6%). 2. The adult asthma control in Jilin province was poor, the rate of hospital and emergency room admissions within one year after dischargement was high to 35.8%. 3. The risk factors to hospital and emergency room admissions within one year after dischargement were female, older than 60, income per month less than 1000 RMB, elementary school or lower education level, rural residence, do not use LABA/ICS regularly, do not keep in touch closely with doctors after dischagement (odds ratio (OR) were respectively 3.1, 7.4, 6.4, 4.7, 8.8, 2.4, 3.2). 4. Compared with urban residence, adult asthma control was worser than that in rural residence. Conclusion The adult asthma control in Jilin province was poor, specially in rural residence, which may due to partly lower economic and educational level in our province. Key Words adult asthma control, Jilin province, rural residence. Background A high prevalence of exercise-induced bronchoconstriction (EIB) can be found in elite athletes, but the underlying mechanisms remain elusive. Methods Airway responsiveness, NGF and EPI levels, and chromaffin cell structure in high/moderate -intensity training (HiTr/MoTr) rats with or without ovalbumin sensitization were measured in a total of 120 SD male rats. The expression of NGF-associated genes in rat adrenal medulla was tested. Results Both HiTr and OVA intervention significantly increased airway resistance to aerosolized methacholine measured by whole-body plethysmography. HiTr significantly increased inflammatory reaction in the lung with a major increase in peribronchial lymphocyte infiltration, whereas OVA significantly increased the infiltration of various inflammatory cells with an over 10-fold increase in eosinophil level in bronchoalveolar lavage. Both HiTr-and OVAintervention up-regulated circulating NGF level and peripherin level in adrenal medulla, but down-regulated phenylethanolamine N-methyl transferase level in adrenal medulla and circulating EPI level. HiTr+OVA and HiTr+ExhEx (exhaustive exercise) interventions significantly enhanced most of the HiTr effects. The elevated NGF level was significantly associated with neuronal conversion of adrenal medulla chromaffin cells (AMCC). The levels of p-Erk1/2, JMJD3, and Mash1 were significantly increased, but the levels of p-p38 and p-JNK were significantly decreased in adrenal medulla in HiTr and OVA rats. Injection of NGF antiserum and moderate-intensity training reversed these changes observed in HiTr and/or OVA rats. Conclusion Our study suggests that NGF may play a vital role in the pathogenesis of EIB by inducing neuron transdifferentiation of AMCC via MAPK pathways and subsequently decreasing circulating EPI.

BULKIS NATSIR, FAISAL YUNUS, BUDHI ANTARIKSA, TRIYA DAMAYANTI Departement of Pulmonology and Respiratory Medicine, University Indonesia, Jakarta, Indonesia Background and Aim of the Study Many patients have asthma that is inadequately controlled which is a cause of frequent emergency department (ED) visits and hospital admissions. Improper inhaler device technique is most likely one of the major causes associated with uncontrolled asthma. Our objectives were to evaluate the inhaler techniques among asthmatic patients, and its relationship with asthma control and ED visits, also to investigate factors associated with improper use of inhaler devices. Methods A cross-sectional study was done on all the patients who visited asthma clinic at Persahabatan Hospital in June 2013 with the diagnosis of bronchial asthma and used steroid inhaler as a controller. Data was collect on demography, severity of asthma and asthma management. We assessed the inhaler techniques for each patient using an inhaler technique checklist based on Global Initiative for Asthma. Results A total of 60 asthma patients were included in the study. Of these, 16 (39.1%) were males with a mean age of 51.00 ± 14.35 years, and 44 (77.3 %) were females with a mean age 51.73 ± 14.09. Improper use of asthma inhaler devices was observed in 36 (60%) of the patients and was associated with level of formal education (p = 0.016), irregular clinic follow-ups (p = 0.01), uncontrolled asthma ACT (score < 15) (p = 0.04), ED visits (p = 0.00). Multiple logistic regression analysis revealed that a lack of regular follow-ups (p = 0.03) and level of education (p = 0.043) were more likely to lead to the improper use of an asthma inhaler device. Conclusion Improper asthma inhaler device use is associated with level education, irregular clinic follow ups, poor asthma control and ED visits. We suggest a prospective analytic study for determining the risk factors that can lead to improper asthma inhaler technique. IN ASTHMA EXACERBATION   NAOYA TAKEDA, AKIRA MATSUI, AYAKO MIYAZAWA, TOSHIYUKI KATOH  Department of Respiratory Medicine and Allergology, Kariya Toyota General  Hospital, Aichi, Japan Background Obesity is a risk factor for developing asthma. Adipokines has also been shown to increase airway inflammation and hyper responsiveness. However, little is known the role of adipokines in asthma exacerbation. Objectives The purpose of this study is to evaluate the effect of adipokines in asthma exacerbation. Methods This study enrolled 20 hospitalized patients with acute exacerbation, 43 stable patients with mild to moderate asthma and 10 normal subjects for comparison. Serum leptin and adiponectin levels were evaluated before and after treatment with systemic corticosteroids. Results The serum adiponectin level differed significantly among the acute exacerbation patients (9.2 ± 6.6 μg/ml), stable asthmatics (10.6 ± 6.0 μg/ml), and normal subjects (7.5 ± 3.5 μg/ml). Moreover, serum adiponectin level in hospitalized patients after treatment (10.1 ± 6.7 μg/ml) was increased significantly. However, there were no difference in serum leptin level among the acute exacerbation patients before (11.8 ± 9.5 ng/ml) and after treatment (10.5 ± 6.2 ng/ml), stable asthmatics (10.8 ± 11.0 ng/ml), and normal subjects (9.6 ± 7.7 ng/ml). Conclusion Decrease in serum adiponectin level may be associated with acute exacerbation of asthma. It may be considered as one of mechanism of refractory asthma in obese subjects. Background One out of 10 Filipino children suffer from bronchial asthma. Its increasing prevalence worldwide over the past decades causes significant morbidity to the patients and their families when uncontrolled. In developing countries, the form of medicine, cost and access to medications are significant factors in achieving good control of symptoms. This study aimed to determine if the use of low dose oral corticosteroid is a safe and effective alternative treatment for children with persistent asthma. Methods Forty patients, 6 to 15 years old, with newly diagnosed moderate persistent asthma were randomized into two groups. For 3 months, the control group received inhaled corticosteroid (budesonide) at 200 mcg twice daily while treatment group received a single morning dose oral cosrticosteroid (prednisone) at 0.5 mg/kg (maximum dose: 10 mg/day). Efficacy was assessed based on daytime and nighttime coughing, limitation of activity, use of bronchodilators, FEV1, PEFR and level of asthma control. Safety parameters evaluated were blood pressure, pre and posttreatment determination of serum cortisol and fasting blood sugar levels. Results Study participants from both groups showed comparable improvement in daytime and nighttime cough, need for bronchodilators and limitation of activity. PEFR is the only parameter that showed a significant difference, participants under the inhaled corticosteroid group showed lower PEFR values than the oral corticosteroid group throughout the entire study period. There was no significant difference in their FEV1 but basically had the same trend as that of the PEFR. There was no significant difference in the safety parameters evaluated. Study participants from both groups showed a decrease in cortisol levels after 3 months of treatment but none had signs and symptoms of adrenal insufficiency. Conclusion There was no significant difference in the safety and efficacy of oral versus inhaled corticosteroid in the treatment of children with moderate persistent asthma after 3 months of treatment.

The transfer of care of paediatric asthma patients to adult hospitals is usually done at approximately 18 years of age. Currently, no structured transition program exists. The aim of this study was to evaluate the quality of life and experiences of high-risk asthma patients transferred from paediatric to adult care. Methods A cross sectional questionnaire survery of 36 high-risk asthma patients whose care was transferred from KKH to the adult hospitals between 2004 to 2011, was done. The self administered Asthma Quality of Life Questionnaire (Standardised) [AQLQ(S)] was used to assess the quality of life. Results 20 patients (56% response rate) returned the completed questionnaire and the AQLQ(S). The median (IQR) AQLQ(S) score was 193 (164-210). 75% of the participants felt that they were transferred to the adult service/ hospital at the appropriate age. 80% of the subjects stated that they were given sufficient information/guidance about the transfer of care and knew what to expect from the adult service. None of the respondents faced any challenges/ difficulties in the transfer of care process. Suggestions for improvement by the respondents included the need for (a) a detailed transfer medical report to the receiving physician, (b) better continuity of care and (c) improved communication at various levels. Conclusion Asthma patients transferred from KKH to the adult hospitals continue to enjoy good quality of life. The results of this study highlight the need for well coordinated and robust transition of care arrangements for improving the quality of care for adolescents with chronic illnesses. Background and Aim of Study Fluticasone furoate (FF), a once-daily inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting beta2 agonist (LABA), are in development as a once-daily (OD) combination therapy for asthma. We assessed efficacy and safety of OD FF/VI, compared with twicedaily (BD) fluticasone propionate (FP), in patients of Asian ancestry. Methods This was a randomised, double-blind, double-dummy, parallelgroup study. Eligible patients using stable high-dose ICS or mid-dose ICS/ LABA for >= 4 weeks before screening and ICS alone during run-in were randomised (1:1) to receive FF/VI 200/25 mcg OD or FP 500 mcg BD for 12 weeks. Primary endpoint: change from baseline in daily evening peak expiratory flow (PEF) averaged over the 12-week treatment period. Safety endpoints included adverse events (AEs), vital signs, ECG and laboratory evaluations. Results The ITT population comprised 309 patients (mean age 47.9 years, 59% female); 255 completed the study. FF/VI produced significantly greater improvement from baseline evening PEF than FP (+28.5 L/min [95% CI: 20.1, 36.9]; p < 0.001). Statistically and clinically significant treatment differentiation was apparent at Week 1 and was maintained. The incidence of AEs overall were similar between groups (FF/VI 26%; FP 27%). The incidence of drug-related AEs was 3% in both groups; the most common drug-related AE was oropharyngeal pain (FF/VI 2%; FP < 1%). Three patients (1 FF/VI; 2 FP) reported a total of five serious AEs and all were withdrawn. There were no clinically significant changes in vital signs, 12-lead ECG parameters or laboratory evaluations. Conclusion Once-daily FF/VI 200/25 mcg demonstrated clinically and statistically significant improvements in lung function compared with FP 500 mcg BD in patients of Asian ancestry, apparent from Week 1 and maintained over 12 weeks. No safety issues of clinical concern were identified with either treatment. Findings were consistent with previous observations in a mixedethnicity population (O'Byrne PM, ERS 2012). Funding GlaxoSmithKline (HZA113714,NCT01498653). Background Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. With appropriate treatment then the clinical manifestations of asthma can be controlled. The association between airway inflammation and asthma control level is not clear at present. The study was conducted to explore the relationship between inflammatory cells on sputum induction and asthma control level as determined by the Asthma Control Test (ACT). Methods This is a cross sectional analytic study with consecutive sampling that was conducted in the asthma outpatient clinic Dr Soetomo Teaching Hospital, Surabaya, Indonesia. All participants were stable asthma patients who met the inclusion and exclusion criteria. Results Data from 30 patients were analyzed (well controlled = 10, not well controlled = 8, uncontrolled = 12) with the percentage of eosinophils was 33.58 ± 8.76, basophils 3.92 ± 2.74, neutrophils 19.73 ± 8.44, lymphocytes 26.87 ± 9.66, monocytes 15.90 ± 5.79, and total cells count 39.60 ± 10.47 × 102/ml. There was no significant correlation between inflammatory cells on sputum induction and ACT total scores (p > 0.05). Conclusion Inflammatory cells on induced sputum examination can not be used as a parameter to determine the level of asthma control and vice versa. Keywords asthma, inflammatory cells on induced sputum, asthma control level. Results The incidence of severe exacerbations with FP/FORM was 3.0% (95% CI 1.4, 4.5) in Study 1 and 2.9% (95% CI 0.9, 4.8) in Study 2; the pooled incidence was 2.9% (95% CI 1.7, 4.1). The reported incidences of exacerbations for FP/salmeterol (SAL) and budesonide (BUD)/FORM were 9.1-13.7% and 8.8-15.3%, respectively, and 2.9-29.5% for free combinations of FP, BUD or beclometasone and a LABA. Conclusions Long-term FP/FORM therapy was associated with low rates of severe exacerbations in 2 distinct studies and populations; this incidence compares favourably with those from long-term studies of FP/SAL and BUD/FORM, and with free combinations of an ICS and a LABA. These data support the utility of FP/FORM in reducing the incidence of asthma exacerbations. (Table) . The incidence and annualized rate of any exacerbation was significantly lower with FP/FORM. Conclusions FP/FORM significantly improves lung function and asthma control measures, and is associated with a lower incidence of exacerbations compared with FP. Background and Aim of Study The efficacy of omalizumab, an anti-IgE antibody, has been studied in patients with severe bronchial asthma. It has been reported that omalizumab was unable to improve objective results; however, improvements were seen for subjective symptoms in asthmatic patients. The aim of this study is to evaluate the efficacy of omalizumab as a long-term disease therapy in severe and persistent asthmaic patients assessed by pulmonary function tests, AHQ scores, ACT scores, number of emergency visits and the dosage of methylprednisolone. Methods Omalizumab was administered subcutaneously every 2 or 4 weeks based on serum IgE levels and body weight in patients. Pulmonary function tests, AHQ, ACT, number of emergency visits and dosage of methylprednisolone during the 12-month period were compared with the previous year. Results Ten patients were enrolled. Treatment with omalizumab yielded no improves for lung function; however, the number of emergency visits (19.3 to 1.2, p = 0.020) and dosage of methylprednisolone (871.5 mg to 119.0 mg, p = 0.046) showed significant reductions when compared to the previous year. AHQ and ACT at 16 weeks improved significantly compared to study baseline but after week 20, no significant improvement was noted. Conclusion Omalizumab significantly reduced the number of emergency visits and methylprednisolone usage. AHQ and ACT were considered useful in the assessment of subjective symptoms in asthmaic patients. Background and Aim of Study Recent progress has been made in understanding the link between innate and adaptive immunity in asthma. We have previously reported that a distinct sensitization pattern was associated with thymic stromal lymphopoietin (TSLP) gentype. The aim of this study is to identify the characteristics of asthma phenotypes determined by a cluster analysis of IgE responsiveness and the relationship between asthma phenotypes and TSLP genotypes. Methods We studied 263 adults' patients of asthma from Ibaraki, a prefecture in central Japan and 31 adults from Kamishihoro, a cedar-free, birchdominant town in northern Japan. Levels of total serum IgE and specific IgE antibodies towards 14 major inhaled allergens were measured. With the use of these measures, cluster analysis was applied to classify the phenotypes of adult asthma. We also examined the genetic effects of 2 TSLP functional single nucleotide polymorphism (SNPs) on the development of each asthma phenotype using multinomial logistic regression analysis. 3 University of Aberdeen, Aberdeen, UK Background and Aim of Study Patient attitudes towards asthma vary and this may impact on disease management. This analysis was designed to group respondents to a large European survey into clusters based on their attitudes towards asthma and its management. Methods Online surveys were completed by 8000 patients with asthma (aged 18-50 years, ≥2 prescriptions in the last 2 years) from 11 countries. Cluster analysis was used to identify different clusters of patients based on attitudes towards asthma. Results Four different clusters were identified. Clusters 1 and 2 were defined by a high level of confidence in managing their asthma, and low levels of concern about the disease. Cluster 1 was more adherent to therapy and less likely to ignore HCP instructions than Cluster 2. Clusters 3 and 4 were more concerned about their asthma and considered it serious, and wanted to improve their disease management; these clusters had the lowest levels of GINA-defined control. Cluster 4 was less adherent to therapy and more likely to ignore HCP instructions than Cluster 3. Cluster 4 was most likely to seek additional information about asthma. Conclusion This survey identifies four distinct clusters of patients with asthma that differ in attitude, adherence and educational need. Understanding these differences may facilitate the development of appropriate asthma management strategies.

Cluster 1(n = 2027); Cluster 2(n = 1812); Cluster 3(n = 1496); Cluster 4(n = Introduction Asthma audit in 2007 found that asthma management in Thailand was suboptimal. Assessment of asthma severity and asthma control was mainly on symptoms. Peak expiratory flow was measured in only 1.08% of asthma visited in out-patient clinic. Inhaled corticosteroid was prescribed in only 10.92% of the visits. The National Asthma Program was undertaken by The National Health Security Office during 2010 to 2012 to improve asthma management using the Easy Asthma Clinic Model. Method The program supported setting up the Easy Asthma Clinic in the hospitals throughout Thailand. The Easy Asthma clinic is the simplified specialized asthma clinic running by GP. In the clinic we simplified asthma guidelines and organized the system to facilitate the team work, emphasized the role of nurses and pharmacists to help doctors. We also developed on-line web database for registering and monitoring patients. The National Health Security Office also reimbursed for the use of inhaled corticosteroids. Introduction Allergic bronchopulmonary mycosis (ABPM) is characterized by type I, III, and IV allergic reactions to fungal antigens. Sero-positive ABPM (s-ABPM) has specific IgE and IgG antibodies to fungal antigens; this condition precedes ABPM characterized by centri-lobular bronchiectasis. We investigated differences in the production of Th17 cells (CD4 + T cells producing IL-17) and regulatory T (Treg) cells (FOXP3 + CD4 + T cells) between patients with ABPM, s-ABPM, and bronchial asthma. Methods We recruited 20 patients with ABPM, 11 patients with s-ABPM, and 74 patients with bronchial asthma. The diagnosis of ABPM was based on the Rosenberg criteria, and s-ABPM was defined as the presence of specific IgE antibody and an antigen-specific precipitating antibody to fungal antigens by Ouchterlony double immunodiffusion testing in the absence of centri-lobular bronchiectasis. We used flow cytometry to examine the percentages of FOXP3 + CD4 + T cells and CD4 + T cells producing IL-17 in the peripheral blood in our patients with ABPM, s-ABPM, and asthma in the phase without exacerbations.

The percentage of CD4 + T cells producing IL-17 was greater in patients with ABPM (P < 0.01) or s-ABPM (P < 0.05) than in those with asthma. Patients with ABPM had fewer (P < 0.01) FOXP3 + CD4 + T cells than did the other 2 groups. However the percentage of FOXP3 + CD4 + T cells did not decrease in patients with s-ABPM compared with those with bronchial asthma. Conclusion Among patients with ABPM or s-ABPM, peripheral Th17 cells increased relative to the production of specific IgE or IgG antibodies to fungal antigens in serum. The maintenance of FOXP3 + CD4 + Treg cells in patients with s-ABPM may suppress a progression to ABPM. 3 Minami Tokushima Clinic, Tokushima, Japan, 4 Naga Hospital, Wakayama, Japan Background The relationship between allergic rhinitis and asthma is well accepted, however little is known about the mechanism underlying the interactions between the upper and lower airways. Objective To investigate the symptomatic and inflammatory linkages between allergic rhinitis and asthma in atopic patients. Methods We enrolled 520 asthmatics taking inhaled steroids, and examined them using the Asthma Control Questionnaire (ACQ), spirometry, exhaled nitric oxide fraction (FENO), visual analog scale (VAS) for nasal symptoms, allergic rhinitis questionnaire, and serum specific IgE (study 1). The symptomatic and inflammatory marker responses to nasal steroids in patients with incompletely controlled asthma (ACQ > 0.75) and moderate/severe persistent allergic rhinitis were also investigated (Study 2). Results A total of 348 patients (66.9%) had atopy and allergic rhinitis. There was a striking difference in the proportion of patients with incomplete asthma control depending on the presence as well as the activity of rhinitis (no rhinitis, 11.0%; mild intermittent, 20.4%; moderate/severe intermittent, 44.6%; mild persistent, 53.1%; moderate/severe persistent, 65.7%). The FENO levels were increased with the activity of rhinitis, and the nasal VAS was positively correlated with the FENO levels (r = 0.31, p < 0.0001). The additive treatment with nasal steroids improved the nasal VAS, ACQ, and FENO levels, and the changes in these variables were correlated with each other in all parameters (all p < 0.001). Conclusions This observational study of atopic patients indicates that the ongoing allergic rhinitis is related to worsening of asthma by enhancing the lower airway inflammation. Evaluation of the activity of allergic rhinitis appeared to be useful for assessing the impact of rhinitis on asthma, and effective intervention in that area could improve the management efficacy.

YOTARO TAKAKU 1,2 , KAZUYUKI NAKAGOME 1, 3 Background Eosinophils play an important role in the pathogenesis of bronchial asthma and its exacerbation. Recent reports suggest the involvement of IFN-γ-inducible protein of 10 kDa (IP-10) in virus-induced asthma exacerbation. The objective of this study was to examine whether IP-10 modify the effector functions of eosinophils. Methods Eosinophils isolated from the blood of healthy donors were stimulated with IP-10 and the generation of eosinophil superoxide anion (O2-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated to determine whether IP-10 induced eosinophil degranulation. Cytokine and chemokine production by eosinophils was examined using a Bio-plex assay. Results IP-10 significantly induced eosinophil O2-generation in the presence of ICAM-1. The enhanced O2-generation were inhibited by an anti-β2 integrin mAb or an anti-CXCR3 mAb. IP-10 increased the release of EDN. IP-10 increased the production of a number of cytokines and chemokines by eosinophils. Conclusions These findings suggest that IP-10 can directly upregulate the effector functions of eosinophils. These effects might be involved in the activation and infiltration of eosinophils in the airway of asthma, especially in virus-induced asthma exacerbation.

Background The reduction of mortality rate of bronchial asthma is inversely related to the wide spread of inhaled corticosteroid use. In addition, devices of combined inhaled corticosteroids and long-acting beta-agonists have contributed the ease of controlling asthma symptoms in patients with asthma. Currently, there are two different available devices of combined inhaled corticosteroid and long-acting beta-agonist, salmeterol/fluticasone (SFC) and formoterol/budesonide (FBC) in Japan, but these drug profiles are different and the effect of switching from FBC to SFC is still unclear. Patients and Methods Asthmatic patients treated with FBC for more than two months with persisting asthmatic symptoms (scores of Asthma Control Test; ACT less than 25 or scores of Asthma Control Questionnaire 5; ACQ5 more than 0). The times of 0, 4, 12 and 24 weeks after switching from FBC to SFC, asthmatic symptoms assessed by ACT and ACQ5, and spirometric analysis (FVC, FEV1, FEV1%, PEF, V50, V25) were evaluated. Airway resistance was assessed by Impulse Oscillation System, and exhaled levels of nitric oxide were measured by NioxMino in available patients. Monthly costs of asthma treatment in these patients were also evaluated. Results Asthmatic symptoms assessed by ACT an ACQ5 were not statistically significant after switching from FBC to SFC. Spirometric analysis also revealed that the change of FVC, FEV1, FEV1%, PEF, V50, V25 were not statistically significant after switching from FBC to SFC. In addition, monthly costs for bronchial asthma treatment in these patients were significantly reduced after switching from FBC to SFC. Conclusion Switching from FBC to SFC seems to be an alternative treatment option in terms of not only effectiveness of treating asthma but also treatment costs in patients with asthma. Background The prevalence of elderly asthmatics is increasing and the mortality and morbidity are higher than young asthmatics. The characteristics of atopy, bronchial hyperresponsiveness and lung function in elderly asthmatics is worthy of further investigation in order to facilitate asthma management. Methods In this retrospective, hospital-based study, 992 asthmatic patients, who were newly diagnosed or untreated (>3 months) at outpatient clinic, were recruited and divided into two groups, young (age < 65 years; mean, 32.4 ± 7.7 year old, n = 476) and elderly (mean, 75.2 ± 7.7 year old, n = 516) asthmatics. Lung function, methacholine provocation test (MCT)/bronchodilator test (BDT), smoking history, atopy (defined as positive serum allergen immunoassay), and serum IgE level were obtained. Results The prevalence of atopy and serum IgE level was significantly lower in elderly group compared with that in young group. The bronchial hyperresponsiveness and reversibility (determined by MCT and BDT) were similar in both groups. In general, patients with bronchial hyperresponsiveness had poor forced expiratory volume in one second predicted value (FEV1 % pred.) and higher proportion of atopy. Elderly asthmatics with atopy had worse FEV1 than elderly non-atopic asthmatics (70.3 % vs. 77.6% pred.). On the contrary, young atopic asthmatics had better FEV1 compared with young non-atopic asthmatics. Young atopic asthmatics were significantly associated with airway hyperresponsiveness than young non-atopic asthmatics (p = 0.002). This was not observed in the elderly group. Conclusions The characteristics of atopy, bronchial hyperresponsiveness and lung function in elderly asthmatics are different from those in young asthmatics. This may reflect the distinct pathophysiology, at least in part, in the elderly asthmatic airway. Background Since fractional concentration of exhaled nitric oxide (FeNO) was set for monitoring of airway eosinophilic inflammation in asthma, the clinical value in real life practice has never been investigated. Materials and Methods Cross sectional study in adult asthma patients treated at Ramathibodi Hospital between 2012 and 2013. FeNO was measured using portable analyzer NOBREATH® (Bedford UK.). The FeNO was expressed as ppb after 10 second-exhalation through 10 cmH2O positive pressure assuring velum closure. Asthma control was simultaneously assessed by Thai version asthma control test questionnaire (ACT) each visit. Data were analyzed by SPSS version 17. Results There were 83 consecutive patients completed acceptable FeNO measurement at outpatient clinic. Mean age was 58.5 ± 14.1 years. Female patients were 71.1 %. Asthma treatments were mainly ICS-LABA combination. Asthma control test score (ACT) was performed prior to physician visiting. Therefore, patients were classified as controlled asthma (ACT > 19) and uncontrolled asthma (ACT <= 19). Among patients who were labeled uncontrolled asthma patients (n = 32), mean FENO was 57.0 ± 30.1 ppb. In addition, mean FeNO of controlled asthmatics (n = 51) was 61.8 ± 38.5 ppb. The measured FeNO as not significantly different between two groups of patients (p value 0.52). Conclusion Despite the presence of controlled asthma assessing by composite score of asthma control (ACT), substantial numbers of patients have considerably high FeNO representing persistent eosinophillic airway inflammation. Discussion: High FeNO level may warrant physicians that those patients who have persistent airway eosinophilia are susceptible to loss of asthma control after discontinuing or reducing asthma treatment. Introduction Asthma in the elderly is associated with poor outcome. Physical and cognitive function impairment may be contributing factors. Material and Methods Cross sectional study in patients aged over 60 years in 2009. Clinical data regarding asthma were collected and physical function and cognitive function was tested. Results Total 110 elderly with asthma were sampling from asthma clinic having mean age 69.9 years. Female were 78.2 % and overweight were 34.5% of patients. Airflow obstruction was graded as mild, moderate and severe in 38.2%, 22.5% and 14.7%. Common medical co-morbid were hypertension, dyslipidemia, rhinitis and arthritis. Most commonly prescribed inhaled therapy was corticosteroid and long acting β agonist (58.2%) while most common oral agent was theophylline (47.3%). Regarding inhaler devices, MDI was prescribed in 47.3% followed by turbuhaler (24.5%), accuhaler (20.2%) and MDI with spacer (8.2%). Un-scheduled visit due to asthma worsening in past year was noted in 31.8%. Patients ACT score classified as 25 (15.5%), 24-20 (72.7%) and less than 20 (11.8%). Low handgrip strength measured by using dynamometer (<18 kg) was noted in 43.6%. Resting and intention tremor were noted in 2.7% and 13.6%. Complete incisor was noted in 77.3%. All patients have normal mini-mental status examination or MMSE (6-10 points). Inhaler device technique was assessed and graded as good technique in 44.5%. There was no association between hand grip strength and ability to press canister (p < 0.086). Nevertheless, incomplete incisors are associated with ability to completely cover mouthpiece for MDI use. Conclusion Significant proportion of uncontrolled asthma and experienced unplanned visits were observed in elderly. Half of cases have poor inhaler techniques which may be related to physical impairment. Discussion: Despite of the appropriate asthma pharmacotherapy, majority of elderly are uncontrolled. Inhaler device technique problem related to physical impairment has to be concerned in these patients. Objective To improve the understanding of supraglottic neurofibroma, and discuss the atypical clinical signs of larynx neoplasm. Methods A case of supraglottic neurofibroma diagnosed in April 2013 was reported and the related literatures were reviewed. Results A case of a 26 year-old female patient, who had been misdiagnosed as bronchial asthma in local hospital, was admitted to our hospital because of short of breath after exercise for half a year and aggravated for 14 days. After admission, the bronchoscopy showed a giant space-occupying lesion which was located above the glottises and has smooth surface with completely encapsulated in supraglottic interarytenoid region. Subsequently, tumor resection under laryngoscope and general anesthesia was proformed. Pathology report after operation showed spindle cell tumor. Immunohistochemistry showed CD34(++), Bcl-2(+) and S-100(++). Accordingly, it was diagnosed as supraglottic neurofibroma. The symptom of short of breath was disappeared after operation. So far, there was no local recurrence and distant metastasis with 2 months follow-up. Conclusions Supraglottic neurofibroma is rarely occur in the larynx and is easy to be misdiagnosed. To make a definite diagnosis relys on histopathology and immunohistochemistry test especially for the positive result of S100. If met such patients clinically, only if we carefully ask case history and do physical examination, combine of clinical symptom, pay attention to the distinction of wheezing sound between upper and lower respiratory tract, can we effectively lower misdiagnosis possibility, give timely diagnose and right treatment. Objectives We analyzed the relationship between SNP of TSLP (rs3806933) and atopic status, PF and AHR in asthmatics. Methods We recruited 280 asthmatics to the current study who visited the asthma out-patient clinic in Iwate Medical University Hospital from 2006 to 2012. Subjects were genotyped using rs2289276 and rs3806933 by 7500 Fast Real-Time PCR System, (Applied Biosystems USA). PF was evaluated by spirometer. AHR to methacholine was measured by Astograph; Jupitor 21 (Chest, Japan). AHR was expressed as D min (U). This study was approved by the ethics committee of Iwate Medical University. Results Genotyping of rs3806933 showed that 165 C/C, 115 C/T and 19 T/T. Atopic status between C/C and C/T+T/T was significantly different (Chi-square analysis). Neither PF or D min of the 3 genotypes was not significantly different. However there was a significant difference of FEV1 %predicted between C/C and C/T+T/T in never smoker with asthma (p = 0.015, Mann-Whitney U-test). Conclusion SNP (rs3806933) in TSLP was associated with atopic status and FEV1 %predicted in the never smoker of the current asthmatic population, suggesting that TSLP was involved in immune response induced by allergens and modification of immune reaction by smoking. Background In the daily care of asthma, the degree of airflow obstruction as measured through spirometry is used as an index of asthma control, but because the implementation of spirometry requires the maximal forced expiration of the subject, this examination is a burden for elderly subjects. Impulse oscillation system (IOS) is able to measure airway resistance and reactance under quiet breathing using impulse waves. However, the usefulness of evaluating IOS parameters in elderly asthmatics is not clear. We investigated the usefulness of IOS and the correlation between IOS and spirometry in elderly patients with asthma. Method IOS, spirometry and flow volume curve were performed for 51 elderly (65 years old or older: elderly group) and 58 non-elderly (below 65 years old: non-elderly group) patients with asthma. Results There were significant correlation between IOS parameters (R5, R5-R20, Fres, X5) and lung function (%FEV1, %Vdot50, %Vdot25, %MMF) in each group. R5, R5-R20, X5 and Fres were significantly correlated with age, with Fres showing the strongest association. R5 (0.30 vs. 0.40, P < 0.01), R5-R20 (0.04 vs. 0.10, P < 0.01) and Fres (11.92 vs.15.83, P < 0.05) were significantly higher in the elderly group compared with the non-elderly group. X5 showed significantly low value in the elderly group than in the non-elderly group (−0.11 vs. −0.15, P < 0.05). Conclusion These results suggest that IOS can be used to reveal small airway lesions in elderly patients with asthma and is useful as a method of evaluating airway lesions in patients with asthma. Background WHO acclaimed that between the year of 2002 until 2020 the estimation of one billion population will be infected by tuberculosis. Indonesian Health Ministry had performed sensitivity survey in Papua on 2003, with MDR TB as much as 2 % among new case TB and 14.7% among previously treated cases. The resistance of more than two 1st line anti-TB drugs leads to poor sputum conversion and treatment failure. This study aims to find the correlation between 1st line anti-TB drugs sensitivity test and sputum conversion after intensive phase on new case TB patients. Methods This is a prospective analytic cohort study performed in the DOTS outpatient clinic at Dr. Soetomo Teaching Hospital during September 2011 until December 2011. Nineteen patients were enrolled in this study. All participants were new case, sputum positive who met the inclusion and exclusion criteria. Result Of 19 sputum positive new case TB patients, 14 patients (73.7%) were sensitive to first line TB drugs, 3 patients (15.9%) were mono-resistance, 1 patient (5.3%) was poly-resistance, and 1 patient (5.3%) was MDR. Among 14 fully susceptible patients, 13 (92.2%) showed sputum conversion; 2 of 3 mono-resistance patients showed sputum conversion; patient with poliresistance showed sputum conversion. There was no conversion reported on MDR-TB patient at the end of intensive phase. Conclusion There was no significant correlation between sensitivity test result and sputum conversion at the end of intensive phase in the new case, sputum positive TB patients treated with first category TB drugs. Key Word(s) TB new case, sensitivity test, sputum conversion.

A 26-year-old woman presented initially to Phnom Penh Heart Center with chief complaints of chest pain and dyspnea. As a heart investigation was normal and Chest X ray shows an atelectasis of a lower lobe of the left lung she has been referred to the oncology ward of Calmette Hospital for a further investigation. She presented with three-moth history of dry cough, shortness of breath, anorexia, weight loss, and a progressive back pain. She lived with her mother who has been treated for pulmonary tuberculosis 3 years ago. On physical examination she was thinly built and her vital signs were stable. There was no lymphadenopathy, enlargement of liver or spleen. The examination of respiratory system revealed diminished vesicular breath sound and vocal resonance in the left lower lung. Other examinations were unremarkable. She could not obtain available sputum sample for the examination of acid-fast bacilli. Complete blood count was normal (WBC: 7.04 giga/L, RBC: 5.85 tera/L, Hb: 133 g/L, Platelete: 380 giga/L), CRP: 0,29 mg/L, renal function test and liver function test were normal and HIV serology was negarive. The chest radiography showed an atelectasis of a lower lobe of left lung. The chest computed tomography demonstrated a mass of left lower lobe, with destruction of vertebral body of T11. Flexible bronchoscopy showed a mass of carina where the biopsy was performed. The result of anapathology showed an inflammatory reaction of granuloma tissue suggestive of tuberculous infection. The patient was put on a classic antituberculosis treatment (Category I: 2HRZE/4HR). After one month of treatment, she reported a remarkable improvement of her symptoms with an increased appetite. We carried out this study to assess the current prevalence of MDR-TB in new and previously treated cases of pulmonary TB in Varanasi district, Uttar Pradesh, and our observations on transmission of MDR isolates among populations in and around this area. Methods A total of 713 M. tuberculosis isolates were obtained from 1691 patients diagnosed as pulmonary tuberculosis (PTB), of which 298 were from untreated subjects and 415 were from patients who were treated for tuberculosis in the past. Sputum samples were cultured on Lowenstein-Jensen media to isolate Mycobacteria. Drug susceptibility patterns of isolated M. tuberculosis isolates were recorded using 1 per cent proportion method. Transmission of MDR isolates in community was accessed by random amplified polymorphic DNA (RAPD). Isolates showing same band pattern on RAPD were retyped using different primers targeted to the inverted repeat sequence of IS6110 copies in M. tuberculosis genome. Results 1. Prevalence of MDR was 18.6 per cent, initial and acquired being 10.3 and 26.4 per cent respectively. 2. Prevalence of resistance to any drug, MDR and individual drug resistance to isoniazid, streptomycin, ethambutol and rifampicin was significantly higher in patients who were treated in the past. 3. Genotypically similar clusters were seen at all levels of health care. It was not always possible to establish geographic connections within clusters. Conclusion High prevalence of both initial and acquired MDR was noted in M. tuberculosis isolates collected from pulmonary tuberculosis patients. Presence of small clusters of MDR isolates at all health care levels suggests transmission within the studied community. Background Gaining bronchial washing is useful for diagnosis of pulmonary tuberculosis (TB), in patients with negative sputum smear or lack of sputum. However, the benefit of gaining serial bronchial washing specimens for TB diagnosis has not been studied. Therefore, we conducted a retrospective study to determine the diagnostic utility of additional bronchial washing specimens in suspected patients. Methods A retrospective analysis was performed on 174 patients [sputum smear-negative, n = 95 (55%); lack of sputum specimen, n = 79 (45%)] who received bronchoscopy with two bronchial washing specimens with microbiological confirmation of TB in Samsung Medical Center, between January, 2010 and December, 2011. Results TB was diagnosed by first bronchial washing specimen in 141 patients (81%), and an additional bronchial washing specimen established diagnosis exclusively in 22 (13%) patients. Smear for acid-fast bacilli was positive in 46 patients (26%) for the first bronchial washing specimen. Thirteen patients (7%) were positive only on smear of an additional bronchial washing specimen. Combined smear positivity of the first and second bronchial washing specimens was significantly higher compared to first bronchial washing specimen alone [Total cases: 59 (34%) vs. 46 (26%), p < 0.001; cases for smear negative sputum: 25 (26%) vs. 18 (19%), p = 0.016; cases for poor expectoration: 34 (43%) vs. 28 (35%), p = 0.031]. The diagnostic yield determined by culture was also significantly higher in combination of the two serial bronchial washing specimens compared to the first bronchial washing. [Total cases: 163 (94%) vs. 141 (81%), p < 0.001; cases for smear negative sputum: 86 (91%) vs. 73 (77%), p < 0.001; cases for poor expectoration: 77 (98%) vs. 68 (86%), p = 0.004]. Conclusions Obtaining an additional bronchial washing specimen could be a beneficial and considerable option for TB diagnosis in patients with smear negative sputum or lack of sputum specimen.

[Correction added on 23 October 2013, after print publication and first online publication: Conclusion section was edited to include the last text, "in patients with smear negative sputum or lack of sputum specimen" in abstract PS129.] 

Patient is E.R. a 57 yo female, non-smoker seen at the outpatient for 4 weeks history of non-productive cough and hoarseness. There was no note of fever, weightloss and anorexia. She was treated as a case of pnuemonia, given several courses of antibiotics with no relief. 1 week after, there was difficulty of breathing and difficulty in sleeping described as choking sensation. Patient had stable vital signs, afebrile, 98% O2 saturation at room air, stridor and basal ronchi. Laryngoscopy showed hyperemic vocal cords with a polypoid mass on the right vocal fold. Cxray: infiltrates on the left upper lobe. Ct scan showed ground glass opacities in the superior segment of both lower lobes,fibrosis left apical lobe and narrowing of the right main stem bronchus and no lymphadenopathies. Neck Ct scan : no masses, but with irregular borders on the right bronchus,collapse of the right upper lobe Bronchosocpy : cobble stoning with hard protruding cartilaginous structures covered with cottony exudates seen from the trachea to the right main bronchus. Bronchial washing was positive for Kliebsiella Pnuemonia. Biopsy showed cartilage and fibrin material with inflammatory cells. AFB stain was positive for acid fast bacilli. She was started on INH/RIF/PZA/EMB for 6 months. Rigid bronchosopy was done to remove the remaining cartilaginous material. Histopathology confimed the diagnosis of Tracheopathiaosteochondroplastica revealing cartilage with areas of ossification. There was note of improvement of symptoms. Tracheopathiaosteochondroplastica is a rare disorder of affecting the large airways. It is described as multiple osseous and cartilageinous nodules in the submucosa of the trachea and main bronchi. Ecchondrosis, exositosis from tracheal rings or metaplasia of submucosal and connective tissue cartialage and/or bone tissue are theories to its development. The association of this rare disease entity with active pulmonary tuberculosis has not been presented. The new tuberculosis patients are treated by standard medication regimen which has influenced to be hepatitis which may be severe until death. Hepatitis patient must stay in hospital and some of them are died because of severe hepatitis. This study is to examine prevalence and risk factors that influence to hepatitis. Descriptive retrospective study 187 samples treated at Uttaradit hospital in Uttaradit province, Thailand, South-east Asia from 1st January 2011-30th June 2012. The characteristic, medicine, liver function test, risk factors were collected and analyze from patient profile and question the patients. The result shows the hepatitis are male (16.4%), female (18.5%). There is a relationship between level of malnutrition and hepatitis (p = 0.043), then malnutrition stage is severe (20.7%), moderate (16.2%), mild (24.5%) and normal experienced hepatitis (5.4%) respectively. Risk factors (p = 0.017) influence hepatitis consisting of chronic diseases (45.2%). In addition, high dose of medicine induce hepatitis about 25 times of normal dose significantly (p = 0.033). Malnutrition induce hepatitis about 8.18 times of normal nutrition (p = 0.031). In conclusion, high dose of medicine, malnutrition and chronic diseases influence to induce hepatitis. Hence, the pharmacists must evaluate risk factors for monitoring liver function test and counseling the patient to evaluate sign/symptoms with themselves for preventing severe hepatitis. Key Word Risk factor, hepatitis, Thailand. Psoas abscess is a rare clinical disorder which be a primary; following haematogenous dissemination or a secondary one; with local extension of an infectious process near the psoas muscle. Our case was a 21 year old male patient. His complaints presented as cough (began 8 months ago, more evident at last 2 months), loss of appetite, fatigue, weight loss (8 kg approximately), night sweat, back pain. The patient was a textile worker, nonsmoker. On physical examination; fever 36,7C, blood pressure 120/80 mmHg, pulse 84/min, breathing was 22/min, lomber and parasacral regions were painful with palpation. Right hip extension was painful, right hip joint range of motion (ROM) was limited. Posteroanterior chest X-ray revealed no abnormality but in lower sections of thorax CT a retroperitoneal abscess was observed. At lumbar MR dated 2/14/2013: the view was evaluated as psoas abscess with spondylodiscitis. He was BCG vaccined and his PPD was 10 mm. CRP: 85, ESR: 95 mm/h Serological tests: Rose Bengal test was negative. 24 hours urine smear was AFB (-) negative respectively. Sputum smear and culture results were reported as AFB (-) negative three times. He was HIV (-) negative. the case evaluated as a seconder psoas abscess with local extension of spondylodiscitis. The abscess was fully drained with an operation. The abscess material was AFB (+) positive with EZN staining. So a short course tuberculosis treatment was started on 02.20.2013 with (INH, RIF, ETB, MPZ). After two months dual treatment (INH, RIF) was continued. In the process patients pain was decreased, night sweat decreased, had an increase in body weight of 8 kilograms, also as an interesting finding his cough was disappeared. After 3 month treatment regimen a control MR was seen; complete response was achieved. Background Urogenital tuberculosis is a common extrapulmonary manifestation of primary tuberculosis and is caused by the dissemination of Mycobacterium tuberculosis from the primary complex. Although the incidence of urogenital tuberculosis is 15-20% from extrapulmonary tuberculosis, but the diagnosis of urogenital tuberculosis is not easy. Case A 44-years-old female came to Sanglah Hospital with chief complaint dysuria. She also complained of right back pain, hematuria and fever. She had an unclear history of lung tuberculosis. From the urology USG we found right moderate hydronephrosis with simple cyst and cystitis. Retrograde pyelography-ureterorenoscopy showed ureter stricture et causa suspicion of urethritis tuberculosis. The PCR TB from the pus was positive. Conclusion A 44-years-old female with chief complaint dysuria, after undergone a series of examination and tests was diagnosed with urogenital tuberculosis. Patient was given antituberculosis drugs. Keywords tuberculosis, urogenital, pcr. Background and Aim of the Study The TBDC is a committee that is responsible for evaluating cases of TB symptomatics that are smear (-), but whose chest radiographs show lesions suggestive of tuberculosis. It was set up originally by the Department of Health, National TB Program (NTP) with the advise by WHO-Western Pacific Regional Office. The meetings being held at least every two weeks at University of Santo Tomas Hospital (UST), Manila, Philippines (high TB burden country). This study aimed to describe the demographic profile of patients referred to the committee. Methods All outpatient and inpatient cases of the UST Hospital seen by TBDC from March 2012 to March 2013 were included in the study. A review of TBDC forms was done. The summary of report for each meeting was tabulated and descriptive statistics was done using SPSS version 16. Results 211 patients were included in the study. 50.2% are males, most are 60-70 years old, 67.3% are non smokers, and 77.3% have no other known co-morbidities, but for those with co-morbidities, 10% are hypertensive, 3.8% diabetic and 2.8%known cancer. 57.8% have prior intake of anti-TB medications, of at least one month or more, in which 18% have completed outcome while 14.2% are not known. Majority (65.4%) have active TB requiring treatment under Category I and 26.5% under Category II. Most have multiple signs and symptoms, namely cough, weight loss and dyspnea. The common chest x-ray findings include fibrotic and ill defined infiltrates (74%), fibrocystic, fibronodular and granuloma (24%), suspicious fibrotic infiltrates (18%), cavitary (14%) and disseminated TB (14%). Conclusion Clinicians must look into the many possibilities why direct sputum smear microscopy of a number of patients with cavitary and disseminated TB are negative. A significant percentage of patients are also Multi Drug Resistant TB(MDR-TB) suspects.

KENJIRO SHIMA 1 , TAKURO SAKAGAMI 1 , YOSHINARI TANABE 1 , NOBUMASA AOKI 1 , HIROSHI MORO 1 , TOSHIYUKI KOYA 1 , TAKASHI HASEGAWA 2 , EI-ICHI SUZUKI 2 , ICHIEI NARITA 1 1 Division of Respiratory Medicine and Infectious Disease, Niigata University, Niigata, Japan, 2 Department of General Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan Rationale All of exposed subjects with non-tubelculouse mycobacterium (NTM) species do not develop active infection, which likely reflects underlying host susceptibility factors. Recent reports have shown that anti Interferon-Gamma (IFN-gamma) neutralizing autoantibodies (IFN-gamma Ab) are associated with disseminated NTM patients without known evidence of immunodeficiency. The purpose of this study is to establish the screening method if subjects have IFN-gamma Ab. Here, we report a novel bioassay to evaluate IFN-gamma signaling in whole blood and human T-cell line with patients plasma based on IFN-gamma stimulated, IFN-gamma receptormediated phosphorylation of STAT1, which is named the STAT1 phosphorylation index (STAT1-PI). Method Blood was obtained from patients with disseminated NTM, pulmonary NTM and healthy controls. To evaluate neutralizing capacity to IFN-gamma, STAT-1 phosphorylation in leukocyte and T-cell line after stimulation with various concentrations of exogenous IFN-gamma (ranging from 1 to 1000 ng/ml) was evaluated by using flow cytometer. The strength of phosphorylation was described as STAT1-PI which was calculated as the mean fluorescence of cells primed with assigned concentration of IFN-gamma minus that of unprimed cells divided by that of unprimed cells multiplied by 100. Antigen capture assay was performed to measure the relative titer of Ig-G fraction of IFN-gamma Ab. Result The STAT1-PI increased in proportion to IFN-gamma concentration reaching a maximum value near 1000 ng/ml and to time reaching in 30 minutes after stimulation. STAT1-PI with plasma from disseminated NTM patients was inhibited, while it from other disease and healthy subjects were not (n = 6: 7.3 plus or minus 27.8, n = 3: 424.8 plus or minus 21.9, n = 6: 243.4 plus or minus 133.9, p < 0.01). All of subjects with inhibited STAT1-PI have high concentration of IFN-gamma Ab(mean: 493 E.U.). Conclusion The STAT1-PI is simple, useful flow cytometry-based method to measure IFN-gamma signaling in the evaluation of disseminated NTM patients suspected of having IFN-gamma Ab.

Backgrounds The bacteriologic diagnosis in pulmonary tuberculosis is confirmative, even though successful rates in self-expectorated sputum are limited. In the previous studies, sputum specimens induced by hypertonic saline nebulization facilitated bacteriologic diagnosis with higher sensitivity over those from selfexpectorated sputum. The benefits of the sputum induction were investigated in the diagnosis of pulmonary tuberculosis. Methods A prospective randomized case-control study in one hospital. The subjects highly suspicious of pulmonary tuberculosis were asked to provide 3 pairs of sputum specimens in 3 consecutive days. The first pairs of the specimens were obtained either by self-expectoration (SE) from the next day of the visit or sputum induction with 7% saline nebulization at presentation (HS) and the other pairs were collected in the same ways. The samples were used for acid fast bacilli staining, mycobacterial culture and PCR. The outcomes of bacteriologic detections were compared. Results Seventy one patients were assigned either into SE (35 subjects, age of 52 ± 17, 69% male) and HS (36, 54 ± 17, 47%). Forty one subjects with pulmonary tuberculosis (57.7%) and 3 with non-tuberculous mycobacterial infection (4.2%) were diagnosed. At presentation, 21 (60%) of SE and 20 (55.6%) of HS revealed scanty amounts of sputum. (p = 0.705) In the mycobacterial detection, HS (13 subjects, 36.1%) and SE (13, 37.1%) showed no difference. (p = 0.928) Consequently, 22 (62.9%) of SE and 19 (52.8%) of HS were clinically diagnosed and treated as pulmonary tuberculosis. (p = 0.39). Conclusions Sputum induction with hypertonic saline, even in patients with scanty sputum does not facilitate the bacteriologic confirmation of pulmonary tuberculosis.

Background and Aim of Study Both chronic hepatitis C virus (HCV) infection and pulmonary tuberculosis (TB) are prevalent worldwide, however, the association between HCV infection and pulmonary TB is not completely understood. Methods We identified 4,094 adults newly diagnosed with hepatitis C infection in 2002-2004 from the Taiwan National Health Insurance Research Database. Comparison group consisted of 16,376 adults without hepatitis C infection randomly selected from the same dataset, frequency matched by age and sex. Events of pulmonary TB from 2002 to 2008 were ascertained from medical claims (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM, codes 011). Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for potential associated factors including HCV infection, age, sex, low-income status, urbanization, cessation of cigarette smoking, alcohol-related illness, obesity, history of chronic diseases and medication use. Results During the follow-up period, there were 293 newly diagnosed pulmonary TB cases. After adjustment, the results showed that male (HR = 2.26, 95% CI = 1.77-2.88), age with 10-year increment (HR = 1.07, 95% CI = 1.06-1.08), and low-income status (HR = 1.94, 95% CI = 1.11-3.38) were risk factors for the risk of pulmonary TB. The cumulative risk of pulmonary TB for people with hepatitis C and without HCV infections was 2.1% and 1.3%, respectively (p < 0.0001). Compared with people without hepatitis C infection, the adjusted HR of pulmonary TB was 1.62 (95% CI = 1.24-2.11) for people with HCV infection. Conclusion Chronic HCV infection increases the risk of pulmonary TB and should be considered an important and independent risk factor. Background and Aim of Study Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy. This study aims to investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9 + Vδ2 + T cells, CD4 + T cells and CD8 + T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection. Methods Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry. Results Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8 + T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17 kDa, 15 kDa and 9 kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed. Conclusion The results suggested that the alteration of circulating granulysin, perforin and IFN-γ have potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection. Results Pulmonary tuberculosis was confirmed by sputum culture on 79 patients. MDR-TB was confirmed as etiology in 11 (13.9%) patients, 4 patients with new onset and 7 patients in recurrent pulmonary tuberculosis. Among patients with MDR-TB, there were 9 (81.8%) male and 2 (18.2%) female patients. Median age was 35 years. Four (36.4%) patients were diagnosed as HIV patients at admission, 5 (45.5%) patients had HIV for less than one year, and 2 (18.2) patients had HIV for more than one year. The most presenting symptoms were cough (81.8%), fever in 72.7%, night sweat 72.7%, and weight loss (100%) with mean BMI 18.8 kg/m 2 . The median mean LED was 94.9 mm/ hour and CD4 at diagnosis was 40 cells/ml. Normal plain chest radiography was seen in 4 patients. The most common abnormality found in plain chest radiography was bilateral extensive lungs infiltrate (5 patients). Conclusion MDR-TB in Indonesia presented with high frequency. Early detections of MDR-TB should be performed in HIV patients with pulmonary tuberculosis since the clinical features were similar with pulmonary tuberculosis due to non MDR-TB pathogen. Key Word clinical profile, HIV, MDR-TB.

Introduction Massive hemoptysis is frightening event for many patients and one of respiratory emergency that is associated with high mortality. Tuberculosis, along with bronchiectasis and lung abcess, account for 90% of cases. Case report We report 46 years old male patient, refererred with chief complain of hemoptysis 9 days before admission. Patient had a history of tuberculosis 3 years prior and several rehospitalisation because of hemoptysis. Chest radiograph showed old tuberculosis lesion at right upper lobe. Sputum and bronchoalveolar lavage smear examination result was negative for acid fast bacilli. Chest CT scan showed lung cavity which pulls trachea to lateral. Flexible bronchoscopy showed teleangiectasia at one third distal portion of trachea. Broncoalveolar lavage was taken, and citology result was suppurative inflammation. Despite medication, patient still experienced recurrent hemoptysis. Patient was planned to undergo thoracothomy procedure to control bleeding. Conclusion Pulmonary fibrosis caused by cicatrix in airway and lung parenchym is one of tuberculosis sequelae. Other complication is hemoptysis caused by rupture of Rasmussen aneurysm. Surgery option may be taken to treat recurrent and uncontrolled bleeding. Key Words hemoptysis, tuberculosis sequelae, lung fibrosis. Background and Aim of the Study Tuberculosis is one of the most common presenting illness and the leading cause of death among HIV-infected patients. HIV infection increases the risk of pulmonary tuberculosis due to MDR-TB. It's still unknown whether the occurence of recurrent increase the event of MDR-TB infection in patients with HIV. We investigated associations between pulmonary tuberculosis category and MDR-TB infection event in patients with HIV. Methods We performed a cross-sectional study to HIV-infected patients with pulmonary tuberculosis during January 2012 to April 2013 in Cipto Mangunkusumo Hospital. MDR-TB was confirmed by phenotypic drugsusceptibility testing. We compared the proportion of MDR-TB event between new onset (Group-1) and recurrent (Group-2) pulmonary tuberculosis with Fisher's exact test. Results A total of 79 patients were involved in this study, 47 patients were included in Group-1 and 32 patients were included in Group-2. MDR-TB was found in 11 patients, 4 patients in Group-1 and 7 patients in Group-2. Fisher's exact test showed no difference of MDR-TB infection event between groups (p = 0.109). Conclusion Recurrence of pulmonary tuberculosis was not related to the increasing event of MDR-TB infection in patients with HIV. Key Words HIV, recurrent, MDR-TB.

Background and Aim of the Study Tuberculosis (TB) is the most common opportunistic infection and the main cause of death in patients infected with Human Immunodeficiency Virus (HIV). TB-HIV cases showed a marked increase during the last few years. There has not been any study on the profile of TB-HIV patients in Cipto Mangunkusumo Hospital. The aim of this study is to assess the demographic, clinical, laboratory and radiologic characteristics of TB-HIV patients. Methods We conducted a descriptive cross-sectional study by browsing through the medical records of TB-HIV patients who seeked medical treatment to Integrated HIV Outpatient Clinic (POKDISUS), Cipto Mangunkusumo Hospital within the period of July 2008-July 2012. Patients' medical records and confidentiality was maintained throughout the study. Results A total of 667 patients were eligible as study subjects, mostly males (79.6%) and majority were in the 18-40 age group (91%). Demographic characteristics showed the following: 55.1% were married, 29.2% belonged to Batavian ethnic group, and 64.2% of the subjects were high school graduate. Transmission through intravenous drug user was the main mode of transmision (62.9 %). Oral candidiasis (37.12%) and hepatitis C (24.6%) were the most common co-infections. Chronic cough was the most common clinical manifestation (62.9%), followed by prolonged fever (53.8%) and weight loss (49.9%). Negative Acid Fast Bacilli smears were found in 39.6%, 51.3% had CD4+ counts of lt; 200 cells/μ 181;L and 47.4% showed radiologic (chest X-ray imaging) characteristics of TB. Conclusion Profile of TB-HIV patients in our study is more or less similar with studies reported from other developing countries. High rate of intravenous drug user as mode of transmission showed the need for intervention in order to reduce this risk factor. Background Intracellular cytokine flow cytometry (ICCFC) has been explored to detect tuberculosis (TB) infections; however, there are little data regarding its use to examine the dynamic responses of Mycobacterium tuberculosis (MTB)-specific T-cells after anti-tuberculous therapy. The aim of the present study was to analyze both dynamic changes in functional MTB antigen-specific T-cell subsets and interferon-gamma (IFN-γ) levels using ICCFC and the QuantiFERON-TB Gold In-Tube (QFT-IT) test, respectively, following anti-tuberculous treatment in patients with active TB. Methods Twenty-six patients with active TB were enrolled in the study, and QFT-IT and ICCFC were performed simultaneously both before and after treatment. IFN-γ levels (QFT-IT test) and the numbers of IFN-γ-or tumor necrosis factor-alpha (TNF-α)-expressing T-cells (ICCFC assay) were examined after stimulation with MTB antigen. Results There was no significant reduction in the mean IFN-γ concentrations measured by the QFT-IT test after anti-tuberculous treatment (p = 0.314). ICCFC analysis showed that the numbers of IFN-γ + /CD4 -T-cells and CD4 + Tcells producing TNF-α, either alone or in combination with IFN-γ, were significantly reduced after anti-tuberculous treatment. The IFN-γ + /TNF-α + /CD4 + T-cell subset showed the greatest difference between untreated and treated patients with active TB (area under the curve = 0.734, p = 0.004). Conclusions Unlike the QFT-IT test, ICCFC provides diverse immunological information about dynamic changes in the number of MTB antigen-specific T-cells following anti-tuberculous therapy. Thus, analysis of MTB antigenstimulated T-cell responses using ICCFC might have a role to play in monitoring treatment responses in patients with active TB. Conclusion The treatment outcome for ofloxacin-resistant MDR-TB patients was significantly better for those with moxifloxacin-susceptible TB than for those with moxifloxacin-resistant TB. Background Early diagnosis and treatment of nontuberculous mycobacterial lung diseases (NTM-LD) and pulmonary tuberculosis (PTB) are important clinical issues. The present study aimed to compare and identify the chest CT characteristics that help to distinguish NTM lung disease from PTB in patients with acid-fast bacilli (AFB) smear-positive sputum. Methods and Patients From January 2009 to April 2012, we received 467 AFB smear-positive sputum specimens. A total of 95 CT scans obtained from the 159 patients were analyzed, 75 scans were from patients with PTB and 20 scans from NTM-LD. The typical chest CT findings of mycobacterial diseases were analyzed. Results In patients with PTB, the prevalence of pleural effusion (38.7% vs. 15.0% ; P = 0.047), nodules < 10 mm in size (76.0% vs. 25.0%; P < 0.001), tree-in-bud pattern (81.3% vs. 55.0%; P = 0.021), and cavities (31.1% vs. 5.0%; P = 0.018) were significantly higher than patients with NTM. Of the 20 patients with NTM lung diseases, honeycomb appearances were significantly higher than patients with PTB (20.0% vs. 4.0%; P = 0.034). In multivariate analysis, CT scan findings of nodules was independently associated with patients with diagnoses of PTB (odds ratio = 0.07; 95% confidence interval [CI], 0.02-0.30). Presence of honeycombing in CT scans was strongly associated with patients with NTM-LD (OR, 33.04; 95% CI, 3.01-362.55). Conclusions The CT distinction between NTM-LD and PTB may help radiologists and physicians to know the most likely diagnoses in AFB-smear positive patients and avoid unnecessary adverse effects and the related costs of anti-TB drugs in endemic areas.

YI-WEN HUANG 1,2 , HSIN-CHIEH TSAI 1,2 , THOMAS CHANG-YAO TSAO 1 1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, 2 Pulmonary and Critical Care Unit, Changhua Hospital, Department of Health, Changhua, Taiwan Background Sputum examinations are still the gold standard to confirm tuberculosis and to evaluate treatment outcome of anti-tuberculosis medication. However, poor quality of the sputum can lead to a lack of growth from the specimen. This study aims to investigate the sputum detection rate by comparing two collection methods (1) the negative pressure room (spot) and (2) at home (early morning). Methods Subjects in Changhua hospital presented with cough over 2 weeks, sputum, abnormal X-Ray or with existing tuberculosis were included in the study. All sputa were taken after subjects rinsing with distilled water. The spot collection was performed in the negative pressure room with supervision from a medical staff. Home (early morning) collection was undertaken when the patient first woke up. All the sputa were smeared and cultured, and the results were compared and analyzed to determine the positive tuberculosis (TB) rate, nontuberculous mycobacterium (NTM) rate and contaminate rate. Results A total of 1294 set sputum samples were collected from 01 January 2010 to 31st December 2012 and analyzed in this report. The early morning sputa generally yield the best number of organisms, however, our study showed a higher positive TB detective rate from the spot collection (5.6%) than the early morning collection (4.9%). The NTM (15.2%) and contaminant rates (3%) were much higher in the early morning collection than in the spot collection (7.6% and 0.9% respectively). These could be due to poor sputum quality collected from home as subjects failed to rinse with distilled water before sputum collection, and a lack of staff supervision and collection of saliva instead of the deep respiratory secretion from the chest. Conclusion The supervision of the medical staff and rinsing with distill water were found to improve the quality of the sputa.

Background Tuberculosis can occur anywhere in the body, but most of the lung parenchym. Factors that play a role in the control of M.tb infection are T cells, macrophages, and cytokines IFN-γand TNF-α. After fagosits M.tb, macrophages stimulated to produce TNF-α. TNF-αcauses proinflammatory cells migrated transendothelial to the lungs to form a granuloma which prevents the spread of M.tb by locking it. The aims of this study to identify and analyze the mean levels of TNF-αin pulmonary TB patients and those without TB, and investigate the relationship of TNF-αlevels with the incidence of pulmonary TB that can be used in the evaluation of TB treatment. Method A case-control prevalence analytical design with cross sectional approach. Performed in the pulmonary clinic and inpatient of internal medicine of RSMH Palembang, from March 2012 to January 2013. Samples that meet the inclusion and exclusion criteria drawn up by consecutive sampling until number of 30 cases and 60 controls. Results A total of 90 subjects, comprising of 57% men and 43% women with a mean age of 37 years. TNF-αcut-off point levels is 2.927 pg/ml, odds ratio 2.983 and 95% confidence interval 1.202-7.408. The mean TNF-α serum level in pulmonary TB is 6.99 ± 10.45 pg/ml, were significant higher than no TB 3.59 ± 3.11 pg/ml. Conclusion There is significant difference TNF-αserum level in pulmonary TB and no TB. There is a significant association between TNF-α serum level with pulmonary tuberculosis incidence. Keywords Pulmonary tuberculosis, TNF-α.

Background T cell helper-1 (Th-1) plays an important role in immune system, especially for intracellular bacterial infections. One of the cytokines produced by Th-1 cells is interferon-gamma (IFN-γ), which plays an important role in eliminating the M.tuberculosis. This study aimed to see if there was a level of IFN-γwith pulmonary TB incidence. Method Serum levels of IFN-γwere measured by ELISA in 30 TB patients, 32 patients with tuberculin test >10 mm and 28 patients with tuberculin test < 10 mm. We use Receiver Operating Characteristic (ROC) and Odd Ratio (OR) to analyze the relationship between the levels of IFN-γwith tuberculosis. Result The result of the IFN-γserum levels of 30 pulmonary tuberculosis patients obtained 11.80 ± 9.55 pg/mL with a range from 4.54 to 43.90 pg/mL, 32 subjects with tuberculin test >10 mm 8.36 ± 1.76 pg/mL with a range of 5.56 to 12, 80 pg/mL, and in 28 subjects with tuberculin test < 10 mm 7.99 ± 1.81 pg/mL with a range from 5.82 to 12.90 pg/mL. There were no significant differences in serum IFN-γlevels between the three groups (p = 0.210). Cut-off point gained 8.43 pg/mL with a sensitivity of 60% and specificity of 62%. There was no significant association of serum levels of IFN-γwith the incidence of pulmonary tuberculosis (p = 0.052). Conclusion There were no significant differences among the three groups and no correlation with the incidence of pulmonary tuberculosis. Serum levels of IFN-γcan be used as a marker of TB infection but can not determine active or latent TB. Key Words Pulmonary tuberculosis, tuberculin skin test, IFN-γ.

SUZANNA JAPPAR, SU YING LOW Singapore General Hospital, Singapore

Background Poor compliance to tuberculosis (TB) treatment has many adverse consequences including longer treatment period, drug resistance, relapse and the possibility of infecting others. Aim To profile tuberculosis patients who missed their appointments. Method Between June and December 2012, all patients who were actively followed up for TB but missed their scheduled appointments were contacted via telephone to elucidate reason for default. Results Over the 6 months, there were a total of 319 patients accounting for 879 visits to Singapore General Hospital (SGH) for follow up of TB treatment. 78 (24.5%) patients were absent for their appointments whereby 53(67.9%) patients missed once, 18(23%) patients missed twice only and 7(9%) patients missed more than twice. Patients treated were mostly Singaporean (85%), male (64.3%), Chinese (67.1%), and age greater than 65 years old (32.9%). However, Malays (40.4%) were likely to miss their appointments. Further analysis, showed 55.6% of patients between 10-19 years old missed their appointments, more than twice that of patients in other age range. Unfortunately, a large proportion couldn't be contacted via telephone to elucidate reason for default. However, common reasons for defaulting were readmission to hospital (25.6%), patients forgetting appointments (11.5%), migration (11.5%) and death (3.8%). Patients older than 65 years old were likely absent due to readmission to hospitals (44%) and foreigners, tended to be absent due to migration. Of patients who missed appointments the first time, letters were sent to 29 patients and 14(48.3%) returned for follow-up. Of patients who missed appointments the second time, recall letters were sent to 10 patients and 4(40%) returned. Conclusion From our profile, Malay ethnicity and patients between 10-19 years have a higher risk of default. Success rate with recall letter was around 50%. Implementation of pre-TB treatment education could improve patients' understanding of the disease and importance of compliance to treatment and perhaps reduce defaulter rates. Background and Aim of Study The primary source of exercise limitation in people with chronic obstructive pulmonary disease (COPD) is dyspnoea. Part of the cause for this has been attributed to changes in chest wall mechanics, with a decrease in chest wall mobility contributing to the decrease lung function. As manual therapy (MT) is known to increase joint mobility, administering MT to people with COPD introduces the potential of reversing this process, even if only for the short term. The aim of this trial was to investigate the effect on lung function of including MT in a pulmonary rehabilitation (PR) program for patients with COPD. Methods 33 participants with COPD, aged between 55 and 70 years (mean = 65.5 years ± 4), were randomly assigned to three groups: PR only, soft tissue manual therapy (ST) and PR, and ST and spinal mobilisation (SM) and PR. Outcome measures were recorded at 0, 8, 16 and 24 weeks. Results A clinically significant increase was reported in forced vital capacity (FVC) between the three groups at 24 weeks (p = 0.03). For the ST+SM+PR Group versus PR only the increase was 0.44 litres (SE: 0.16; p = 0.02). In the six minute walking test (6MWT), despite a significant difference between groups at 16 weeks (p = 0.01), individual group increases were not significant. No major or moderate adverse events were reported following the administration of 131 ST and 272 SM interventions. Conclusion The increase in FVC is a unique finding. Although the underlying mechanisms responsible for this outcome are not yet understood, the most likely explanation is a synergistic effect resulting from the combination of interventions. These results support the call for further investigation into the use of MT for COPD.

Background As per the chronic obstructive pulmonary disease (COPD) Management Network of the Ishinomaki District, our hospital manages pulmonary rehabilitation (PR) of COPD patients of this area. Methods Sixteen consecutive male COPD patients (mean age, 73 ± 6 years old) were enrolled. The COPD patients were diagnosed by a pulmonologist at a general hospital, and were referred to our hospital for PR. We assessed symptoms, respiratory muscle strength and flexibility, breathing pattern and 6-minutes walk distance, and prepared individually suitable rehabilitation programs. Every 1-2 weeks, the patients underwent PR which involved light-, moderate, and heavy-intensity exercises. Their symptoms, respiratory muscle strength and flexibility, breathing method learning, exercise tolerance, activities of daily living (ADL), mental state, spirometry, and blood gas analyses were monitored. Results Seventy-five percent of the patients were GOLD Stages II and III, and equal number were grades 1 and 2 on MRC Breathlessness Scale. Thirty percent scored above 5 on the BODE Index. Before PR, the mean FEV1 was 52.5 ± 24.3% predicted (GOLD Stage II), FEV1/FVC was 40.8 ± 12.3%, and 6-minute walk distance was 311 ± 109 m. The above parameters were unchanged after 27 ± 13 months of PR. ADLs were preserved (Group P) or ameliorated (Group A) in 75% of the patients, and deteriorated (Group D) in 25%. Before PR, Group A had a significantly lower 6-minute walk peak heart rate (HR) (90.5 ± 6.6) than Group P (105 ± 10, p = 0.028). Group D had significantly lower rate of good training comprehension (33.3%) than Group P (85.7%, p = 0.044). PR improved ADL. Six-minute walk peak HR and good training comprehension were associated with good PR outcome. Conclusion PR was useful for preservation and improvement in ADL of COPD patients. The physiological value of Tai Chi (TC) as a useful mode of pulmonary rehabilitation in COPD remains poorly understood, especially in comparison with the generally accepted threshold of 60% of maximal load which is considered necessary for pulmonary rehabilitation. we compared the physiological work, judged by oxygen uptake, esophageal pressure swing and diaphragm electromyography, entailed by TC compared with that entailed by constant rate treadmill walking at 60% of maximal load. Quadriceps fatigue after both these tasks was assessed. Eleven patients (age 62 ± 8 years) with a range of COPD severity (FEV1 61 ± 27 % of predicted) were studied. The intensity of workload entailed by TC did not differ from treadmill walking at 60% VO2max but only TC elicited quadriceps fatigue (mean fall in Tw Q 12.6%, P < 0.01). Conclusions TC constitutes a physiologically sufficient stimulus to exercise load to be useful for pulmonary rehabilitation which may be culturally more acceptable in some parts of the world.

Background and Aim of Study COPD assessment test (CAT) is a useful tool to evaluate health-related quality of life (HRQOL) of COPD outpatient. Although the ECLIPSE study showed that HRQOL is a predictive factor of acute exacerbation in addition to a history of prior exacerbations, it is little known whether CAT score predicts acute exacerbation of COPD. We aimed to investigate the influence of CAT scores on incidence of acute exacerbation of COPD. Methods We enrolled 287 COPD outpatients in our hospital and observed them for 1 year. We measured body mass index (BMI), CAT scores, pulmonary function tests and a history of at least one acute exacerbation in the previous year, then we analyzed correlation between incidences of acute exacerbation for the next year. Acute exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization. Results Exacerbations occurred in 27% of all patients in 1 year. In univariate analysis, BMI, CAT scores, a history of exacerbation within the previous year, VC (%pred), FEV1 (%pred) and FEV1/FVC indicated significant correlations between incidence of acute exacerbation for the next year. In multivariate analysis, only CAT scores (HR = 1.06, p = 0.006) and a history of exacerbation within the previous year (HR = 4.76, p < 0.0001) were good predictive factors of acute exacerbation. Conclusion In addition to prior exacerbations, CAT scores can predict acute exacerbation of COPD.

HARUHIKO HIRATA 1 , HIROKO KITAOKA 2 , TAKASHI KIJIMA 1 , OSAMU HONDA 3 1 Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan, 2 Division of Engineering Technology, JSOL Corporation, Nagoya, Japan, 3 Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan Rationale Functional disorder of the pulmonary emphysema has been believed due to dynamic compression of peripheral small airways caused by decrease of parenchymal elastic recoils. However, direct evidences of the proposed mechanism have never been shown. We have analyzed end-inspiratory and end-expiratory 3D-CT data sets, and proposed a hypothesis that overinflated lungs compressed the inra-mediastinal airway (IMA, intra-thoracic trachea, main bronchi, and right lobar bronchi) at the beginning of forced expiration and would let IMA collapse due to Bernoulli's effect in emphysema patients (presented inAPSR2006). However, breathhold static images could not reflect dynamic behaviors during breathing. Objectives We evaluated the morphological and volumetric changes of IMA during maximum forced expiration by 4D-CT, and investigated its relationship to the value of FEV1.0. Method Five emphysema patients and a normal subject underwent 4D-CT by multi-detector row CT during maximum forced expiration over 6 sec at supine posture. Voxel size was 0.7 × 0.7 × 1.0 mm 3 and time interval was 0.35 sec. Volumes of intra-thoracic trachea and bilateral main bronchi are measured through expiration, and the relative volume to the volume just before the beginning of forced expiration was calculated for each frame. Results The IMAof all emphysema patients were extremely narrowed immediately after the beginning of forced expiration and slightly recovered later. The membranous part of IMA was invaginated inside. There was no apparent shape change in the normal subject. The 2 sec-relative volume were highly correlated to FEV1.0 (r 2 = 0.93). Conclusion These 4D-CT images have revealed that low values of FEV1.0 in emphysema patients are caused by dynamic collapse of IMA due to Bernoulli's effect. Current concepts of respiratory mechanics, pulmonary function tests, and COPD should be urgently reconsidered. Background Roflumilast an oral, selective phosphodiesterase-4 inhibitor has been shown to improve lung function in COPD patients. We investigated whether Roflumilast along with conventional therapy would improve lung function in Bangladeshi COPD patients. Methods A single blind, randomized, placebo controlled study was carried out in the department of Respiratory medicine at National Institute of Diseases of the Chest and Hospital (NIDCH), Dhaka, Bangladesh. 130 patients were recruited initially and randomly distributed into Group-A where patients got conventional therapy (Inhaled Salmeterol + Fluticasone and Tiotropium) and Roflumilast (0.5 mg once daily) and Group-B where patients got placebo with conventional therapy. Study duration was 3 months. Patients developing exacerbations and requiring emergency treatment were excluded from the study. 46 patients in group-A and 50 patients in group-B completed the study. A spirometry and CAT (COPD assessment test) score was performed in each case at the beginning and monthly for 3 months. Difference of mean FEV1 and CAT-score from baseline between two groups was measured to assess the Roflumilast activity. The primary outcome variable was change in mean FEV1 and secondary outcome variable was change in mean CAT score from base line.

Results Clinical characteristics of the study population in terms of cough, dyspnoea, wheeze, sputum production, loss of weight and appetite were not statistically significant. In group A, mean FEV1 increased and mean CAT score changed at all three visits. The change was statistically significant. Conclusion COPD patients who received Roflumilast along with conventional therapy experience better lung function and symptomatic improvement than conventional therapy alone. Results Of the 563 patients randomised, 561 (89.8% Chinese) received study treatment and 482 completed the study. At Week 12, trough FEV1 improved significantly for both indacaterol doses vs placebo (p < 0.001), with indacaterol-placebo differences exceeding the pre-specified minimal clinically important difference of 0.12 L (0.15 and 0.13 L for indacaterol 150 and 300 μg, respectively). TDI score at Week 26 was superior to placebo for both indacaterol doses (0.82, 1.15 points; p < 0.01), as was the percentage of patients with clinically relevant improvement (≥1 point; 74.1%, 78.6% vs 55.5%; p < 0.05). At Week 26, both doses provided ≥4-point improvements from baseline in SGRQ score that were numerically greater than placebo (unadjusted means: -9.6, -8.8 vs -7.0 points). A similar pattern was seen in the percentage of patients with clinically relevant improvements in SGRQ score (65.0%, 61.5% vs 60.6%). Incidences of adverse events were comparable across the treatment groups. Conclusion Indacaterol provided effective bronchodilation in predominantly Chinese population, with significant improvements in breathlessness and health status. Background and Aim of Study Arterial blood gas analysis shows various indicator in patients with acute exacerbation of COPD (AECOPD) has been evaluated. Aim of this study is to investigate the characteristic of arterial blood gas analysis and its relationship with mortality. Methods In a retrospective cohort study, we analyzed medical records of 36 male adults hospitalized with AECOPD in Persahabatan Hospital from March 2011 to February 2013. Arterial blood gas parameters such as pH, pCO2, pO2, HCO3 and SaO2 were analyzed on admission and during hospital stay. Results A total of 36 hospitalized AECOPD patients (mean age 66.61 ± SD 9.13; BMI 19.20 ± SD 3.24) were included. There was no significant association between age, Brinkman Index, BMI and BUN with mortality rate. The acid-base balance rate on admission were normal 44.44% (n = 16), acidosis 27.78% (n = 10), and alkalosis 27.78% (n = 10), hyperoxia 52.8% (n = 19), hypoxia 33.3% (n = 12), hypercapnia 44.4% (n = 16), hypocapnia 16.7% (n = 6). The acid-base balance on follow up was normal 50% (n = 18), acidosis 33.33% (n = 12), alkalosis 16.67% (n = 6), hyperoxia 25% (n = 9), hypoxia 52.8% (n = 19), hypercapnia 44.4% (n = 16), hypocapnia 16.7% (n = 6). The mortality rate was 22.22% (n = 8). There was significant mean difference in pO2 level on admission (109.40 ± SD 51.69 vs 95.71 ± SD 30.21, p < 0.05), pCO2 level on follow up (68.81 ± SD 39.14 vs 45.98 ± SD 8.38 p < 0.05) and SaO2 level on follow up (82.36 ± SD 15.56 vs 93.98 ± SD 8.38, p < 0.05) between death and survive patients. There was no correlation between pO2 level on admission and pCO2 level on follow up. Conclusion Arterial blood gas parameters have significant relationship with mortality in hospitalized AECOPD patients. The alteration of pO2, pCO2 and SaO2 might help clinicians in patient management to decrease hospital mortality rate. Background As a global health problem, COPD may contribute to significant health problems during pilgrimage for moslems. Indonesian Ministry of Health documented acute exacerbation of COPD (AECOPD) as the second leading causes of death in pilgrims with 12.3% of total mortality in 2008. Identifying individuals with higher risk to have AECOPD prior to their embarkation is essential. Therefore, the use of CAT scores in assessing risk of acute AECOPD in this special population merits further investigation. Methods This is a cohort study recruiting 61 COPD patients at Jakarta embarkation point where patients completed CAT. Subjects and their pilgrims groups' doctors were given diary cards to record any symptoms of exacerbation during pilgrimage. On arrival at disembarkation point, subjects underwent history taking, health examination and all diary cards were collected. AECOPD were determined from the diary cards and individual health record book carried by every pilgrim. Results All patients completed the study. Most subjects were male (57; 93.4%) with a mean age for this study is 58.8 ± 8.5 years. Thirty five patients (57.4%) suffered from AECOPD during pilgrimage. CAT scores range from 0-25 with a mean of 8.2 ± 5.5. Subjects within low impact group (CAT score < 10) comprised 63.9% of subjects while the remaining 36.1% were in medium to high impact group (CAT score 10-30). Mean CAT score in exacerbation group were significantly higher than in non-exacerbation group (10.2 ± 5.2 vs. 5.4 ± 4.8, p = 0.00, independent t-test). Conclusions This study indicates that the use of CAT may be a valuable tool in identifying individuals at risk of AECOPD prior to pilgrims' embarkation. Background Chronic obstructive pulmonary disease is multisystemic inflammation with high morbidity and mortality. Comorbid anemia was common in patients with chronic disease and eosinopenia as marker of inflammation has been evaluated. This study investigate the prevalence association of anemia, eosinopenia with mortality rate and rehospitalization in patients with COPD excacerbation. Methods A retrospective study analyzed medical record 59 male adult hospitalized for COPD excacerbation in Persahabatan hospital from January 2011 to December 2011. Hemoglobin (Hb) and eosinophil on admission were assesed. Patients were classified as anemic (Hb < 13 g/dl) or non-anemic and eosinopenic (eosinophil count < 50 cell/mm 3 ) or non-eosinopenic. We calculate the prevalence of anemia, eosinopenia and compared with mortality rate and rate of rehospitalization in 1 year. Results A total of 59 patients hospitalized for COPD excacerbation (mean age 66.51 ± SD 8.63; Hb 13.65 ± 1.84; FEV1% predicted 46.9 ± 18.41) were included. Prevalence of anemia was 28.8% (n = 17) and eosinopenia 32.2% (n = 19). There was no significant association between age, brinkman index, BMI, FEV1% predicted, cardiovascular and diabetes mellitus comorbid with anemia and eosinopenia. One year mortality rate was 28.8% (n = 17) and rate hospitalization ≥ 2x per year in survived patient was 28.6% (n = 12). Independent predictors of one year mortality were eosinopenia (p < 0.05) and FEV1% predicted (p < 0.05). One year mortality rate was significantly different (p < 0.05) between eosinopenia group (52.6% vs 17.5%; RR 3.01; 95%CI 1.36-6.67) and non-eosinopenia. Anemic patients had higher risk rehospitalization ≥ 2x/year than non-anemic patients (54.5% vs 19.4%; p < 0.05 0.05; RR 2.82; 95%CI 1.15-6.92). Conclusion Eosinopenia might be a useful predictor to predict mortality and anemia to predict rehospitalization in patients with COPD excacerbation. As it was routinely given in blood count in all patients admitted to hospital, there was no extra cost for this beneficial test. Background and Aim of the Study Chronic Obstructive Pulmonary Disease (COPD) is a major cause of mortality and morbidity around the world. Majority of COPD patients experience at least one exacerbation per year, and the frequency of exacerbations increases with disease severity. Increased number of exacerbations is reported to have a more rapid decline in FEV1. The aim of this research is to evaluate the incidence of exacerbations and the changes in lung function in our patients who are on regular follow up. Method We conducted a cross-sectional study on a cohort of COPD patients who are on regular follow up at Asthma/COPD outpatient clinic in our hospital from 2011 until 2013. Patients were interviewed and spirometry was performed, which was then compared with spirometry data of 2011. Retrospective analysis of their medical records was done for exacerbation events in the last two years which lead them to seek medical care. Results Total of 32 patients (M = 31, F = 01) were evaluated. Fifteen percent (n = 5) were below 60 years of age and 27 (84.4%) above 60 years of age. Disease severity as per GOLD were; mild disease 21.9%, Moderate 71.9% and severe 6.25%. A total of 129 exacerbations were recorded (average 2.02 exacerbations/patient/ year). Patients with infrequent exacerbations 56.25% (n = 18) had an average 124.5 ml decrease in FEV1 value and patients with frequent exacerbations 43.75% (n = 14) had a decline of FEV1 average 187.25 ml/year. Conclusion Patients with a higher number of exacerbations had greater decline in FEV1. Key Words COPD; exacerbation; lung function; FEV1.

Background In patients with chronic obstructive pulmonary disease (COPD), multidetector-row computed tomography (MDCT) showed that tiotropium dilated the inner diameters in airways from the third to the sixth generation of the bronchi. Here we aimed to evaluate the morphological effect by adding a budesonide/formoterol combination to tiotropium in COPD patients using three-dimensional MDCT. Methods Pulmonary function tests, St. George's Respiratory Questionnaire (SGRQ) and MDCT imaging studies were performed at the beginning and after budesonide/formoterol combination treatment for 12 weeks in 14 patients with COPD. Results The median age was 73.5 years and the mean forced expiratory volume in 1 second (FEV1) as a percentage of the predicted value was 57.2 ± 18.3 %. The average luminal area and wall area percentage in the third, fourth and fifth generations were correlated with the SGRQ total score. Budesonide/formoterol induced insignificant pulmonary function changes and significant symptoms improvement. CT images showed an increased inner luminal area and decreased wall area after budesonide/ formoterol treatment. Average luminal area was significantly increased from 24.3 ± 9.7 to 26.0 ± 9.9 mm 2 in the third generation, 13.0 ± 6.5 to 14.7 ± 7.3 mm 2 in the fourth generation, 8.0 ± 4.8 to 9.4 ± 4.9 mm 2 in the fifth generation and 5.6 ± 2.7 to 6.7 ± 3.6 mm 2 in the sixth generation (p < 0.01). The wall area percentage significantly decreased from 51.5 ± 9.2 to 49.1 ± 9.7 % in the third generation, 56.1 ± 9.7 to 53.0 ± 11.1 % in the fourth generation, and 62.3 ± 9.9 to 57.6 ± 9.8 % in the fifth generation (p < 0.05). Emphysema volume/CT-derived total lung volume was unchanged with treatment. Conclusion MDCT demonstrated budesonide/formoterol-induced bronchodilation in the non-small airway. CT imaging can evaluate drug therapeutic effect and may provide additional insights into pharmacotherapy for COPD. Nutritional Status greatly affects the patient. Subjective Global Assessment is well validated screening tool for malnutrition. It is the aim of this study to determine the correlation of Nutritional Status using SGA on Pulmonary Function Parameters of newly diagnosed and already diagnosed COPD patients according to GOLD criteria seen at the Philippine Heart Center. This is a Cross Sectional Study. Patients 40 years old and above diagnosed with COPD are included. Nutritional status were assessed using anthropometric indices such as weight, height, Body Mass Index (BMI), Mid Arm Circumference (MAC) and Subjective Global Assessment. The association of anthropometric parameter with pulmonary function was determined using Pearson correlation analysis. Analysis of variance was used to determine relationship of malnutrition and pulmonary function. A p-value of < 0.050 was considered significant. One hundred fourty-five COPD patients participated in the study. Forced Vital Capacity (FVC) decreases as the patient became malnourished. The difference proved to be significant (p = 0.000). Forced Expiratory Volume in 1 second (FEV1) showed the same significant decrease as the patient became malnourished (p = 0.000). The FEV1/FVC ratio diminished from a well nourished patient to a severely malnourished patient which proved to be likewise significant (p = 0.000). Among the anthropometric measurements performed, weight and mid arm circumference have positive correlation with FEV1 (p = 0.016; p = 0.000) and FEV1/FVC ratio (p = 0.001; p = 0.001). BMI was noted to be positively correlated with FEV1/FVC ratio (p = 0.001). However, no correlation was noted on both leukocyte count and albumin with PFT parameters. Nutritional Status assessed using Subjective Global Assessment correlates significantly with FEV1, FVC, FEV1/FVC ratio of COPD patients. Body weight, MAC and BMI were found to have positive correlation with PFT results of COPD patients. SGA, weight, MAC, BMI can be a gauge to monitor the severity of COPD without doing frequent PFT especially among difficult, critically ill COPD patients. Background Tiotropium is a recently developed inhaled anticholinergic, used at once-daily dosing in the management of COPD. Previous studies have hinted that long-term use may lead to an increased risk for cardiovascular mortality. In 2010, the US-FDA issued a statement indicating the cardiovascular safety of Tiotropium based on the UPLIFT trial (2008), the largest and longest placebo-controlled trial on Tiotropium. However, there is still question on Tiotropium's cardiovascular safety, especially in comparison to active treatment, particularly, inhaled long-acting beta-agonists. Objectives We determined the efficacy of long-term tiotropium use on clinical endpoints such as mortality, exacerbations, and hospitalizations compared to inhaled LABAs among patients with stable moderate to severe COPD. Methodology RCTs were identified from electronic databases such as PubMed, Cochrane Library, Ovid, Herdin, Clinicaltrials.gov and Google Scholar. Relevant studies and reviews were also hand-searched. RCTs among patients with COPD comparing Tiotropium monotherapy with inhaled LABAs with at least 6 months follow-up were selected. Data on all-cause mortality, mortality from pulmonary and from cardiovascular causes, rates of hospitalizations and exacerbations were identified. The date of last search is September 7, 2012. Two independent investigators evaluated and extracted relevant data, which were analyzed using Cochrane Review Manager 5.1. Results From 495 titles and abstracts, 5 clinical trials with a total of 10,759 patients met inclusion criteria. Tiotropium did not reduce all-cause mortality (RR 0.83 95%CI 0.40-1.70), mortality from respiratory causes (RR 0.70 95%CI 0.40-1.25), and mortality from cardiovascular causes (RR 1.57 95%CI 0.86-2.85). Tiotropium significantly decreased the risk for exacerbations (RR 0.91 95%CI 0.85-0.98), and exhibited a trend towards decreased hospitalizations (RR 0.78 95%CI 0.61-1.00). Conclusions Tiotropium did not reduce all-cause mortality, mortality from pulmonary causes, and mortality from cardiovascular causes compared to inhaled LABAs. Tiotropium significantly decreased the risk for exacerbations, and showed trend towards possible decreased hospitalizations.

Introduction Comorbidies such as diabetes mellitus, hypertension and cardiac disease are commonly reported in patients with chronic obstructive pulmonary disease (COPD). This study aimed to determine the frequency of comorbid conditions and the multimorbidities in hospitalized patients with acute COPD exacerbation. Methods We included COPD patients whom admitted to a tertiary reference center in Southern Marmara Region and hospitalized with acute exacerbation in 2012. Medical records of the study participants were screened retrospectively and comorbid diseases were analyed. Results A total of 75 patients hospitalized for acute COPD exacerbation were included. Of these 88% were males, and 12% were females with a mean age of 68.8 ± 10.2. The prevalence of diabetes mellitus, hyperlipidemia, hypertension and coronary artery diseaese were 14.7%; 6.7%, 26.7, and 22.7% respectively. The multimorbidities were more frequent in females than the male patients with COPD exacerbation (55.6% vs 6.1%, OR: 19.06, p < 0.05). In routine laboratory blood tests on admission serum creatinin levels were higher in COPD patients with multimorbidities than the ones with no comorbid condition (1.1 (min: 0.7-max: 1.8) vs. (0.8 (min: 0.5-max: 8.0), p < 0.05). On the other hand, the red cell distribution width were lower in COPD patients with multimorbidities when compared with the ones having no comorbid condition (15.0 ± 2.1 vs 17.5 ± 4.5, p < 0.05). Conclusion Comorbidities are common in patients hospitalized for COPD exacerbation. Female sex is a significat risk factor for having multimorbidies in COPD patients requiring hospitalization for acute exacerbation. Background/Aims Studies in western countries have shown COPD is associated with significant diurnal symptom variability, notably in the morning. However, it is unknown whether this occurs in Chinese COPD patients with moderate or greater airflow limitation. Methods In a non-interventional, cross-sectional study conducted at 10 hospitals in China involving 323 COPD patients (mean age 65.4) with mostly moderate (n = 152), severe (n = 127) or very severe (n = 42) airflow limitation (GOLD 2011 classification), patients' perceptions of the daily variability of COPD symptoms and the impact of symptoms on their morning activities, sleep quality and quality-of-life (QoL) were assessed via investigator-applied questionnaires. MMRC and CAT questionnaires were also applied for assessment. Results Variability in COPD symptoms during a day was noted in 48.9% of patients overall, and 55.1%/54.8% respectively of severe/very severe airflow limitation patients. The most frequent times when patients were most distressed by COPD symptoms were the morning on waking (33.5% of patients), later in the morning (20.9%), and in the evening (22.2%); in patients with very severe airflow limitation, 56.5% were most distressed on waking. Clinical symptom questionnaires indicated that the major activities adversely affected by COPD symptoms were negotiating stairs (83.6% of patients), physical activity/exercise (89.5%), and shopping (50.8%). Sleep quality was rated by 34.4% of patients as poor. Scores on both the MMRC and CAT questionnaires were significantly correlated with the impact on patients' morning activities (p < 0.0001). Conclusion COPD symptoms in Chinese patients with moderate or greater airflow limitation exhibited diurnal variability, and impacted on their daily living and morning activities and sleep quality. Morning symptoms and morning activity impact due to COPD should be paid more attention by clinical physicians. This study was funded by AstraZenca China and medical writing was supported by Content Ed Net.

Introduction QVA149 is a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237) for the treatment of chronic obstructive pulmonary disease (COPD). The BEACON study evaluated the efficacy and safety of QVA149 compared with the concurrent administration of it monocomponents indacaterol and glycopyrronium (IND+GLY). Methods This multicenter, double-blind, parallel group, active controlled study randomized (1:1) patients with moderate-to-severe COPD to once-daily QVA149 (110 μg indacaterol/50 μg glycopyrronium) and placebo or concurrent administration of indacaterol (150 μg) and glycopyrronium (50 μg) via the Breezhaler ® device for 4 weeks. The primary objective was to demonstrate the non-inferiority of QVA149 versus IND+GLY for trough forced expiratory volume in one second (FEV1) after 4 weeks (non-inferiority margin = −100 mL). Secondary objectives included FEV1 area under the curve from 0 to 4 hours (AUC0-4h) at Day 1 and Week 4, symptom scores, rescue medication use, safety and tolerability. Results Of the 193 randomized patients, 187 (96.9%) completed the study. QVA149 demonstrated non-inferiority versus IND+GLY for trough FEV1 at Week 4 (treatment difference = −0.005 L (95% Confidence interval (CI): −0.051, 0.040). The treatment differences for FEV1AUC 0-4h between QVA149 and IND+GLY at Day 1 and Week 4 were 0.02 L (95%CI: −0.005, 0.054) and −0.01 L (95% CI: −0.059, 0.034), respectively. Both treatment groups had a similar reduction in symptom scores and recuse medication use from baseline. The incidence of adverse events was similar between QVA149 (25.6%) and the IND+GLY (25.2%) groups. No deaths were reported in the study. Conclusion Once-daily QVA149 improved lung function, reduced symptom scores and rescue medication use and had a similar safety and tolerability profile compared with the free combination of its mono-components.

Introduction Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common condition that leads to unscheduled health care utilization and impaired health status among patients. Methods This study assessed the infective etiologies related to AECOPD with molecular techniques including viruses such as bocavirus, human metapneumovirus and novel bacteria like Streptococcous pseudopneumoniae. We also studied paired sputum samples for the same panel of viruses for subjects with positive nasophargneal aspirate (NPA). The relationship between the identification of micro-organisms and short term clinical outcomes of the patients such as hospital length of stay, need for non-invasive ventilation and mortality at 3 months were assessed. Results 323 episodes of AECOPD and 30 control COPD subjects at stable state were studied. Overall, about 20% of the subjects had positive NPA. The commonest viruses identified from the NPA of AECOPD patients were rhinovirus, coronavirus and respiratory syncytial virus. For the control subjects, the commonest organisms detected in NPA specimens were atypical organisms like Mycoplasma pneumoniae (6.5%) and Chlamydia pneumoniae (9.7%). 63.4% of AECOPD patients and 20.8% of control subjects had positive sputum bacterial test. Streptococcus pseudopneumoniae was identified in 29.4% of subjects with AECOPD. Among subjects with positive NPA results, 43.3% showed positive results in paired expectorated sputum. Comparisons of the subjects with same organisms identified in both NPA and sputum versus those in NPA only found similar demographic characteristics and short term clinical outcomes. Conclusion The role of the high prevalence of Streptococcous pseudopneumoniae in sputum of AECOPD patients and atypical organisms like mycoplasma and chlamydia in NPA of stable COPD subjects needs further investigation.

Background Hypoxemia, as a consequent of alveolar hypoxia, increases along with the severity of COPD. Tissue hypoxia triggers the degradation of purine. Serum uric acid (UA), the final product of purine degradation, has been shown to be increased in the hypoxic state. Therefore, serum UA may reflect the severity of hypoxia. We assessed whether the presence of higher values of serum UA is associated with the degree of severity of COPD. Methods The research was conducted in the outpatient pulmonary clinic of Soetomo Hospital, Surabaya, East Java, Indonesia. We included 38 consecutive patients with COPD. Patients were in clinically stable condition and without other significant comorbid conditions. The degree of severity was then compared with oxygen saturation and values of serum UA. Results A weak correlation was found between hypoxemia and the degree of severity of COPD (r = −0.375, p = 0.020). There was no patient with level of saturation less than 80%. Correlation between serum UA value and the degree of severity of COPD presented no significant (r = −0.177, p = 0.288). Conclusion Severity of COPD that is characterized by decrease of lung function (FEV1) did not result in increased levels of serum uric acid in patients with COPD.

Background Systemic inflammation may contribute to cachexia in COPD patients. TNF-α is one of the important biomarker in systemic inflammation. Aim this study was to analyze correlation between systemic inflammation and nutritional status of chronic obstructive pulmonary disease patients. Methods This case-control study was conducted in May up to June 2013. The respondents were stable COPD GOLD I-IV patients, aged 40-80 year. Case was defined as COPD patient with poor nutritional status, control was defined as COPD patient with good nutritional status. Nutritional status was measured using body mass index (BMI), percentage ideal body weight, lean body mass and fat-free mass. TNF-α serum was measured using enzyme immunoassay. The correlation between nutritional status and level of TNF-α serum were analyzed with Univariat and multivariat analysis. Result Mean of TNF-α serum level in case group was higher than control group (49,68 ± 19,23 pg/ml vs 22,22 ± 7,65 pg/ml, p = 0,000). Level of TNF-α serum had correlation with BMI (r = 0,594; p = 0,000), percentage ideal body weight (r = 0,595; p = 0,000), lean body mass (r = 0,594; p = 0,000) and fatfree mass (r = 0,594; p = 0,000). The odds ratio was 28 (CI 95%, 4,43-176,78; p = 0,000). Conclusion TNF-α serum was correlated with decrease of nutritional status in COPD patients. Keywords TNF-α, Tumor necrotic factor, systemic inflammation, nutritional status, COPD. Background and Aim of Study Few surveys have focused directly on physicians' perspectives on treating COPD. The C2C Physician Survey aimed to describe physician beliefs and behaviors related to COPD diagnosis and treatment, including knowledge of Revised GOLD 2011 Strategy, in 12 countries including Japan and Korea. Methods Sampled physicians were identified from in-country professional association databases, including a total of n = 103 in Korea (74% general practitioners [GP], 26% chest physicians [CP]) and n = 101 interviews in Japan (70% GP, 30% CP). Standardized, translated questionnaires were conducted by telephone, face-to-face, or online from January to May 2013. Results Awareness of the GOLD 2011 Strategy was 73% overall in Korea and 54% overall in Japan; knowledge was higher among CPs compared to GPs (Korea 96% vs. 36%; Japan 80% vs. 42%). Spirometry (Korea 86%; Japan 85%) and chest x-ray (Korea 91%; Japan 97%) were commonly used to establish a COPD diagnosis, while use of patient-reported outcomes (Korea 58%; Japan 47%) was lower in both countries. Sixty-five percent of Korean physicians and 47% of Japanese physicians reported that they discuss smoking cessation with their patients at every visit. Perceived patient adherence to prescribed treatment regimen was low, with only 13% of Korean physicians and 17% of Japanese physicians indicating that at least threequarters of their patients always complied with their treatment regimen. Both Korean (47%) and Japanese (57%) physicians indicated medication cost as the most common barrier to accessing and adhering to an optimal regimen. Conclusion Awareness and application of the GOLD 2011 Strategy were high among respiratory specialist physicians in Korea and Japan, and an opportunity to improve general practitioner delivered care of COPD patients was identified. Sponsored by GSK. Objectives We aimed to understand the symptoms, actual daily behavior, and degree of satisfaction of the patients receiving treatment for chronic obstructive pulmonary disease (COPD). Method A questionnaire survey targeting 500 patients in 27 medical institutions specializing in pulmonary medicine was carried out between April and June 2013. We included patients aged ≥ 40 years patients who were visiting a medical institution after being diagnosed with COPD via pulmonary function testing. Further, all patients provided consent for participation in the survey. The treating doctors provided data on the pulmonary function, number of exacerbations, and treatment regimens of their patients. Results Most patients were treated using long-acting inhalational drugs, and the patients indicated a relatively high degree of satisfaction with the treatment. Cough, sputum, and exertional dyspnea, depending on the disease severity, were frequently observed. Most patients reported that cough was the most troublesome, and was accompanied by sputum, during about 2 h after awakening. Exertional dyspnea was also reported to be the most severe on awakening, which continued for about 2 h, and in the afternoon. Patients reported a greater number of exacerbations than did their doctors, which indicated that the doctors probably did not completely understand the suffering of their patients.

MARIE GRACE L. LUANCING 1 , TERESITA S. DE GUIA 2 , ROMMEL T. BAYOT 2 1 Philippine Heart Center, East Avenue Quezon City, Philippine, 2 Philippine Heart Center, East Avenue, Quezon City, Philippines

Background The COPD assessment test (CAT) was developed to assist patients and their clinicians assess and quantify the symptoms and impacts of COPD and enable better communication between patients and physicians about these consequences of their disease. It was already validated to other countries as well in the Philippines and also has strong correlation to SGRQ. Methods The study was a cross-sectional, 254 stable COPD patient were included in the study. CAT and SGRQ questionnaires administered as random basis. Data was described as mean ± sd or frequency (no.) and percent distribution. Kappa test was used to determine significance of agreement of cut-off points of scoring system with severity of COPD as diagnosed by spirometry.

The results obtained showed significant impairment in health status that was related to COPD severity. The COPD severity increases the CAT and SGRQ scores also increases significantly (CAT (p = 0), SGRQ (p = 0.001)). However, there was no significant agreement of cut off scores in CAT with COPD severity. (Kappa test: 0.17 p = 0.009). Conclusion CAT showed significant association in health related impact to COPD severity with good correlation to SGRQ scoring system. Background and Aim of Study 31-day readmission rate is deemed to be an important indicator of the quality of medical care in China. The objectives of this study were to identify the readmission rate of acute exacerbation for chronic obstructive pulmonary disease (COPD) and to evaluate its associated risk factors. Methods We retrospectively reviewed patients with acute exacerbation of COPD (AECOPD) to hospital between January 2011 and November 2012. The early readmission group and non-early readmission group were determined by whether patients were readmitted within 31 days after discharge. Logistic regression analysis was performed to identify risk factors for early readmission following an AECOPD. Results There were 692 patients with 925 admissions during the 23-month period, 63 (6.8%) admissions were defined as early readmission. Multivariate analysis showed that chronic pulmonary heart disease (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.26-3.64, p = 0.005), hypoproteinemia (OR 2.02, 95% CI 1.03-3.95, p = 0.040) and the level of PaCO2 (OR 1.03, 95% CI 1.00-1.06, p = 0.027) were the risk factors for early readmission of AECOPD. Conclusion Readmission rate for AECOPD was high. AECOPD patients with chronic pulmonary heart disease, hypoproteinemia, and high level of PaCO2 are at risk for readmission with 31 days of hospital discharge, and medical care of these patients warrants much greater attention. Background Chronic obstructive pulmonary disease (COPD) has been recognized as a systemic inflammatory disease. Although visceral adipose tissue inflammation is known to be associated with various lifestyle diseases, such as diabetes mellitus and atherosclerosis, its contribution to the systemic inflammation of COPD remains unclear. The aim of this study was to evaluate the association between lung function and visceral adipose tissue inflammation. Methods This study included 82 patients who underwent surgical resection due to an early stage of abdominal cancer, such as gastric and colon cancer. Visceral adipose tissue was obtained during the operation with informed consent. We quantified inflammatory cells in the adipose tissues, and evaluated its association with clinical parameters including lung function. This study was approved by an institutional ethics committee. Results The number of visceral adipose tissue macrophage (ATM) did not show a significant correlation with FEV1% (FEV1/FVC), and was not different between patients with (n = 20) and without airflow limitation (n = 62). However, there was a significant negative correlation between ATM and % predicted VC (r = −0.30, p = 0.006). In addition, there was a significant positive correlation between ATM and body mass index (BMI). The levels of CRP was significantly higher in patients with low % predicted VC. Multivariate analyses demonstrated that % predicted VC and BMI were independently associated with the number of visceral ATM. Conclusion The adipose tissue inflammation may contribute to the systemic inflammation of advanced COPD with low lung volume, independently from BMI.

Background Chronic obstructive pulmonary disease (COPD) is known to be associated with various comorbidities and unfavorable conditions during postoperative period. However, there are limited data on the association between subclinical airflow limitation (AL) and comorbidities. The aim of this study was to evaluate the frequency of preoperative pulmonary dysfunction among various diseases, and to assess the associations of pulmonary dysfunction with clinical parameters including comorbidities and the period of hospital stay. Methods This study included 839 patients who had undergone surgical operation due to breast (n = 256), lung (n = 233), colorectal (n = 122), gastric (n = 256), or cardiovascular disease (n = 77). We retrospectively reviewed their clinical records such as age, sex, body mass index, smoking, underlying diseases, hospital days, and comorbidities such as hypertension, hyperlipidemia, hyperuricemia, and diabetes. We evaluated associations between these clinical parameters and pulmonary dysfunction. Results The preoperative AL was observed in 240 (28.6%) among the patients, whereas only 32 (3.8%) had subjective symptoms and had been diagnosed as having COPD. The % predicted VC was significantly lower in patients with cardiovascular disorder than others. There were different frequencies of AL among patients with cardiovascular (45.5%), breast (7.0%), lung (40.3%), colorectal (32.0%), and gastric disorder (35.8%). Age and male gender were independently associated with the presence of AL. Among comorbidities, only hypertension (58.0% in patients with AL, 39.0% without AL) was significantly associated with AL, independently from age and sex. In addition, significantly longer hospital days were observed in patients with AL (23 days) than patients without AL (17 days) (p < 0.0001). Conclusion Preoperative AL is frequently observed, and is mostly present as a subclinical dysfunction. Preoperative AL is significantly associated with hypertension, and the prolonged hospital days.

ASUKA NAGAI 1 , RURIKA HAMANAKA 2 , AKINORI EBIHARA 1 , TOKUZEN IWAMOTO 1 , ICHIRO KUWAHIRA 1 1 Department of Pulmonary Medicine, Tokai University Tokyo Hospital, 2 

Background and Aim of Study Cardiovascular events such as acute myocardial infarction and stroke are the major comorbidities and the leading cause of death in patients with COPD. Atherosclerotic changes are largely responsible for these events. In the present study, we evaluated the cardiovascular risks in COPD patients by detecting platelet hyperaggregability and measuring high-sensitivity C-reactive protein (hs-CRP) which is a marker of systemic inflammation and carotid max intima-media thickness (Max-IMT). Methods The study included 26 stable COPD patients (stage2-4) and 26 healthy controls. We measured carotid artery Max-IMT using ultrasound imaging, and hs-CRP in venous blood sampling. Regarding hyperaggregability, we analyzed frequency of occurrence of natural platelet aggregates in venous blood using an Abbot CELL-DYN SAPPHIRE hematology analyzer. Results Platelet aggregates were positive in 4 of 26 (15.4%) in COPD patients, but only 1 of 26 (3.8%) in healthy controls. The average value of hs-CRP was 0.136(±0.139, SD) mg/dL in COPD patients and 0.047(±0.063) mg/dL in controls. The average value of the Max-IMT was 1.10(±0.40)mm in COPD patients and 0.96(±0.32)mm in controls. There was a tendency to thickening in the COPD group. Plaque was detected in 91% of the COPD group, but in 54% of the healthy controls.

The results of the present study indicate that patients with stage 2-4 COPD have a significant risk of thrombosis due to atherosclerotic changes, and suggest that early detection of platelet hyperaggregability by the present method are useful for prevention of cardiovascular events. Background Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for patients with stable COPD. Methods Data sources were Medline (from 1948 through October 2011), EMBASE (from 1980 through 20 November 2012), Cochrane Central Register of Controlled Trials, Koreamed and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. Two reviewers independently extracted the data. The outcomes were the exercise capacity as 6 minute walking and adverse events of treatment. Results Four randomized controlled trials involving 109 subjects were included in the analysis. Among the four trials two involved bosentan, one involved sildenafil and one involved beraprost. The studies varied in duration of treatment from 3 months to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio −5.09, 95% CI −13.00 to 2.82). COPD patients with overt PH significantly improved the exercise capacity (mean difference 111.63, 95% CI 63.31 to 159.94) but COPD patients with PH unknown did not (mean difference 26.61, 95% CI −24.31 to 77.52). There was no significant difference in hypoxemia between PH-specific treatment and placebo groups (mean difference 2.55, 95% CI −3.68 to 8.77). Conclusion PH specific treatments have a significant effect in improving exercise capacity in COPD patients with overt PH.

Background Chronic obstructive pulmonary disease (COPD) is one of the common causes of death. However, limited number of patients is properly treated in Japan. One of the reasons is that some of the patients are not recognized and diagnosed by general practitioners (GPs). Throughout the period, the number of doctors who prescribed inhaled long-acting muscarinic antagonist (LAMAs), which is recommended as a first-line treatment by the guideline of the Japanese Respiratory Society, was significantly increased (p < 0.001). However, there was no significant change in the rate of having a spirometer in possession and recognition of the guidelines. When we focused on the survey results from the doctors specialized in internal medicine, the recognition of the guidelines was significantly increased (p < 0.01) despite no change in the rate of having a spirometer in possession. Furthermore, multivariable analysis of the 3rd survey result revealed that doctors who specialized in internal medicine, examined many patients with COPD, and recognized the guidelines prescribed more LAMAs significantly. On the other hand, doctors who did not specialize in internal medicine and examined few patients with COPD did not even know the guidelines. Conclusions Not only educational campaigns but also comprehensive regional medical liaison between hospitals and clinics would be needed. Educational campaigns would be more beneficial when GPs' background was taken into consideration. Background Early initiation of inhalational corticosteroid therapy is useful in certain COPD patients, but associations of COPD signs with atopic factors are not clearly defined. Methods Sixty-eight COPD patients who received medical care in our hospital from 2010 through 2013 were classified in the following 3 groups: (1) BA+COPD: Patients diagnosed with asthma complicated with COPD on the basis of smoking history and laboratory findings. (2) COPD+BA: Patients diagnosed with COPD complicated with asthma on the basis of response to treatment. (3) COPD: Patients diagnosed with COPD alone. Lung capacity, %FEV1 after β2-agonist inhalation, peripheral blood eosinophil count, and serum total IgE and antigen-specific IgE antibody levels as well as the presence of emphysematous lesions were analyzed. Results There were no significant age differences among the groups. %FEV1 and serum total IgE level in the BA+COPD group were significantly higher than those in the COPD group. The percentage of patients with positive specific IgE antibodies for more than one antigen was 78%, 57%, and 52% in the BA+COPD, COPD+BA, and COPD groups, respectively. Positive rates were higher in the BA+COPD than in the COPD group for house dust, a tick, a cockroach, a midge, and a moth, and higher in the COPD+BA than in the COPD group for house dust. Positive rates for Candida and aspergillus were similar among groups (approximately 20%). Conclusion An asthmatic patient with dyspnea may be diagnosed with COPD. I suggest that environmental antigen sensitization may occur in the atopic factor-positive COPD patient with age, and that the possibility of complicating asthma must be considered. Methods This is a cross-sectional study which was conducted during pilgrims seasons during hajj year of 2011 and 2012. Results Ninety-seven COPD patients were identified and subsequently recruited to this study. The proportion of AECOPD during Hajj 2011 and 2012 was 48% (n = 47). General characteristics of the subjects were as follows: elderly (53%), not current smokers (53%), with co-morbidity (55%), having suffered from acute respiratory tract infection (98%) and moderate COPD severity (83%). In the bivariate and multivariate analyzes found significant relationship between acute respiratory tract infection and comorbidity factors on the incidence of AECOPD. Conclusion This study found a high proportion of AECOPD in Jakarta Embarkation pilgrims. We found Significant relationship between acute respiratory tract infection and comorbidity factors on the incidence of AECOPD. Key Words Acute exacerbation of COPD, Pilgrims of Jakarta Embarkation. MORIHIRO TAJIRI, TOMOTAKA KAWAYAMA, TAKASHI Background and Aim of Study Acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) is considered to be a nearly fatal condition during the clinical course of IPF, as it is unresponsive to most conventional therapies. The aim of this study is to evaluate the efficacy of recombinant human soluble thrombomodulin (rhsTM) for AE of IPF.

We conducted a retrospective study of IPF cases who developed AE and were treated with corticosteroids (CS) combined with rhsTM. The subjects in the rhsTM-treated group comprised 15 patients with a mean age of 72.3 years. The clinical features and prognosis of the rhsTMtreated group was compared to those of the control group consisted of 25 IPF patients who had developed AE but not received rhsTM. Results CS pulse therapy followed by CS maintenance treatment were conducted in all cases after the onset of AE. Patients in the rhsTM-treated group received combination therapy of CS and a rhsTM (380 IU/kg for 30 min, iv. once daily) for 6 days. Two-months survival after the onset of AE is 93.3% in the rhsTM-treated group and 24.0% in the non-rhsTM-treated group (p < 0.001) The median survival after the first onset of AE was 308.3 days in the rhsTM-treated group and 137.7 days in the non-rhsTM-treated group. Therefore the prognosis of the rhsTM-treated group therefore was significantly better than that of non-rhsTM-treated group. Conclusions This study indicate that rhsTM combined with CS therapy may have beneficial effect in patiants with AE of IPF. Rationale Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic, and fatal lung disease without proven beneficial therapy. Recently pirfenidone (5-methyl-1-phenyl 2-[1H]-pyridone), an anti-inflammatory, antioxidant and antifibrotic agent, has been demonstrated to improve clinical course of IPF in several clinical trials. However, the time beginning pirfenidone for the therapy is still unclear and controversial. Thus, objective of this study is to investigate the clinical feature of patients with IPF, who were treated with pirfenidone for more than 6 months. Methods This study was done retrospectively to investigate 11 patients with IPF or usual interstitial pneumonia (UIP) with connective tissue disease (CTD), except for case of acute exacerbation. All patients were required for definitive or probable UIP pattern in high-resolution computed tomography in accordance with the international consensus statement. Ten patients with IPF and 1 patient with CTD were treated with pirfenidone (1200 mg/day) and compared several indices as follows, severity, pulmonary function test (PFT), oxygen saturation by pulse oximetry (SpO2), and serum KL-6 levels, between baseline and treatment at 6 months. Results At baseline, age and restrictive disorder in PFT of patients were older and more severe, respectively, than previous studies. At 6 months of treatment, there were no alteration in vital capacity (VC) (from 1905.0 ± 477.9 mL to 1994.0 ± 608.5 mL, %VC (from 58.4 ± 12.1 to 59.2 ± 16.6), severity, SpO2, and KL-6 levels (from 1448.8 ± 756.0 U/mL to 1322.3 ± 776.4 U/mL) from baseline. However, comparing alteration in the indices in term between 6∼9 months before and 6 months after baseline, pirfenidone attenuated progression of restrictive disorder in PFT and elevation of KL-6 levels. One patient was improved from 4 to 1 of severity. No serious adverse events were seen. Conclusion Treatment with pirfenidone may stabilize and improve clinical course of IPF when the introduction is done earlier.

There are little data on the effect of interval exercise in patients with interstitial lung disease (ILD). The aim of this study was to evaluate the feasibility and the effectiveness of interval exercise (IE) on the exercise capacity in patients with ILD. Methods Patients with ILD completed a four weeks of in-patient pulmonary rehabilitation (PR) at Tosei General Hospital from January 2005 to December 2012 were recruited. All patients first were recommended to enroll in the constant load exercise (CLE) group, and patients who could not perform the CLE protocols participated in the IE group. IE protocols were 30 second work periods interspersed with 30 second rest periods for 40 min/day. Patients who can carry out CLE (CLE group) exercised for 20 min/day. Target intensity was > 80-100% of baseline peak work rate in the IE group, and 80% in the CLE group.All patients evaluated the pulmonary function tests, 6 minute walk distance (6MWD), constant work rate test, quadriceps force, baseline dyspnoea index (BDI) on baseline and after PR program. Results Twenty-seven ILD patients (CLE in 12, IE in 15) were studied. After PR program, 6MWD increased significantly compared with baseline value both in the IE group (from 291. In-patients PR program were recommended because they could not perform outpatient PR program. A four weeks in-patient PR program consisted of high intensity exercise training(60-80%peak work rate) using cycle ergometer. In addition, they also performed resistance training. Dyspnea (Baseline dyspnea index : BDI),quadriceps force,exercise capacity (6-min walk distance: 6MWD) and health related QOL (SGRQ) were measured at baseline and after four weeks of PR. Results Twenty-eight IPF patients (19 males; 69 ± 8 years of age; FVC % predicted, 53 ± 17%; DLCO % predicted, 31 ± 15%) were studied. Following PR, significant improvements were observed in BDI (3.6 ± 1.9 to 4.2 ± 2.1, p = 0.001), quadriceps force (67.5 Nm ± 21.0 Nm to 71.7 Nm ± 24.2 Nm, p = 0.007), 6MWD (300.9 m ± 129.7 m to 327.4 m ± 149.0 m, p = 0.028), and SGRQ Total (69.8 ± 11.5 to 64.3 ± 15.2, p = 0.014). Conclusion In-patient PR program improved dyspnea, quadriceps force and exercise capacity and HRQOL in patients with advanced stage of IPF.

Background and Aim of Study Although a 30-second chair stand test (CS-30) has been used as a measurement test for assessing the strength of lower extremities in adults, the usefulness in interstitial lung disease (ILD) is unknown. The aim of this study was to elucidate the usefulness of a CS-30 in mild-to-moderate ILD. Methods Nineteen consecutive patients with ILD who underwent a 6-min walk test (6MWT) and CS-30 as evaluations in clinical practice were included (17 of idiopathic pulmonary fibrosis and 2 of connective tissue disease related ILD). The data was reviewed retrospectively and a comparison was made between 6MWT and CS-30. Results Of 19 patients, 15 were male. The age was 73 ± 9 years old. The modified Medical Research Council (MRC) dyspnoea score was 2.3 ± 0.7. The PaO2 was 87 ± 13 Torr. The percent predicted FVC, TLC, and DLCO were 80 ± 16%, 78 ± 14%, and 70 ± 22%, respectively. The 6MWT data was as follows; walk distance (6MWD): 450 ± 101 m, maximum heart rate (HRmax): 118 ± 17 bpm, maximum respiratory rate (RRmax): 42 ± 8 bpm, minimum SpO2 (SpO2 min): 87 ± 6%, and maximum modified Borg dyspnoea score (MBSmax): 6.4 ± 1.6. In contrast, the CS-30 data was as follows; number of times (CS-30T): 16 ± 4, HRmax: 103 ± 15 bpm, RRmax: 31 ± 5 bpm, SpO2 min: 92 ± 4%, and MBSmax: 4.7 ± 1.2. In comparison of these parameters between the two tests, the CS-30T was significantly correlated with the 6MWD (ρ = 0.80, P < 0.001). However, the HRmax, the RRmax, and the MBSmax were significantly lower (P < 0.001, P < 0.001, and P < 0.001, respectively) and the SpO2 min was significantly higher (P < 0.001) in the CS-30. The number of patients who desaturate severely (SpO2 min < 85%) was significantly smaller in the CS-30 (2 vs 6, P = 0.04). The decrease in SpO2 during the tests was significantly smaller in the CS-30 (5.1 ± 2.5% vs 9.9 ± 4.5%, P < 0.001). Conclusion The CS-30 is a useful test to evaluate exercise capacity in patients with mild-to-moderate ILD because of its alleviated desaturation.

Background Forced oscillometry is a non-invasive method to measure respiratory resistance and reactance. In this study, we investigated the characteristics of resistance and reactance obtained with an impulse oscillation system (IOS) in patients with idiopathic pulmonary fibrosis (IPF). Method IOS and spirometry were performed in 35 IPF patients, 40 chronic obstructive pulmonary disease (COPD) patients, and 27 healthy volunteers. Respiratory resistance and reactance were assessed as measurements averaged over several tidal breaths (whole-breath analysis) and as measurements separately averaged during inspiration and expiration (inspiratory-expiratory analysis). Results Whole-breath IOS analyses in IPF patients showed increased resistance at 5 Hz (R5) and decreased reactance at 5 Hz (X5) compared with controls, although these features were also found in the COPD groups. However, the changes in X5 between inspiration and expiration were found to vary between IPF and COPD groups. Expiratory X5 was more negative than inspiratory X5 in COPD patients. In contrast, inspiratory X5 was found to be more negative than expiratory X5 in IPF patients. In IPF patients, within-breath changes in X5 (deltaX5), defined as expiratory X5 minus inspiratory X5, was significantly higher than those in the other groups. Furthermore, deltaX5 was inversely correlated with vital capacity, diffusing capacity of carbon monoxide and composite physiologic index (CPI) in IPF patients. Conclusions This study suggests that an increased X5 magnitude during inspiration compared with that during expiration is a characteristic feature of IOS measurements in IPF patients, which is clearly different from those in COPD patients. This within-breath X5 change in IPF might be associated with its severity and physiological abnormality, although further studies are needed to investigate its cause. Aim The aim of the study is to investigate the clinical feasibility of the quantification of lung perfusion blood volume (PBV) and xenon ventilation by dual-energy CT in differentiation of patients with combined pulmonary fibrosis and emphysema (CPFE) associated with idiopathic pulmonary fibrosis (IPF) and IPF alone. Subjects and Methods Seventeen CPFE patients (12 males, 5 females; mean age, 74.9 years) and 17 IPF alone patients (12 males, 5 females; mean age, 75.4 years) underwent dual-energy CT (SOMATOM Definition; Siemens Healthcare, Forccheim, Germany) during April 2012 and March 2013. The subjects inhaled 35% stable nonradioactive xenon to take a single deep breath. After performing xenon ventilation CT, intravenous injection of contrast material was administered. Xenonenhanced and pulmonary CT angiographic images were derived by using threematerial decomposition technique. Furthermore, the percentage of areas enhanced by xenon and adjusted PBV CT values were calculated in the upper, middle, and lower lung fields relatively by the following formulae: volume enhanced by xenon gas/ volume of each lung field x 100 and PBV CT value/enhanced CT value in pulmonary artery x 100. Results The percentage of areas enhanced by xenon in both lungs calculated as CPFE/IPF = 71.9 ± 15.8%/77.5 ± 13.5% relatively. In particular, the percentage of areas enhanced by xenon in upper predominant defect pattern of CPFE was significantly higher than that in diffuse defect pattern of CPFE. The honeycomb lesions in IPF alone showed significantly increased the percentage of areas enhanced by xenon/adjusted PBV CT values ratio compared with those in CPFE. In addition, the ratio of each lung field in diffuse defect pattern of CPFE was more decreased than that in IPF alone. Conclusions Quantification of lung perfusion blood volume and xenon ventilation by dual-energy CT is feasible for differentiating of patients with CPFE and IPF alone. Background Lymphangioleiomyomatosis (LAM) is a progressive rare lung disease that exclusively affects women of childbearing age. Recent studies have revealed that measurement of serum vascular endothelial growth factor (VEGF)-D level is useful for the diagnosis of LAM. Serum VEGF-D level may serve as a biomarker of disease severity, disease progression, or treatment response in LAM. In this study, we analyzed patients of LAM retrospectively.

We analyzed 87 sporadic LAM (38.4 (22.5-64.2) years old) and 13 TSC-LAM Patients (36.7 (25.2-58.4) years old) retrospectively in this study. There are 7 patients who underwent lung transplantation and 7 patients passed away. One patient was overlapped between lung transplantation groups and passed away group. Serum proteins levels were evaluated with clinical data by using multivariate analysis. Results Seven patients passed away because of respiratory failure and one patient by severe seizure attack. These patients were complicated with pneumothorax, chylothorax, angiomyolipoma, lymphatic diseases, and so on. Patients with the history of treatment with gonadotrophin-releasing hormone analogues (n = 8) and/or sirolimus (n = 5) were included in these patients. Median age of onset and first medical examination were 29.0 and 34.9 years old, respectively. The age of death in this 14 cases (lung transplantation and passed away) were 41.0 (32.0-57.3) years old, and life expectancy after diagnosis was 4.4 (0.3-14.9) years. And 5 years survival rate after visiting our hospital was 92 %. Among biomarkers, serum VEGF-D was the most sensitive biomarker for monitoring the prognosis compared to KL-6, SP-D, SP-A and ACE. Furthermore, serum VEGF-D level decreased immediately with sirolimus treatment. Conclusion LAM is a systemic disease with the poor prognoses. Serum VEGF-D level is useful biomarker for clinical diagnosis but not enough for prognosis factor of LAM. However, serum VEGF-D level is a good indicator of mTOR treatment.

Background The pathologic findings of chronic hypersensitivity pneumonitis (CHP) have many varieties of patterns, and often present UIP patterns. Therefore the distinction of CHP presenting UIP pattern (CHP-UIP) from idiopathic pulmonary fibrosis (IPF) is often difficult. The purpose of this study is to clarify high-resolution CT (HRCT) findings that can be useful to differentiate CHP-UIP from IPF. Method This study included 50 patients with CHP-UIP and 48 patients with IPF. Two groups of observers independently assessed the HRCT findings, evaluated the extent of each abnormal CT finding, and then made a first-choice diagnosis. When the diagnosis was CHP-UIP, they noted what was inconsistent with IPF. Results Correct diagnoses were made 78-80% in CHP-UIP, and 52-54% in IPF. There was no difference in the extent of ground-glass opacities, consolidation, honeycombing, and emphysema of both groups. The features that best differentiated CHP-UIP from IPF was excess of micronodules (hazard ratio 12.0 (95% CI;2.2-65.4), p = 0.004). Conclusion Although HRCT findings of CHP-UIP closely resemble to those of IPF, the excess of micronodules in HRCT can be useful finding to differentiate CHP-UIP from IPF. 

The goal of this study was to clarify the characteristics of pulmonary manifestation in patients with SS. Methods We reviewed patient with SS admitted to our hospital from 2007 to 2011, and retrospective analysis was performed. Results We had 37 patients with SS including 26 primary (pSS) and 11 secondary Sjögren's syndrome (sSS). Only 11 patients had mucous membrane drying symptoms. Anti-SSA and SSB antibodies in serum were positive in 32 and 13 patients, respectively. Thirty three patients had consistent findings of fluorescent dye examination and/or lip biopsy with SS. Interstitial pneumonia (IP) was the main pulmonary manifestation, and 10.2% of IP patients with unknown etiology on admission were diagnosed as having SS by careful clinical evaluations. Histopathological analysis revealed a variety of histological findings such as non-specific IP, and cellular bronchiolitis. Grand glass attenuation was the major HRCT pattern with lower and peripheral predominant distributions, and analysis of bronchoalveolar lavage fluid showed increase number of lymphocytes and neutrophils. Five-year survival rate was about 80%, and prognosis in patients with pSS seemed to be better compared with sSS patients. Conclusions IP is the major pulmonary manifestation of SS, and prognosis of SS patients with pulmonary diseases is not so poor. However, for more understanding of this disease, careful clinical evaluations including lip biopsy are necessary even for patients without sicca symptoms because of under-diagnosis of SS. Riluzole has recently become the first drug proven effective in the treatment of amyotrophic lateral sclerosis (ALS). We report two rare cases of lung injury caused by riluzole therapy in patients with ALS. Chest radiographs showed bilateral lower lobe, dorsal-dominant ground glass opacity and/or consolidation. A drug lymphocyte stimulation test (DLST) of peripheral blood or of bronchoalveolar lavage cells was positive for riluzole. Histopathological examination of lung biopsy specimens revealed lung injury without fungoid granuloma, vasculitis, or diffuse alveolar damage. To the best of our knowledge, this is the first report of riluzole-induced lung injury with a positive DLST results. Sarcoidosis and Crohn's disease are both granulomatous disorders and in some cases thought to be a different spectra of the same disease. Crohn's pulmonary manifestations are mostly drug induced eosinophilic pneumonia, fibrosis and subclinical pulmonary function abnormalities. Some case reports indicated that anti-TNF therapy can paradoxically cause sarcoidosis-like reactions. Our case is a 49 year-old white man who had been suffering from crohn's disease for 6 years and had needed tumour necrosis factor-alpha (TNF-α) treatment for perianal pericecal fistula. In routine control for anti-tnf treatment thorax CT scan showed centrale ground glass pulmonary infiltrates and a nodule in left apicoposterior segment. Bronchoalveolar lavage mycobacterial and bacterial cultures were negatif so we started isoniazid prophylaxis with infliximab therapy. After three months control torax CT scan showed regression of infiltrates. The patient had no respiratory complaints so follow-up was planned. After two years due to new infiltrates in X-ray, a new CT showed bilateral tree-in-bud and pulmonary infilitrates and mediastinal lymph nodes of 8 × 13 mm. Tracheal aspiration culture was negative for tuberculosis so with nonspecific antibiotherapy infliximab treatment continued. Control CT scan showed regression in left lung fields and new infiltrates in right lung fields. Neither eosinophilia nor any specific antibodies were found in the peripheral blood. Alveoler lavage revealed CD4/CD8 ratio of 9,2. In our case there is a diagnostic confusion about pulmonary infiltrations, mediastinal lymph nodes and alveoler lavage results. Crohn's disease alone can immitate sarcoidosis in bronkoalveoler lavage or can be concominant with sarcoidosis. In addition anti-TNF therapy can paradoxically cause sarcoid-like granulomatosis. The clinical discussion is whether withdraw infilximab therapy or to continue followup because the patient is asemptomatic and has no pulmonary function loss. Background and Objective An effective treatment has not been established for rapidly progressive interstitial pneumoniae (RPIP) and outcomes are poor. Furthermore, the predictive factors for prognosis are unkown. The aim of the present study was to assess the clinical and radiological characteristics, and the prognostic predictors for survival in RPIP. We have defined RPIP as interstitial lung disease presenting as acute respiratory failure, with bilateral infiltrative shadows on chest high-resolution CT (HRCT), and unrelated to chronic respiratory disease or alternative causes of interstitial pneumonia due to underlying diseases. Study Subjects and Methods Fifteen RPIP patients (male:11, female:4) with a mean age of 69.9 years were studied retrospectively. All patients were treated at our institution in the period August 2007 to September 2012. We compared the clinical features and HRCT findings between 4 survivors and 10 non-survivors. In addition, we have assessed the prognostic predictors for survival during 60 days after the onset of RPIP. Results Here were no significant differences between survivors and nonsurvivors in age, sex, P/F ratio (110+−99 v.s 169+−85), serum KL-6, serum SP-D, APACHE score (11.2+−1.6 v.s 12.6+−4.7), lung injury score (3.3+−1.3 v.s 2.7+−1.1) and the therapeutic regimen and ground-glass attenuation, consolidation, honeycombing on HRCT. The HRCT findings such as architectual distortion and traction bronchiolectasis were more extensive in non-survivors than those in survivors. Ten of 15 (66%) patients died due to progression of RPIP during hospitalization. The median survival period was 838.6 days in survivors and 21 days in non-survivors. Conclusions lthough the mortality of patients with RPIP is high, long-term survival can be expected in patients who recovered from the status of refractory respiratory failure. HRCT findings were potentially helpful for predicting the prognosis in RPIP. Rapidly progressive interstitial pneumonia (RPIP), which is resistant to therapy and have a poor prognosis, is occasionally accompanied by clinically amyopathic dermatomyositis (CADM). Effective treatment of RPIP associated with CADM has not yet been determined. The anti-CADM-140 antibody is frequently detected in RPIP associated with CADM, and thought to be a useful serological marker. In addition, the serum ferritin level is thought to predict disease activity and prognosis. We encountered two Japanese patients with RPIP accompanied by anti-CADM-140 antibody positive CADM. These patients complained of fever, rapidly progressive dyspnea and characteristic cutaneous manifestations (Gottron sign, heliotropic rash and mechanic's hand), but mild muscle weakness. Chest high resolution computed tomographic scans (HRCT) revealed reticular opacities and air-space consolidation in both lungs with basilar predominance. The serum ferritin levels were elevated in both patients. The diagnosis of RPIP accompanied by CADM was made clinically. Intensive therapy was initiated with pulsed methylprednisolone, followed by high-dose oral administration of prednisolone, pulsed cyclophosphamide, and cyclosporine immediately. At early time point, high-dose intravenous immunoglobulin (IVIG) and direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) were also administrated. This intensive combined therapy rescued the two patients without respiratory failure. Chest HRCT image and pulmonary function test gradually improved, and the anti-CADM140-antibody titers and serum ferritin levels decreased in parallel. Early intensive therapy including IVIG and PMX-DHP could be an effective therapy for life-threatening RPIP associated with CADM. Background Inflammatory cytokines have been reported to play important roles in the pathogenesis of interstitial lung diseases. However, their individual roles in idiopathic interstitial pneumonitis (IIP) and in the other types of interstitial pneumonitis (IP), including collagen vascular disease associated interstitial pneumonitis (CVD-IP), remain unknown. In this study, we measured the bronchoalveolar lavage (BAL) fluid levels of several cytokines in patients with IIP and CVD-IP. Methods Cell subpopulations in BAL fluid were counted, and BAL fluid levels of IL-2, -6, -7, -8, -17, IFN-gamma, TNF-alpha, and TGF-beta1 were measured using a bead suspension array or an enzyme-linked immunosorbent assay (ELISA) kit in 16 patients (8 men, 8 women) with idiopathic nonspecific interstitial pneumonitis (NSIP), 5 patients (3 men, 2 women) with idiopathic usual interstitial pneumonitis (UIP), 5 patients (3 men, 2 woman) with rheumatoid arthritis in CVD-IP (RA), and 5 patients (3 man, 2 women) with dermatomyositis in CVD-IP (DM), and 13 patients (3 men, 10 women) with sarcoidosis. Results BAL cell subpopulations had high amounts of lymphocytes in NSIP and sarcoidosis, and neutrophils in RA. Levels of IL-7 were significantly higher in DM than in RA. IL-7 in DM was significantly correlated with lymphocytes. The levels of TNF-alpha were highest for RA, compared with other IPs, and sarcoidosis. In addition, the levels of IL-17 were highly detectable in RA, but not in NSIP, UIP, or sarcoidosis. Conclusions Differences in the cell types of BAL fluid and the level of each cytokine between patients with IIP and CVD-IP might reflect pathogenesis and be useful for diagnosis.

Introduction Leukostasis is a fatal complication in leukemia. Brain and lung are most commonly involved organs in leukostasis. In the lung, the clinical presentation similar to acute respiratory distress syndrome (ARDS). Being a medical emergency, early recognition of leukostasis and initiation of therapy prevents mortality. Result All of 3 patients in this article we disscussed had been diagnosed with chronic myelocytic leukemia (CML) before. They came to hospital emergency department because of dyspneu. From blood count, all of the patients got hyperleukocystosis, with leukocyte count 576.000/mm 3 , 308.000/mm 3 , 380.000/ mm 3 , respectively. All expertised of X-ray by radiologist were the same result: lung infiltrates. From blood gases analysis, first patient has SaO2: 45,9%, PaO2: 28,6 mmHg, AaDO2: 117,4 mmHg; second patient has SaO2: 65,1%, PaO2: 23,1 mmHg,AaDO2: 115 mmHg; third patient has SaO2: 76,6%, PaO2: 56,5 mmHg, AaDO2: 114,9 mmHg. They all were asssesed as lung leukostasis. First patient underwent a fine needle aspiration and the histological result was leukemic cells (myeloblast and mylocyte) infiltrated in lung. After they had been gotten cytoreduction (leukapheresis and hydroxyurea) they clinically and labolatory got better. Conclusion Although hydroxyurea and leukapheresis have been proposed to rapidly reduce leukocytes count and possibly related symptoms, few data support their true value in decreasing early mortality. In absence of specific guidelines for the management of symptomatic hyperleukocytosis such as lung lekostasis, leukapheresis when feasible, should be considered in the day-to-Introduction We had mainly used monopolar electric scalpel though heat diffusion by this instrument might have possibility to mistakenly damage surrounding tissue and vessels. In addition, during the operation of thoracoscopic thymectomy, it was difficult to choose what device should be used because of its narrow working space. Introduction of bipolar tissue sealing system has made a great progress and solve these problems.

We have mainly used ENSEAL TRIO it can control heat diffusion into lateral tissue that enables safe manipulation in the area neighboring blood vessels and nerves; it can appropriately seal tissue with even and high compression through the entire length of the jaw; it can seal and cut the tissue with one motion; it can give better visualization and manipulation in narrow operative field with its curved jaw shape. Results ENSEAL TRIO experience of thoracoscopic thymectomy demonstrated high feasibility without operative method change, intraoperative side injuries, and postoperative complications.

Introduction Lymphangioleiomyomatosis is a rare pulmonary disorder characterized by proliferation of smooth muscle diffusely throughout the lung parenchyma. Most patients present during their reproductive years, and survival is generally less than 10 years. While pulmonary lymphangioleiomyomatosis (PLAM) in elderly patients is very rare and some cases have been sporadically reported, the pathophysiologic mechanism and epidemiology of PLAM in elderly patients is still unknown. We present our case and review all previously reported cases of PLAM in elderly patients, published since 1960. Three case reports and one review article, a total of 6 elderly patients with PLAM have been demonstrated, including our case which we report here. Case reportA 76-year old woman complained of dyspnea of exertion and cough for previous 5 years. Spirometry did not reveal restrictive ventilatory impairment, FEV1 was 1.36 L and forced vital capacity was 1.79 L (84.4% predicted). Chest computed tomography (CT) showed diffuse thinwalled cystic air spaces throughout both lungs. Video-assisted thoracic surgery (VATS) was performed, and microscopic findings of thin-walled cyst showed proliferation of smooth muscle cells. Immunohistochemical staining revealed that aSMA-antigen was positive, although HMB antigen was negative. She was diagnosed as PLAM. Results A total of 6 patients were included in the review of previously published cases. The age of the patients was 65 to 76 years. All patients were female. The most common symptoms on initial visit was dyspnea on exertion (5 of the 6, 83%). In terms of treatment, none received any hormone therapy. Two of the 4 patients (50%) survived. Conclusion PLAM could occur in elderly patients after menopause even if it is very rare. Physicians should consider PLAM if women present dyspnea of exertion despite they are in a postmenopausal state. The severity of PLAM in elderly women might be better than the one in menopausal women. Background Thymic carcinoma is a rare malignant tumor. No definitive chemotherapeutic regimens have been established in the advanced disease, especially in the second line setting, and thus its prognosis is still disappointing. The thymidylate synthase (TS) expression level in the thymic carcinoma were lower compared with lung squamous cell cancer, suggesting a potential sensitivity of thymic carcinoma to S-1. Methods We evaluated the efficacy and toxicity of S-1 monotherapy as salvage in three patients with relapsed thymic carcinoma from April, 2011 to July, 2013. The initial dose of S-1 was determined based on the body surface area (BSA), and the drug was taken orally twice daily for two weeks. Results One patient achieved partial response, whilst two patients had stable disease. Median progression-free survival time was 2.8 months in the three patients, one of whom obtained disease control in 17 months. Hematological toxicity was mild, whereas gastrointestinal toxicity and general fatigue were observed. Conclusion Oral S-1 monotherapy seems effective and safe in the salvage setting in patients with advanced thymic carcinoma. A multicenter phase II trial has been launched. A 61-year-old man was indicated by health check that serum CEA elevated, and visited other hospital. He was seen in our hospital because of suspect of intestinal pneumonia in chest CT scan,or other malignancy diseases. He had a history of colon cancer at age of 56 which was resected by endoscopic mucosal resection. He was suspected of recurrence of colon cancer. But, no findings suggestive of malignancy were obtained with total colon fiber scopy. Chest CT scan showed ground-glass pattern,thickened interlobular septa in both lower lobes. Blood exam showed elevation of KL-6, LDH. He had bronchoscopic examination with susupect of intestinal pneumonia. Bronchoalveolar lavage showed white turbidity as like as water that has been used to wash rice. Because Anti-GM-CSF autoantibody was significantly increased in serum and bronchoalveolar lavage,we diagnosed him as autoimmune pulmonary alveolar proteinosis. He had got outpatient treatment without worsening of respiratory status for about 6 months. Serum CEA is usually used as a marker of malignant disease. While it is reported that serum KL-6 followed by CEA are correlated with disease progress of autoimmune pulmonary alveolar proteinosis. In this case, we could diagnose him as pulmonary alveolar proteinosis by bronchoscopic examination with serum CEA elevation and serum other marker. Background and Aim of Study Pentraxin-3 (PTX3) is newly discovered inflammatory biomarker in various inflammatory conditions. This study was designed to measure plasma PTX3 levels in febrile neutropenia (FN) lung cancer patients and to examine its usefulness. Methods Consecutive 14 FN patients during chemo/chemoradiotherapy were enrolled. On the onset day (day1), plasma was taken and treatments for FN were started following guidelines. On the day3 and day7 plasma were also taken. As control subjects, 28 untreated lung cancer patients without infections and 48 healthy controls were enrolled and plasma was also taken on the enrolled day. We measured CRP and PTX3 levels by ELISA and examined its correlation with clinical parameters of FN in lung cancer. Results Plasma CRP levels on day1 in FN lung cancer patients (FN/LC, 8.11 ± 6.42) were significantly increased compared with those of healthy controls (HC) and chemo/chemoradiotherapy naïve lung cancer patients (CN/LC) (p < 0.05). However, CRP levels of CN/LC (0.27 ± 0.11) were significantly higher compared with those of HC (0.06 ± 0.06) (p < 0.05). In contrast, plasma PTX3 levels on day1 in FN/LC (6.14 ± 5.28) was significantly increased compared with those of HC and CN/LC (p < 0.05). PTX3 levels of FN/LC (0.80 ± 0.72) were not significantly higher compared with HC (0.77 ± 1.06). PTX3 levels in FN/LC reached a peak immediately in day1. However, CRP levels in FN/LC reached a peak slowly in day3. However, PTX3 levels in day7 and CRP levels in day3 were significantly correlated with fever period. Conclusion PTX3 has the potential to be a useful biomarker for FN in lung cancer patients.

Background Chest radiographic screening is a commonly used conventional method for the detection of lung and mediastinal tumors. However, more than half of the tumors detected by chest radiography are those that have already progressed to the advanced stage. Recent studies have shown that low-dose spiral computed tomography (CT) is effective for the early stage detection of lung cancer, and this facilitates better resectability and long-term survival. The present study was performed to evaluate the usefulness of chest radiography and spiral CT in the diagnosis of mediastinal tumors. Methods Approximately, 50000 consecutive asymptomatic individuals had undergone a health check-up at our institution from April 2012 to March 2013. Of these individuals, 44663 had undergone chest radiography or low-dose spiral CT. The presence of mediastinal tumors was investigated in these individuals. Results Four mediastinal tumors were detected (1 thymoma, 1 teratoma, 1 liposarcoma, and 1 neurofibroma with Recklinghausen's disease). One case was detected using both chest radiography and CT, whereas the other 3 were detected using chest CT only. In these 3 cases, no abnormal opacity was observed on chest radiographs. The tumors in all 4 cases were successfully resected, and to date, no tumor recurrence has been observed. Conclusion Thus, we propose that screening using low-dose spiral CT is more useful than chest radiography and might contribute to the early detection and treatment of mediastinal tumors. Background Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor associated with asbestos exposure with limited response to conventional therapy, so diagnosing MPM early is very important. We have previously reported that angiopoietin (Ang)-1 was correlated with bleomycininduced pulmonary fibrosis. Methods We investigated the association of Ang-1 with the development of MPM which originate from mesenchymal cells similar to lung fibroblasts. Results We demonstrated that Ang-1 stimulated the cell growth and migration of MPM cells in in vitro studies. We also demonstrated that patients with MPM had significantly higher serum levels of Ang-1 in comparison to a population who had been exposed to asbestos but had not developed MPM. The patients with advanced stage MPM showed higher levels of Ang-1 than the early stage MPM patients and the Kaplan-Meier method revealed a significant correlation between serum Ang-1 levels and survival. Conclusions We propose the possibility that Ang-1 plays an important role in MPM tumor growth and our data suggest that the serum concentration of Ang-1 could be useful as prognostic factor. 3 

Background/Aims Growth factors play a critical role in proliferation for a variety of cancer cells. The present study was conducted to understand the signaling cascades underlyingPDGF-D/PDGF-ββ receptor-mediated proliferation of mesothelioma cells. Methods Cell growthand cell cycle were analyzed in human non-malignant Met5A cells and malignant mesotheliomacells such as MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452 cells. Results Growth of allthe cells used here was not affected by PDGF-D, regardless of concentrations (1-30 ng/ml) ortreatment time (48-72 h). Spontaneous growth of those cells was significantly inhibited byknocking-down PDGF-D or PDGF-ββ receptor, without affecting cell cycling. The cell growth wassignificantly inhibited by the Akt inhibitor MK2206 and the ROCK inhibitor Y27632 for all the celltypes, by the PDK1 inhibitor BX912 for NCI-H28 cells alone, and by the Rac1 inhibitor NSC23766 for NIC-H2052 cells alone, while the PI3 kinase inhibitor wortmannin had no effect. The cellgrowth, alternatively, was significantly attenuated by MAP kinase kinase inhibitor PD98059 or theERK1/2 inhibitor FR180204 for all the cell types. Conclusion The results of the present studyshow that PDGF-D promotes mesothelioma cell proliferation by targeting ROCK or MAP kinasethrough autocrine activation of PDGF-ββ receptor.

Identifying the mortality risk of emergency patients is essential as a consequence of increasing number of admission with diverse severity of disease. Rapid Emergency Medicine Score (REMS) has been developed to predict the mortality of nonsurgical emergency patients and to help doctors in making clinical decision rapidly based on objective data. We evaluated the performance of REMS in predicting the mortality of nonsurgical emergency patients in Cipto Mangunkusumo Hospital (CMH), a tertiary referral center in Indonesia. Methods We performed a prospective cohort study on nonsurgical patients who attended to Emergency Department (ED) of CMH between October and December 2012. Age, body temperature, mean arterial pressure, heart rate, respiratory rate, peripheral oxygen saturation, and Glasgow coma scale were obtained at admission to calculate the REMS. The outcome was in-hospital mortality. Calibration was evaluated with Hosmer-Lemeshow test and discrimination was evaluated with area under the receiver operating characteristic curve (AUC). Results A total of 815 nonsurgical patients attended to ED during the study. As many as 741 (90.9%) patients were followed until the outcome occured. In-hospital mortality was observed in 145 patients (19.6%). Hosmer-Lemeshow test showed a good calibration (p = 0.665). The AUC of REMS was 0.77 (95% CI 0.723; 0.817). Conclusion Rapid Emergency Medicine Score is a good prognostic scoring system for adult nonsurgical emergency patients in Indonesia. Key Words: Rapid emergency medicine score, nonsurgical, mortality.

Objective We designed a prototype endotracheal tube with double cuffs and a small intercuff hole connected to a negative pressure port. The hypothesis of this study was that a negative pressure between double cuffs prevents fluid leakage past the double cuffs. Methods We obtained two cuffs from Standard endotracheal tubes and attached them to a tube (8.0 mm internal diameter (ID)). We made a 1 mmsized hole between the cuffs, which is connected to an external port for applying the negative pressure in the intercuff space. PVC trachea with a 20 mm-sized internal diameter was intubated with ETT. We spilled continuously the blue-dyed water on the upper cuff and applied a negative pressure in the intercuff space though the port for 10 minutes. And then we measured the volume of dripped water below the lower cuff. And the leakage tests were Background Streamlined Liner of the Pharynx Airway (SLIPA) is a disposable supraglottic airway. There are two strategies to select the size of SLIPA. This study compared the utility of two strategies in selecting the optimal size. Methods One hundred forty-two patients were randomly divided into two groups with size selection by height (H) and the maximal width of the thyroid cartilage (T). The investigator lifted the jaw and pushed the device until the heel lodged in the nasopharynx. And then, the investigator made note of the oropharyngeal leakage pressure (OLP) and the degree of insertion difficulty. In cases of an OLP under 15 cmH2O, the investigator manipulated the apparatus to try to properly position it. If air still leaked, another attempt was made using a SLIPA one size larger until an OLP over 15 cmH2O was achieved in up to three attempts. After insertion, the investigator measured the inspiratory and expiratory tidal volume (TVinsp and TVexp, respectively). Postoperatively, the presence of blood or regurgitated fluid on the device was evaluated. Results OLP for group T was higher than that of group H (P = 0.009). The need for manipulation and the leak fraction [(TVinsp-TVexp)/TVinsp] was higher in group H than in group T (P = 0.008 and 0.034, respectively). The degree of insertion difficulty, number of trials and incidence of blood and regurgitated fluid on the device were similar between the two groups. Conclusions The width of thyroid cartilage is a more appropriate strategy than patient's height for selecting the optimal SLIPA size. However, both strategies are clinically applicable. Background and Aim of Study The utility of tracheostomy to expedite weaning and prevent complications in patients with mechanical ventilation is suggested. The optimal timing of tracheostomy is debated and usually not a strong option to the patients and family in Taiwan, a culturally lowtracheostomy-rate country. The aim of this study is to build up the structured family meeting and determine its efficacy on the will of tracheostomy, rate of ventilator weaning, hospitalization length and mortality rate in patients with prolonged mechanical ventilation (PMV). Methods This retrospectively observational study is implemented from January, 2010 to March, 2013. Structured family meeting is built up and held to those who fulfill all of the following criteria: 1. Patients who were admitted to the respiratory care center (RCC), a subacute ventilator dependency setting, 2. Patients with endotracheal tube intubation and unwilling to receive tracheostomy in intensive care units (ICUs). Results A total of 102 patients were enrolled. 57.8% (59/102) patients were male and 42.2% (43/102) patients were female. 42.2% (43/102) patients underwent tracheostomy after implementation of structured family meeting. Patients who came from medical ICU is the only predictor of the will of tracheostomy (Odds ratio = 4.029; p = 0.013). Patients who underwent tracheostomy had longer RCC length and hospital length than patients with unwilling to receive tracheostomy (37.2 ± 18.2 v.s. 23.9 ± 16.3, p = 0.000; 71.5 ± 23.4 v.s. 58.7 ± 18.9, p = 0.003, respectively). The rate of ventilator weaning and mortality rate within one-month after discharge in patients who underwent tracheostomy were similar with patients with unwilling to receive tracheostomy (72.1% v.s 57.6%, p = 0.196; 11.6% v.s. 20.3%, p = 0.370, respectively). Conclusion The structured family meeting increased the will of tracheostomy in patients with PMV in a culturally low-tracheostomy-rate country.

Background and Aim of Study To discuss and analyse the correlation of the positive rate of common food allergen-specific immunoglobulin E (sIgE) with suspected food allergy patients in our hospital. Methods Using fluorescence enzyme-linked immunosorbent assay to detect the serum sIgE antibody of the patients, including 7 kinds of food allergens (milk, egg white, egg yolk, peanut, soy, shrimp and crab) from July 2006 to January 2013. Results 528 patients were detected milk and egg white sIgE, the positive rate of milk sIgE was 35.2%, the positive rate of egg white was 33.7%, 26.9% were both positive, R = 0.758(P < 0.01). 282 patients were detected egg white and egg yolk sIgE, the positive rate of egg white sIgE (59.6%) was much higher than the yolk sIgE (9.2%). The positive rate of the milk and egg white sIgE decreased with the age. The degree in level 4 or above of milk and egg white sIgE was only 0.4%in positive patients. We detected serum sIgE of shrimp and crab in 64 patients, 16 cases was positive of the shrimp, 17 cases of the crab was positive, both positive in 16 cases, R = 0.973 (P < 0.01). In the simultaneous detection of 34 patients' serum sIgE of peanut and soybean, peanut was positive in 4 cases, soybean was positive in 3 cases, both positive in 2 cases, R = 0.879 (P < 0.01). Conclusion Egg white is the major allergen of egg allergy. The relevance of shrimp and crab, peanuts and soybeans is extremely high, probably because of their homology; egg white and milk is not homologous food, but their positive rate has significant correlation, indicating the synergistic reaction. Background Tracheal web is a rare congenital abnormality of the trachea and is often misdiagnosed as refractory asthma. Mounier-Kuhn syndrome (MKS) is also a rare disorder characterized by a marked dilatation of the trachea and main bronchi, sometimes with diverticulosis and tracheobronchomalacia. However, the etiology is uncertain. Case Report 47-year-old woman referred to our hospital because of persistent cough and wheezing. She was diagnosed as asthma 10 years ago and had some episodes of pneumonia and 200 pack-year smoking history until 10 years ago. The pulmonary function tests showed a flat pattern of flow volume curve with marked limitation of peak flow. The chest CT scan revealed trachobronchomegaly (diameter, 67 mm) and web-like tracheal stenosis. The tracheal web obstructed almost 90% of the inside diameter of the trachea 5 cm below the vocal cords, although the collapse of the trachea on expiration was unclear. According to these evidences, this patient was diagnosed as MKS with tracheal web. Discussion Despite the congenital tracheal web, there were no asthmatic symptoms in infancy because the congenital dilation of trachea was present in birth. Tracheobronchomegaly in this case was due to a congenital abnormality rather than an atrophy of the connective tissue of trachea. Also, she gave birth safely to two children 25 years ago asymptomatically, and asthmatic symptoms appeared 10 years ago. It is considered that the web-like tracheal stenosis is in progress. The resection of this web might be considered to be a reasonable treatment. The lack of the significant tracheal collapse on expiration, which is one of the main features of MKS, might suggest the prevention of the tracheal collapse by the tracheal web in this case. Thus, the choice of the future treatment to her, should be made deliberately.

Smoking is associated with increased risks for various diseases. On the other hand, dementia becomes a social burden as an elderly population increases. The present study aimed to clarify relationships between smoking status and cognitive function in community-dwelling elderly men. Methods A comprehensive geriatric health survey of all residents, aged 65 years and over, of a village along the Sea of Japan was carried out between August and September 2012. Self-administered questionnaires were distributed by mail, and the subsequent responses were validated through home-visit and face-to-face interviews by trained interviewers who simultaneously performed the Mini-Mental Status Examination (MMSE). On the analysis, the subjects were divided into 3 groups, the current smoker, former smoker and non-smoker. The MMSE score was compared according to the smoking status and age. Results Of the 1103 subjects who participated in this survey (participation rate: 91.9%), 416 male subjects were analyzed. These were 93, 234, and 89 subjects in the current smoker, former smoker and non-smoker groups, respectively. The current smokers aged 80 years and over were the fewest (p < 0.001). The MMSE scores were not significant different among any smoking status and age groups. In the MMSE average scores, however, tendencies were found that current smoker aged < 70 and 70-79 years had the lowest compared to the former and never smokers, whereas those aged 80 years and over were the highest. Conclusion In this study we could not find any association between the MMSE scores and smoking status. Background Most video-assisted thoracoscopic surgery (VATS) requires general anesthesia with one-lung ventilation. According to our previous studies, thoracoscopic bleb resection (TBR) could be performed under low tidal volume (Vt), two-lung ventilation without any technical problem. Usually low Vt requires higher respiration rate (RR) to meet patents' metabolic needs, producing fast-moving operation field which is unfavorable. We evaluated the most feasible ventilator setting for TBR with low Vt in the respect of gas exchange. Methods Patients who received scheduled TBR were included according to inclusion and exclusion criteria. General anesthesia was provided and TBR was performed under two-lung ventilation with low Vt setting (5 ml/kg). RR was varied 15, 18 and 22 cycles/min according to protocol. Surgery was performed without CO2 gas insufflation. During anesthesia period, vital sign, arterial blood gas analysis (ABGA), values associated mechanical ventilation were monitored and recorded. Results Total 48 patients were finally included in statistical analysis. Operation and anesthetic time, number of used endoplate were not significantly different between 3 groups. There was no patient presented hypoxemia or hypercarpnia. Minute ventilation was significantly lowered in RR 15 group (P < 0.001), the results of ABGA were in physiologic range. Conclusion Tow-lung ventilation with low Vt and 15 cycles/min RR was acceptable for TBR even though decreased minute ventilation. With this ventilation setting, optimal surgical field was guaranteed and arterial blood gases were remained within normal range.

Asthma is chronic disease and numbers of asthmatic patients increase continually. Thailand has asthmatic patients more than four million. Mortality rate of asthmatic patients was 5% in each year and Public health of ministry has policy 3 D of service so Department out of patients of Buriram Hospital improved caring by teamwork of One Stop Service at the Adult Asthmatic Clinic by every service this hear altogether and teamwork has 12 development of activities. This study was descriptive research, studies result of caring 256 asthmatic patients who consistently admitted at the Adult Asthmatic Clinic during 1 January 2011 to 31 December 2012. Used statistics to the analysis were Paired t-test, percentage and mean. The results showed that Admittion decreased 60% and ER-visit decreased 62.50 %, peak flow expiratory rate more than 80% increased form 82.67% to 89.35% and significance by statistics, (p < 0.05). After One Stop Service was implemented, the averaged time spent at Adult Asthmatic Clinic decreased 1.04 hours, payment of caring decreased 89,853.50 bath and satisfaction rate was 94.25% and enlarge 23 hospitals networks where can take care asthma patient, so this caring was asthma controll, service convenient quickly, high satisfaction and decreased payment of caring, so this service should be cover other asthmatic patients who don't admitted in Asthmatic Clinic and especially the old patients or don't have care givers, so this service should be cover other chronic diseases example hypertension, stroke. Background Assessment of patients with pulmonary illnesses requires objective measurement. However not all areas have standard spirometry. Portable electronic spirometers have been developed, but need further evaluation. The objective of this study is to evaluate the handheld spirometer as a diagnostic tool in comparison to standard pulmonary function testing. Methodology A cross-sectional study conducted at the Philippine Heart Center. Patients 19 years old and above, who underwent standard pulmonary function testing were requested to undergo handheld spirometry upon return. Results were interpreted independently. Results A total of 395 subjects were included. There was a significant difference in the values of the FVC, FEV1 and FEV1/FVC between handheld spirometer and standard PFT (p 0.0001). However, there was good agreement between the two devices as to diagnosis of normal, obstructive and restrictive lung disease (kappa 0.984, p 0.008). There was also good agreement between the two devices as to classification of mild, moderate and severe for both obstructive (kappa 0.839 + 0.044) and restrictive lung disease (kappa 0.898 + 0.028). The handheld spirometer was noted to be accurate in diagnosing obstructive lung disease (kappa 1.0, sensitivity 100%, specificity 100%, PPV 100%, NPV 100%), but slightly less accurate in diagnosing restrictive lung disease (0.968, sensitivity 97.9%, specificity 100%, PPV 100%, NPV 95.9%).

Conclusion The values of FVC, FEV1 and FEV1/FVC obtained using the handheld spirometer may vary significantly from standard PFT, but the handheld spirometer can diagnose normal, restrictive and obstructive lung disease, and classify disease severity as to mild moderate and severe, with good agreement with standard PFT. The handheld spirometer was found to be accurate in diagnosing obstructive lung disease and slightly less accurate in diagnosing restrictive lung disease. It may substitute the use of standard spirometry in areas lacking standard PFT and for patients with difficulty ambulating.

The radical cure treatment of lung cancer is a surgical operation. The evaluation of a postoperative pulmonary function is important for estimating the risk of complications and long-term disability after pulmonary resection, especially for elderly patients. Number of segments method is often used to estimate the predicted postoperative pulmonary functions. However, that method does not consider the actual volume of resected lobe. Currently, 3D-CT can divide and calculate the lung volume for every lobe. The aim of this study is to reveal the differentiation between 1) actual values examined after lobectomy, 2) estimated postoperative values calculated with traditional number of segments method, and 3) estimated postoperative values calculated with resected lobular volume obtained by 3D-CT on FEV1.0 (PO FEV1.0, ePOseg FEV1.0, ePOCT FEV1.0), predicted FEV1.0 (PO %FEV1.0, ePOseg %FEV1.0, ePOCT %FEV1.0) and predicted DLco (PO %DLco, ePOseg %DLco, ePOCT %DLco), respectively. Methods We calculated the lobar volume and the emphysematous lobar volume < −950 HU of each lobe using slice-by-slice method with Zaiostation2 ® software program. Results 8 patients were enrolled for this study (mean age 71.9 years). All patients were classified into GOLD2, and were diagnosed as adenocarcinoma (2 patients), squamous cell carcinoma (3) and non-small cell lung cancer (2) . Both PO FEV1.0 and ePOCT FEV1.0 are significantly larger than ePOseg FEV1.0, but, there is no statistically significant between PO FEV1.0 and ePOCT FEV1.0. There is no significantly difference between ePOseg %FEV1.0. and ePOCT %FEV1.0, and those are significantly smaller than PO %FEV1.0. There is no significantly difference between ePOseg %DLco. and ePOCT %DLco, and those are significantly smaller than PO %DLco. Conclusion In COPD patients with moderate air flow limitation, the predicted postoperative pulmonary function calculated with number of segments method or 3D-CT might be underestimated compared with actual measurement. Conclusions In this study, lower BMI, the presence of SVC syndrome and the presence of anemia were poor prognostic factor for survival.

Background It is reported that EGFR mutation is frequent in non small cell lung cancer (NSCLC) patients who are presenting with miliary intrapulmonary carcinomatosis. We often encountered disseminated carcinomatosis as well as intrapulmonary carcinomatosis. This study aims to investigate the clinical characteristics of patients with miliary intrapulmonary or disseminated carcinomatosis. Methods Patients with advanced NSCLC who harbor EGFR mutation and presented with miliary intrapulmonary or disseminated carcinomatosis were enrolled respectively, from September 2005 to January 2011. EGFR mutations in exons 18-21 were confirmed by pyroseqeuncing method after genomic DNA was extracted from paraffin-embedded tissue specimens. Clinical characteristics, responses to treatment and outcome were collected from medical records. Results The most frequent mutation was in-frame deletions in exon 19 (68.7%). A L858R and G719A were detected in 19 (29.7%) and 1 (1.7%) patient, respectively. Patients with miliary intrapulmonary or disseminated carcinomatosis were more common in female (80.0% vs. 55.1%), non smoker (80.0% vs. 53.1%), and 19 deletion mutation (86.7% vs. 63.3%), however there were no significant difference statistically. They showed relatively shorter PFS to EGFR TKIs (median 9.7 vs, 12.8 months) and poorer overall survival (median 15.9 vs. 29.0 months) compared to patients without miliary metastasis. In multivariate analysis, higher metabolic tumor volume (MTV) in PET-CT was confirmed to be an independent predictor of shorter OS, when considered together with stage, gender and smoking status. Conclusions The data indicate that NSCLC presenting miliary intrapulmonary or disseminated carcinomatosis were more common in female, adenocarcinoma, non-smoker and 19 deletion mutation was comparatively frequently detected, however there were no statistically significant differences. PFS to EGFR tyrosine kinase inhibitors and overall survival was less in patients with miliary intrapulmonary or disseminated carcinomatosis compared to patients without miliary metastasis. Poor clinical course might be associated with high tumor burden represented by MTV or total lesion glycolysis. Introduction The aim of this study was to evaluate the recent epidemiology of lung cancer in a tertiary referral hospital of South Korea. Methods Consecutive patients, who were newly diagnosed as lung cancer from June 2011 to December 2012 in Seoul National University hospital, were included in this retrospective study. The clinical and pathologic characteristics were reviewed. Results All 979 of newly diagnosed lung cancer patients were included. The mean age at diagnosis was 65.6 ± 10.2 years old and 652 (66.6%) were males. Among 979 patients, 349 (35.6%) were never-smokers. In non-small cell lung cancer group (n = 887), stage IV was the most common (326, 36.8%). Adenocarcinoma was the major pathologic diagnosis (555, 56.7%). Compared to the data of previous national surveys, the proportion of adenocarcinoma was increasing from 30% in 1997 and 36.1% in 2005. The clinical characteristic of the patients with adenocarcinoma showed younger age (63.7 vs. 68.1, P < 0.001), predominance in female (P < 0.001), never smokers (P < 0.001), better performance status (P < 0.001) and early stage (P = 0.005). Conclusions The proportion of the lung adenocarcinoma has been increasing.

Introduction Lung cancer is one of the common causes of cancer death. End of life care in advanced cancer patient would be needed. Admission to intensive care unit (ICU) in patients with cancer would make some distress in emotion and quality of life. The decision making is difficult to admit ICU in lung cancer patient. The predictive factors of outcome will be needed. We reviewed the clinical outcome and characteristics of patients with lung cancer who admitted ICU retrospectively. Methods We retrospectively collected clinical data of patients with lung cancer who admitted ICU from January 2010 to November 2011. Causes of admission, use of mechanical ventilation, presence of do-not-resuscitate, mortality were included. Postsurgical care was excluded in analysis. Results One hundred thirty one patients were admitted in ICU. For postoperative care ninety three patients were admitted in surgical ICU and excluded. We analyzed thirty eight patients of lung cancer. NSCLC patients were 34 (89%) and SCLC patients 4 (11%). 25 patients (66%) were inoperable stage (stage IIIB, IV). Causes of admission were acute respiratory failure (78%), cardiovascular disease (8%), gastrointestinal bleeding (8%) and neurologic disease (5%). The mortality of ICU was 53% (20/38). Seventeen patients and family noticed the code of do-not-resuscitation after ICU admission. Twenty nine (79%) patients were received mechanical ventilation and 25 of 29 patients were dead during ICU care. Conclusion In advanced lung cancer patients, ICU care would not be needed in some conditions. The model of ICU mortality in lung cancer should be established for the purpose of well-dying care.

Introduction Incidence of lung malignancy is rising due to prevalence of smoking. Adenocarcinoma is the most common histological subtype worldwide and in Malaysia. Its treatments have evolved from the conventional chemotherapy to targeted therapy. EGFR mutation is an established predictive factor for the use of tyrosine kinase inhibitor (TKI). While EGFR mutation has been more commonly associated with Asians, its prevalence among different ethnic group among Asians has not be established. Methods A retrospective study. All patients seen in respiratory unit between Nov 2011 to Feb 2013 whom were suffering from lung malignancy were included. Their characteristics were obtained from clinic cards. Results A total of 93 patient was included in the analysis. Adenocarcinoma was found in 53% (n = 49) of the cases and squamous cell carcinoma in 25% (n = 23) of the cases. Overall, lung carcinoma suffers are more likely to be male (69%, n = 64) and smokers (56% n = 52). However, for subtype adenocarcinoma female (OR 2.48 p = 0.048) and non-smokers (OR 7.09, p < 0.001) were more common. 35 patient have their EGFR status available for analysis. It was detected in 57% (n = 20). Non-smokers have an OR of 11.3 (p = 0.0035) for EGFR mutation. Chinese have higher incidence of EGFR mutation compared to other race with OR of 8.25 (p = 0.02). Female has an OR of 3.2, (p = 0.1317). The most common mutation is deletion in Exon 19. Conclusion Adenocarcinoma is now the most common histological subtype of lung carcinoma seen in Kuching population. Incidence of lung carcinoma is higher in smoker than in non-smoker. Our analysis shows that non-smoker and Chinese are significantly more common in patients with EGFR mutation.

Background Amrubicin hydrochloride (AMR) is a key agent for lung cancer. NADPH quinone oxidoreductase 1 (NQO1) metabolizes the quinone structures contained in both amrubicin (AMR) and amrubicinol (AMR-OH). We hypothesized that NQO1 C609T polymorphism may affect AMR-related pharmacokinetics and clinical outcomes. Methods The patients with lung cancer received AMR at a dose of 30 or 40 mg/m 2 /day on day 1-3 at Osaka City University Hospital were enrolled. Plasma sampling was performed at the time points of 24 h after the third AMR injection. The concentrations of AMR and AMR-OH were determined by HPLC method. NQO1 C609T polymorphism was assayed using real-time polymerase chain reaction methods. Results A total of 35 patients were enrolled. The C/C, C/T, and T/T were observed in 12 (34.3%), 16 (45.7%), and 7 (20%) patients, respectively. A dose of 30 mg/m 2 was administered to 19 patients, and 40 mg/m 2 was administered to 16 patients. The mean plasma concentrations of AMR-OH on day 4 at a dose of 30 mg/m 2 and 40 mg/m 2 were 11.02 ± 3.83 and 16.18 ± 6.17 ng/ml, respectively (p = 0.005). In patients with AMR at a dose of 40 mg/m 2 , the plasma concentrations of AMR-OH on day 4 exhibited a tendency toward a relationship with NQO1 genotypes with values of C/C 20.5 ± 5.89, C/T 15.9 ± 5.43, and T/T 11.2 ± 4.47 ng/ml (p = 0.066). The C/C was related to decrease changes in WBC, hemoglobin, and platelet counts (p = 0.01, p = 0.03, and p = 0.0005, respectively). No significant correlations were observed between NQO1 genotypes and clinical outcomes at a dose of 30 mg/m 2 . Conclusions NQO1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities. NQO1 genotype appears to be the candidate biomarker of hematological toxicities of AMR treatment at a dose of 40 mg/m 2 .

Although Non-small cell lung cancer (NSCLC) tumors with activating mutations in the EGFR are highly responsive to EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, development of acquired resistance is almost inevitable. Statins have reported antitumor activity, but it is unknown whether simvastatin can reverse gefitinib resistance in NSCLC with the T790M mutation of EGFR. This study was designed to investigate overcoming gefitinib resistance through a mechanism-based approach using simvastatin. Methods The effects of simvastatin on apoptosis and AKT/β-catenin signaling were examined by annexin V binding assay and immunoblot analysis. We tested the effects of LY294002, siRNA and overexpression for AKT in simvastatin treated gefitinib-resistant NSCLC cells. We also evaluated the role of survivin in simvastatin-induced apoptosis of gefitinib-resistant NSCLC. Results Addition of simvastatin to gefitinib enhanced caspase-dependent apoptosis in NSCLC cells with the T790M mutation. Simvastatin also exerted a inhibitory effect on activation of AKT, leading to suppression of β-catenin activity and expression of its targets, survivin and cyclin D1. Both insulin treatment and AKT overexpression markedly increased p-β-catenin and surivivn level even in the presence of gefitinib and simvastatin. On the other hand, inhibition of AKT by siRNA or LY294002 treatment both caused inhibition of p-β-catenin and survivin. To determine the role of survivin in simvastatininduced apoptosis, we showed that the proportion of apoptotic cells induced by survivin-siRNA and combination of gefitinib and simvastatin was greater than the theoretical addictive effects, whereas survivin up-regulation could confer protection against apoptosis induced by gefitinib and simvastatin. Conclusion Survivin is a key molecule that renders the NSCLC cells with the T790M mutation resistant to apoptosis induced by gefitinib and simvastatin. Taken together, simvastatin may overcome gefitinib resistance in NSCLC with the T790M mutation via AKT/β-catenin signaling dependent down-regulation of survivin and inducing apoptosis.

Lung cancers are among the most common cancers in the world, and the search for effective and safe drugs for the chemoprevention and therapy of lung cancer has become important. In this study, bovine lactoferrin (bLF) was used in both in vitro and in vivo approaches to investigate its activity against lung cancer. A human lung cancer cell line, A549, which expresses a high level of vascular endothelial growth factor (VEGF) under hypoxia, was used as an in vitro system for bLF treatment. A strain of transgenic mice carrying the human VEGF-A165 (hVEGF-A165) gene, which induces pulmonary tumors, was used as an in vivo lung cancer therapy model. We found that bLF significantly decreased proliferation of A549 cells by decreasing the expression of VEGF protein in a dose-dependent manner. Furthermore, oral administration of bLF at 300 mg/kg of body weight 3 times a week for 1.5 mo to the transgenic mice overexpressing hVEGFA165 significantly eliminated expression of hVEGF-A165 and suppressed the formation of tumors. Additionally, treatment with bLF significantly decreased the levels of proinflammatory cytokines, such as tumor necrosis factor-α, and antiinflammatory cytokines, such as IL-4 and IL-10. Levels of IL-6, which is both a proinflammatory and an antiinflammatory cytokine, were also reduced. Treatment with bLF decreased levels of tumor necrosis factor-α, IL-4, IL-6, and IL-10 cytokines, resulting in limited inflammation, which then restricted growth of the lung cancer. Our results revealed that bLF is an inhibitor of angiogenesis and blocks lung cell inflammation; as such, it has considerable potential for therapeutic use in the treatment of lung cancer. Background Signal transducer and activator of transcription 3 (STAT3) activation is frequently found in human lung cancer and is associated with increased metastasis and reduced survival. The molecular mechanisms by which STAT3 enhances cancer invasion have not been well characterized. Methods The expression of microRNAs and target genes was measured by real-time RT-PCR. Protein level was studied by Western blotting. Luciferase reporter assay was used to confirm the direct targeting of microRNAs. Gelatin zymography was used to study matrix metalloproteinase (MMP) activity. Transwell assay was used to investigate cell migration and invasion. Results We find that STAT3 expression is negatively associated with the expression of an endogenous MMP inhibitor, Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) in a set of lung cancer cell lines. Enforced expression of STAT3 decreases the endogenous MMP inhibitor RECK protein but not mRNA level in H460 cells. Conversely, STAT3 inhibitor S3I-201 increases RECK protein in STAT3-activating H1299 cells. We demonstrate that STAT3 up-regulates miR-92a to repress RECK via post-transcriptional inhibition. RECK 3'UTR reporter activity assay suggests RECK is a direct repression target of miR-92a. Delivery of pre-miR-92a reduces RECK protein level while transfection of anti-miR-92a restores STAT3-induced down-regulation of RECK. Anti-miR-92a attenuates MMP activity, migration and invasion of H1299 cells and STAT3-overexpressing H460 cells suggesting miR-92a is critical for STAT3-induced invasiveness. Conclusion we demonstrate that up-regulation of miR-92a by STAT3 is one of the mechanisms by which STAT3 promotes cancer invasion. In addition, we show that RECK is an important mediator of STAT3-induced cell invasiveness. Targeting of the STAT3/miR-92a axis by may be helpful for the treatment of lung cancer.

The CXC chemokine interleukin-8 (IL-8) is an angiogenic growth factor and is overexpressed in various human cancers, including non-small cell lung cancer (NSCLC). We have recently shown that activating KRAS mutations induce IL-8 overexpression, which promotes cell proliferation and migration in NSCLC cells. In the current study, we evaluated clinicopathological and prognostic significances of IL-8 expression in lung adenocarcinomas and its relationship to mutations of KRAS or EGFR. IL-8 mRNA expression was examined by quantitative RT-PCR using 136 surgical specimens obtained from lung adenocarcinoma patients. We then evaluated the association between IL-8 expression, clinicopathological features, KRAS or EGFR mutation status, and survival. IL-8 expression was predominantly expressed in lung adenocarcinomas from elderly patients and those with pleural involvement or vascular invasion. The differential IL-8 expression by age was prominent in nonsmokers but not in smokers. In a nonsmoker subgroup, there was a positive correlation between IL-8 levels and age. IL-8 was predominantly expressed in lung adenocarcinomas with KRAS mutation compared to those with EGFR mutation or wild-type EGFR/KRAS. There was a positive correlation between IL-8 levels and age in a subgroup of KRASmutants or EGFR-mutants. Disease-free survival (DFS) and overall survival (OS) were significantly shorter in lung adenocarcinoma patients with high IL-8 expression than in those with low IL8 expression. Furthermore, lung adenocarcinoma patients with KRAS-mutant/high IL-8 had significantly shorter PFS and OS compared to those with wild-type KRAS/low IL-8. Cox regression analysis revealed that IL-8 expression is an independent prognostic marker in lung adenocarcinomas. Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is an unfavorable prognostic marker in oncogenic KRAS-driven lung adenocarcinomas. Background and Aim of Study Aminopeptidase N (APN) has been reported to play important roles in tumor cell invasion and tumor angiogenesis. It's expression is associated with poor prognosis in patients with colon, pancreatic and lung cancers. The aim of this study is to evaluate antitumor effect of a humanized anti-APN antibody in mouse tumor models. Methods Subcutaneous tumor and tail vein metastasis models were established in immune deficient mice using B16 melanoma cells stably transfected with APN (APN-B16), and H1299 cells highly expressing APN. These tumorbearing mice were intraperitoneally administered a humanized antibody against APN. Sizes of subcutaneous tumor were measured and numbers of tumor nodules on the lung surface were counted. Tumor sections were immunostained with CD31 antibody to assess microvessel density. Results The administration of anti-APN antibody reduced the sizes of subcutaneous tumors and the numbers of lung surface nodules in the mice bearing APN-B16 and H1299. Microvessel density in the tumors was also reduced. Conclusion This humanized anti-APN antibody can suppress growth of tumor highly expressing APN probably through inhibiting angiogenesis.

Background Lymph node metastasis is one of the major factors of the prognosis and is facilitated by lymphangiogenesis, however the precise of the mechanisms is not well understood. In the present study, we investigated the role of COX-2-derived Prostaglandin E2 (PGE2) and Prostaglandin E receptor on formation of pre-metastatic niche that facilitate the lymph node metastasis in Lung Cancer. Methods Lewis lung carcinoma (LLC 3.0 x 105/ml) cell suspensions were orthotopically introduced into the lung parenchyma of wild type mice (WT) and EP3 receptor knock out mice (EP3KO) via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. Results Mediastinal lymph node metastasis formations were significantly suppressed in COX-2 inhibitor (celecoxib, 100 mg/kg/day) treated mice and EP3KO. The expressions of SDF-1, CXCR4, were significantly suppressed in celecoxib treated mice and EP3KO (P < 0.05). CXCR4 antagonist (AMD 3100) decreased lymph node metastasis formation. Furthermore, the accumulation of CD11C+DC was suppressed in COX-2 inhibitor treated mice and EP3KO. In vitro, under EP1-4 agonist stimulation, the SDF-1 concentration in immature DCs was significantly enhanced in EP3 agonist compared to EP1, EP2 and EP4. WT transplanted with EP3KO-BM were significantly suppressed mediastinal lymph node metastasis formation compared to WT transplanted with WT mice. Conclusion These results suggested that pre-metastatic niche formation in mediastinal lymph node was induced by bone marrow derived immature dendritic cells via PGE2-EP3 signaling by induction of CXCR4/SDF-1-axis. Thus, COX-2 inhibitors, CXCR4 antagonists and/or EP3 antagonists may become one of the options to suppress the lymph node metastasis. Methods Expression of nestin and achaete-scute homolog 1 (ASH1) was studied in 21 lung cancer cell lines. To assess the function of nestin, a short hairpin RNA (shRNA) targeting nestin was transfected into two SCLC cell lines (DMS53 and SBC3), and cloned cells that showed apparent down-regulation of nestin were obtained. Nestin expression was also studied immunohistochemically in surgically resected SCLC primary tumors and metastatic SCLC tumors obtained from autopsy cases. Results Nestin was expressed in nine of 10 SCLC cell lines. The nestin expression level was significantly higher in SCLC cell lines than in non-smallcell lung cancer cell lines (P < 0.01). There was a statistically significant positive correlation between the expression levels of nestin and ASH1 in SCLC cell lines. Nestin knock-down cells created by transfection with shRNA exhibited decreased invasion and cell proliferation capabilities. Furthermore, nestin was detected in SCLC tumor cells and tumor vessels in all clinical tumor specimens. Conclusion Nestin is expressed in SCLC in association with neuroendocrine features and participates in malignant phenotypes, including cell growth. Therefore, nestin may be a promising therapeutic target for SCLC. Objective Previous studies reported that the most common chronic condition found among hospitalized patients due to the novel 2009 H1N1 influenza was asthma. However, these studies did not include a concurrent control group. Thus, we investigated the association of asthma status and severity of H1N1 influenza. Methods The study was designed as a multi-site case-control study. Cases were patients who had positive PCR for H1N1 influenza and were admitted to the ICU or general ward with a diagnosis of H1N1 influenza from January 1, 2009 to December 31, 2009. Controls were patients who had positive PCR for H1N1 influenza, but were not admitted to hospitals. Results There were 91 cases, including 41 ICU patients and 50 inpatients, and 56 controls who met the matching criteria were available. Of the 91 cases, the mean age was 47.3 years and 59% were female. Of the 91 cases, 38% had any comorbid conditions. Of the 91 cases, 12 (13%) had asthma. Stratified analysis by comorbid conditions other than asthma showed that among those without any comorbid conditions, 8 of 56 cases (14%) and 2 of 49 controls (4%) had asthma, (OR: 3.92, 95% CI: 0.79-19.42, p = 0.095) whereas, among the 39 subjects with one or more comorbid conditions, one of 7 controls (14%) had asthma and 4 of 35 (11%) cases had asthma (p = 0.83). Conclusions Asthma may be associated with severity of H1N1 influenza among those without any non-asthma comorbid conditions. However, the limited sample size did not allow this study to fully establish a statistically significance. We still recommend asthmatics as a priority group for influenza vaccination and treatment. 

CHI CHING GAN 1 , NORA SAID 1 , WAI MUN WONG 1 , JALEELAHBEEVI MOHD NOOR 1,2 , SHU YI LEE 2 , SALIMAH MAIDIN 2 , TOW KEANG LIM 2 1 National University Hospital, Singapore, 2 National Healthcare Group, Singapore, 3 

This study examines the impact of onsite nurse review and education on postemergency room (ER) outcomes in patients with acute asthma exacerbations. Methods We report a before versus after study of 30 day ER re-admission and outpatient asthma clinic attendance in adult patients discharged from the ER after successful treatment of acute asthma exacerbations. We compared the results in the year before (2010) versus after (2011) the introduction of an onsite asthma education service in the ER. Before discharge from the ER, an asthma nurse educator taught asthma control medication, inhaler technique, and asthma first aid for acute attacks and give an asthma clinic review date. In 2012 we compared the results in 1,323 patients who received face-to-face versus telephonic versus no education. There were no other changes in asthma management protocols in the ER during these 3 years. Results Following the intervention, there was significantly increase rates of both 30-day ER re-admission (4.2% Versus 7.3%, p < 0.01) and outpatient asthma clinic attendance (35.6% Versus 57.4% p < 0.01) in 2010 versus 2011 respectively. In 2012 the ER re-admission rates were 9.1% versus 5.4% versus 2.6% (p < 0.01) and the outpatient asthma clinic attendance rates were 38.9% versus 31.7% versus 17.6% p < 0.05) in patients who received face-to-face versus telephonic versus no education respectively. There were no significant differences in sex, age and ethnic composition. Conclusion (1) Onsite nurse education improves patient safety following discharge from the ER. (2) Onsite nurse education was associated with more ER re-visits for poor asthma control and better asthma clinic attendance. (3) The intensity of asthma education was significantly related to safer patient behavior.

Background and Aim of Study Asthma is a chronic inflammatory disorder of the airways that many cells and cellular elements play a role in pathogenesis. Chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. It causes widespread, variable, and often reversible airflow limitation. Aim of our study is to show frequency and seasonal distribution of out-patient Asthma patients who applied to our Pulmonology Clinic. Method Out-patient records of pulmonary medicine clinic were analyzed and asthma patient records were taken into account. Due to low case numbers in summer time, two summer seasons were included in our study. Asthma cases divided into follow-up and exacerbations groups and both groups' seasonal distribution was analyzed. Results 3288 patients were applied to our clinic in 13 month period. Total 433 (13.2%) patient were diagnosed as asthma and 189 (43.6%) applied as asthma exacerbations and 244 (56.4%) as asthma follow-up. Asthma total case numbers were 101 (23.3%) in spring (March, April, May), 113 (26.2%) in summer (June, July, August), 105 (24.2%) in fall (September, October, November) and 114 (26.3%) in winter (December, January, February). Seasonal Asthma exacerbations' rate were 49 (11.3%) in spring, 36 (8.3%) in summer, 41 (9.5%) in fall and 63 (14.5%) in winter. Conclusion 13.2% of patient had asthma diagnosis. Asthma follow-up rate was close to asthma exacerbations. Family practitioners' active participation in asthma treatment and follow-up might be reason for low case number of follow-up group. Asthma acute exacerbations were lowest in summer, highest in winter and moderate in spring/fall. High Asthma exacerbations' rate in winter might be caused by cold weather conditions, increased infectious disease, allergens and air-pollution. Lowering acute exacerbations of asthma can be achieved by collaborative working between patients, respiratory specialist and also family practitioners.

Objectives Serum eosinophil cationic protein levels in asthma bronchiale patients were compared with healthy controls and the relation between serum eosinophil cationic protein levels, serum total igE levels and serum total eosinophil counts were evaluated. Patients and Methods Serum eosinophil cationic protein(ECP)levels, serum total igE levels, serum total eosinophil counts of a total of 60 patients with asthma (21 of them with asthma and allergic rhinitis) aged 19 to 52 (39 female, 21 male) and 39 (24 female, 15 male) healthy subjects were compared. Results Mean serum ECP levels of 60 patients with asthma bronchiale were significantly higher than the control group (p < 0.05). The level of serum ECP, serum total igE and serum total eosinophil counts of 60 patients were significantly higher than the control group. Serum ECP levels were high both in control group and asthma bronchiale group with significant eosinophilia. Conclusion Asthma bronchiale is a chronic inflammatory airway disease. Eosinophils play a key role in the pathogenesis of asthma bronchiale. The degree of inlammation may be associated with proteins which are derived from eosinophils (such as ECP, etc)In the studies conducted with patients with asthma and allergic rhinitis ECP levels in blood and bronchoalveolar lavage were found to be increased. In some studies it has been suggested that it is more convenient to monitor disease activity with serum ECP levels than eosinophil count. In several studies, the increase in serum ECP levels of patients with asthma and allergic rhinitis is correlated with serum eosinophil counts and serum total igE levels. In our study, in accordance with studies in literature, serum ECP, serum total igE levels and serum total eosinophil counts in patients with asthma were significantly higher than the control group. Introduction Asthma is a chronic condition with significant morbidity, mortality and high economic burden. In Singapore, asthma is a very common problem with prevalence as high as 20% among children, and 5% among the adult Left unchecked, the disease could become an emerging problem of epidemic proportions in both children and adults in the near future. Methods 179 asthmatic child's caregivers who attended high risk asthma clinic at KKH between March to May 2011 who agree to participate in this study were be given a set of questionnaires to be answered. Results 102 mother is the main caregivers, both parent 64, 5 of fathers, 6 others. 84% of caregivers agree counseling and reinforcement by asthma resource nurses are helpful/The reading material(s) is/are given to them is/are beneficial and adequate. 70% of care givers are comfortable in seeing asthma resource nurse for clinical assessment and evaluation at the asthma clinic. 51% of care givers said that they learn best and would like to learn more about asthma care through talking to asthma resource nurses. 74% of care givers used the Written Asthma Action Plan (WAAP) to manage their child mild asthma attack at home.78% of care givers confident in using the WAAP as a guide to manage their child's condition. Conclusion Successful asthma management is a cooperative effort between the patients, their family and all health care professional involves. The asthma resource nurse bridges a gap between the patient and the doctors, to provide comprehensive education and maintain the continuity of care. Backgrounds and Aim of Study Nitric oxide (NO) has been reported as an indicator of asthmatic airway inflammation. Furthermore, distal airway NO (Calv) is useful indicator in distal airway inflammation. NO production has been reported in a variety of resident cells and in inflammatory cells. NO synthase (NOS) exists in three forms: nNOS, eNOS and iNOS. NO production in steroid naive (snBA) is thought to be mainly by iNOS-expressing BECs; however, some reports have pointed out the importance of constitutive NOS in animal models. Here, we investigated correlation with NOS mRNA expression and Calv in distal BECs. Methods Bronchial brushing, BAL and TBLB were performed in BA patients, including snBA and steroid-treated asthma (stBA). BECs were selectively isolated from the distal airway using a sheathed brush. We then examined HE staining and Hansel staining and iNOS expression by immunohistochemistry (IHC). Total RNA was extracted from BECs and BAL cells and iNOS mRNA was measured by qRT-PCR. We then analyzed the correlation of Calv and NOS mRNA expression in BECs. Results Significant inflammatory-cell infiltrations were noted and expression of iNOS protein in the distal airway mainly in BECs and also macrophages and eosinophils. Quantitative RT-PCR showed significantly higher iNOS mRNA expression in BECs than in BAL cells. There are no increases in expression of nNOS and eNOS but is in iNOS in snBA and iNOS showed a significant correlation with Calv. Among the three of NOS, iNOS mRNA expression is highest in distal BECs. Conclusion In the distal airway of asthmatics, BECs are the main NO source and iNOS is thought to be the main enzyme. Results Cough VAS and residual volume improved significantly in all groups, but the degrees of improvement did not differ among the groups. X5 andAX improved and cough sensitivity decreased only in the montelukast group. FeNO fell significantly in the high dose BUD and montelukast groups, the former improved more than the latter. Spirometry, airway responsiveness, and other indices of IOS were unaffected in any group. Coughing tended to relapse more often in the montelukast group during the follow up period. Conclusions In CVA, the effectiveness of montelukast is comparable with inhaled corticosteroids of varying doses at least for a short-term. Background Treatment guidelines for asthma recommend step-down therapy for well-controlled asthma patients. However, the strategy for stepdown therapy has not been well defined. We investigated whether wellcontrolled patients with mild persistent asthma treated by inhaled corticosteroid (ICS) can accept a step-down therapy with reduction in the dose of ICS or leukotriene receptor antagonist (LTRA), pranlukast (PL). Method We recruited 40 adult patients with mild persistent asthma that were well controlled for at least 3 months with a low daily dose (200 μg) of fluticasone propionate (FP) or a therapeutically equivalent dose of budesonide (BUD) or ciclesonide (CIC), and randomly assigned for 6 months with either switching to PL (20 patients in PL group) or inhaled FP 100 μg daily or a therapeutically equivalent dose of BUD or CIC (20 patients in ICS group). During study period, patients were monitored FEV1, Peak Expiratory Flow, respiratory resistance and reactance by forced oscillation technique (FOT), and fractional exhaled nitric oxide (FeNO) for every 2 month. Result During study period, no patients in both treatment groups required hospital admission for an acute exacerbation of asthma and treatment with systemic corticosteroid. The rates of treatment failure were 10% and 35% in the ICS group and the PL group, respectively, and there was no significant difference between both groups. FeNO levels in PL group were significantly increased than ICS group. However, there were no significant differences between both group for the lung function and FOT. Conclusion Patients with mild persistent asthma that is well controlled with the low dose of ICS can be switched to PL safely. However, 35% of PL group failed to maintain well control for 6 months. Further studies are needed to investigate the therapeutic efficacy of LTRA mono therapy on step-down therapy, using protocols specifically tailored to patients with mild persistent asthma. Objective The pathophysiology of cough variant asthma (CVA) is poorly understood. We previously identified a feature of CVAas the heightened cough response to bronchoconstriction. In this study, we investigated whether the measurement of cough sensitivity to methacholine (Mch) may help in the diagnosis for cough variant asthma. Methods The measurements of cough sensitivity to capsaicin (C5), exhaled nitric oxide (ENO), bronchial reversibility to bronchodilator, bronchial responsiveness to Mch (PC20), and cough sensitivity to Mch were performed in patients with chronic non-productive cough (n = 86). Chronic non-productive cough responding to bronchodilator therapy, without wheezes audible on auscultation was diagnosed as CVA. Receiver Operating Curve (ROC) analysis of those measurements for discrimination of CVA from chronic non-productive cough were performed. The measurement of cough sensitivity to Mch was performed as follows. Mch induced bronchoconstriction was detected using partial and full flow-volume curves. We defined a 35% fall in PEF40 (PC35-PEF40) as mild bronchoconstriction. PEF40 was the expiratory flow of partial flow volume curve at 40% above residual volume level. Cough counting was performed during and after inhalation of Mch at PC35-PEF40.

The area under the curve for cough sensitivity to Mch was 0.864 and for C5 was 0.619, ENO was 0.593, bronchial reversibility was 0.539, and PC20 was 0.387. Sensitivity and specificity of cough sensitivity to Mch for discrimination of CVA from chronic non-productive cough were 81.4% and 85.2% respectively. Conclusion The measurement of cough sensitivity to Mch, which is cough counting at mild bronchoconstriction, is useful for discrimination of CVA from chronic non-productive cough.

Background and Aim of Study To determine whether asthma in the elderly have distinct clinical characteristics associated with airflow limitation (AFL), we characterized 80 outpatients with asthma in the elderly by clinical history, pulmonary function tests, impulse oscillometry, and blood analysis. Methods Outpatients aged 65 or older with asthma (n = 80: 40 men and 40 women with a mean ± SD age of 73.11 ± 5.761) were surveyed. AFL was defined as a post-bronchodilator (post-BD) FEV1/FVC < 0.7 in accordance with the Global Initiative for Obstructive Lung Disease. Impulse oscillometry and spirometry were assessed in 53 asthmatics with AFL (75.00 ± 5.704 years, male n = 29) and 27 asthmatics without AFL (69.41 ± 3.775 years, male n = 11) before and after short-acting β2 stimulant treatment. Multiple regression analysis was performed with a forward stepwise approach in variables that were significantly related to AFL in univariate analysis. Results Mean age in the asthma with AFL was significantly higher than the asthma without AFL. Rate of allergic rhinitis (AR) in asthma with AR was significantly lower than the asthma without AFL. Post-BD FEV1% was related to Age, not to AR. Post-BD FVC, post-BD MMF, post-BD V50, and post-BD V25 were related to AFL, but not to age and AR. Post-BD FEV1 was not related to age, AR, and AFL. All post-BD values of impulse oscillometry were not related to AR and AFL. Post-BD Fres was only related to age. Conclusion Post-BD FEV1% in elderly asthmatics was related to age, although post-BD FVC and FEV1 were not related to it. All post-BD values of impulse oscillometry in asthmatics were not related to AFL. Obesity is known as a systemic inflammatory disease, and it is also well known as a risk factor of bronchial asthma. A living body is always affected by internal and external stresses. We have Redox system to protect our living body from these oxidative stresses. Inflammation is closely related to oxidative stress. Obesity is one of the major factors of internal oxidative stress. The aim of the present study was to estimate the relationship between obesity and oxidative stress in bronchial asthma. Patients with bronchial asthma were recruited from the out-patient clinic of our department. We estimated the BMI, blood levels of adipokines (leptine, adiponectine), MDA-LDL, and SOD of the patients. Obesity was the risk factor of hospitalization by asthma attack in female patients in the present study. Obesity patients showed significantly higher level in serum leptine, and significantly lower level in serum adiponectine, compared to not-obesity patients. These differences in serum adipokines were more significant in female subjects. Gender differences were observed about oxidative stress in bronchial asthma in the present study. Those who took systeinyl leukotriene receptor antagonist (LTRA) showed higher serum adiponectine level than those without LTRA therapy. So, LTRA may help adiponectine production to relieve airway oxidative stress of bronchial asthma.

Back Ground Asthma control test (ACT) is used quite frequently as a clinical evaluation of asthma control state. Aim We confirmed the importance of ACT and examined whether question 5(Q5) is necessary as evaluation criteria of ACT in patients with stable asthma. Subjects Eighty-two patients with bronchial asthma whose symptom are stable for more than 3 months (average 48 years old, male:40, female:42, Step1:22,Step2:47,Step3:8,Step4:4). Methods We conducted ACT for subjects and analyzed its points. In addition, we compared with the re-evaluation of 20 points (as total control) excluded Q5. Results There were 56 patients in 25 points (68%), 13 in 24 points (16%), 9 in 23 points and 4 in 22 points more than well control. The one hand, 73 patients got 20 points (89%) and 8 patients were 19 points (10%) in the re-evaluation except for Q5. The ratio of total control (as 20 points) by severity indicated 100% in Step1, 91.5% in Step2, 75% in Step3 and 25% in Step4. Consideration We recommended that criteria of ACT excluding Q5 was more effective than one of current ACT as the clinical evaluation, because total control was about 70% in the evaluation of current ACT however it became higher about 90% in the evaluation of ACT excluding Q5. And the evaluation of ACT trends lower and lower according to severity. IN ASPIRIN  INDUCED ASTHMA   TOMOYUKI MINEZAWA, SUMITO ISOGAI, YOSHIKAZU NIWA,  SAYAKO MORIKAWA, TOMOKO TAKEYAMA, TEPPEI YMAGUCHI,  MARIKO MORISHITA, TAKUYA OKAMURA, SAKURAKO UOZU,  YUKI MIENO, TAMI HOSHINO, MASAMICHI HAYASHI, TORU NAKANISHI Background Although a challenge test using non-steroidal anti-inflammatory drugs (NSAIDs) is crucial for diagnosis of aspirin-induced asthma (AIA), it also has drawbacks in terms of possible side effects. Therefore, alternative in-vitro diagnostic methods for AIA are awaited. Methods Nineteen stable non-AIA patients (9 males and 10 females; mean age, 49.4 years), and 20 AIA patients (9 males and 11 females; mean age, 51.1 years) were enrolled in this study. CD11b and CD16 expressions on the peripheral-blood granulocytes after administration of aspirin and different concentrations of PGE2 in vitro were examined using flowcytometry. Results Aspirin induced a significant increase in CD11b expression on eosinophils (CD16 negative granulocytes) in 19 AIA patients and one non-AIA patient. Increase in CD11b expression on eosinophils by aspirin administration was suppressed by PGE2 in a dose-dependent manner. Conclusions The measurement of CD11b expression on peripheral-blood eosinophils showed very high sensitivity(95.0%) and specificity of (94.7%) in diagnosing AIA. Although this method requires laboratory facilities for flowcytometry, it may be very useful in diagnosis of AIA without side effects. In addition, PGE2 may be involved in regulation of CD11b expression on eosinophils by aspirin administration. Omalizumab is successfully used as supplementary therapy to patients with poorly controlled atopic asthma. Because the majority of commercially available IgE assays measure both free IgE and omalizumab-bound IgE, the total IgE measurement was not available for the therapeutic monitoring. To aim at the therapeutic monitoring for anti-IgE therapy, we newly established an ELISA for free IgE employing a recombinant human soluble FcεRIα as a capture antigen and a biotinylated polyclonal anti-IgE antibody for detection. The assay was technically robust with a lowest limit of detection of 18.75 ≠g/mL. The spkike-recovery rate in serum was determined between 91.1% and 98.5%. Using newly established an ELISA, we measured the serum free IgE levels in five patients every week after first injection of omalizumab. Omalizumab significantly reduced serum free IgE levels prior to the second omalizumab injection in all patients. We also measured the serum free IgE levels in 8 patients treated with omalizumab over 12 months. It is believed that benefit of omalizumab treatment in severe asthma needs to keep serum free IgE concentrations below 50 ≠g/ml. In 3 of 8 patients with long-term use of omalizumab, the serum free IgE concentrations were higher than 50 ≠g/ml. The free IgE ELISA allows us to easily quantify free IgE and thus to monitor patients treated with Omalizumab. Our data suggest that the reevaluation of injection doses would be required in long-term use of omalizumab. MASAMITSU TATEWAKI, HIROKUNI HIRATA, MINEAKI WATANABE,  NARUO YOSHIDA, TATSUYA YOKOYAMA, TAKUYA Background Inflammatory cytokines and chemokines have been reported to play important roles in the pathogenesis of bronchial asthma. However, no criteria for the classification of 'smoker' and 'atopic' in bronchial asthma have been defined. In this study, we compared the levels of several cytokines found in the bronchoalveolar lavage (BAL) fluid of patients classified as having bronchial asthma. Methods Cell subpopulations in BAL fluid were counted. BAL fluid levels of in IL-4, -5, -13, -17, and -33 and regulated and normal T cell expressed and secreted (RANTES) were measured using a bead suspension array in 36 asthma patients (13 males, 23 females; mean age, 39.53 years) who had never smoked, 18 asthma patients (11 males, 7 females; mean age, 30.67 years) who were ex or current smokers (Brinkman index (BI): 1-399), and 10 asthma patients (9 males, 1 female; mean age, 50.2 years) who were current heavy smokers (BI: above 400). Relationships were assessed by Spearman's rank correlation analysis. Results The number of lymphocytes in BAL cell subpopulations of never smokers were significantly higher than those of heavy smokers. The number of neutrophils was significantly higher in heavy smokers than in never smokers. Levels of IL-33 and RANTES were significantly higher in never smokers than in heavy smokers. In addition, the levels of IL-33 and RANTES in never smokers were significantly higher in atopic asthma patients than in non-atopic asthma patients. A good correlation was noted between RANTES and lymphocytes or IL-33 in atopic asthma patients who were never smokers. Conclusions Differences in the cell types of BAL fluid, as well as in the levels of IL-33 and RANTES in asthma patients with or without smoking, might reflect pathogenesis. Background and Aim of Study FF/VI is a combination inhaled corticosteroid/long-acting beta2 agonist in development as a once-daily asthma therapy. This analysis evaluated ethnic sensitivity of FF/VI or FF alone in asthma patients in Japan and Korea. Methods A pooled analysis of randomised, double-blind, multicentre phase IIb/IIIa trials. Efficacy data from three studies were compared between patients from Japan (n = 148) and 'Not-Japan' countries (n = 3066). Change from baseline in trough FEV1 after 12 weeks with FF/VI 100/25 mcg, FF 100 mcg or placebo was analysed from two studies using an ANCOVA model, with terms for baseline FEV1, region, gender, age, treatment group, study and region by treatment interaction. FF/VI 200/25 mcg and FF 200 mcg data were from one study. Safety data from six studies were compared between patients from Japan/Korea (n = 194) and Not-Japan/Korea (n = 4037). Pharmacokinetic and pharmacodynamic data were collected. Background Allergic sensitization is important step in the pathogenesis of asthma. However, little is known about which molecules are critical regulators for establishing allergic sensitization through the airway. Thus we investigated the global gene expression analysis to identify candidate genes and signaling pathways involved in the house dust mite extract (HDM) -induced allergic airway sensitization in mice. Methods We sensitized and challenged mice with HDM or saline as control through the airway on day1, 8, 15. On day18, HDM-sensitized and challenged mice got asthma-like responses, including eosinophilic airway inflammation and airway hyperresponsiveness. On day 0 (the day before first sensitization), day7 (the day before second sensitization) and day14 (the day before challenge), we extracted total RNA from lung tissues. Then we performed mRNA microarray analysis. Data analysis was performed using GeneSpring and Ingenuity Pathways Analysis. Results Repeated HDM instillation into airway induced stepwise up-regulation of myeloid differentiation-2 (MD-2), the lipopolysaccharidebinding component of the Toll-like receptor 4 signaling complex. Conclusions Our data suggest that innate immune-related gene including MD-2 might regulate to establish allergic airway sensitization to HDM in mice. Background MicroRNAs (miRNAs) have been reported as useful therapeutic and diagnostic targets for patients with asthma. Exosomal miRNAs in serum are stable so that this might be useful as biomarkers. However, little is known regarding which exosomal miRNAs in the serum are suitable for the real-time monitoring of allergic inflammation in the airway. We, therefore, investigated the miRNA microarray analysis to identify candidate exosomal miRNAs in the serum involved in the allergic inflammation in the airway of mice. Methods We sensitized and challenged mice with house dust mite extract (HDM) or saline as control on day1, 8 and 15. On day 18, we collected lung tissues and serum, and extracted total RNA from lung tissues and exosomes in the serum. Then we performed miRNA microarray analysis using these extracted RNA. Data analysis was performed using GeneSpring software. Gene network analysis was performed using Ingenuity Pathways Analysis. Results We identified same HDM-inducible miRNAs both in the lung and exosomes in the serum. Conclusions Our data suggest that exosomal miRNAs in the serum we identified might be new diagnostic biomarker or therapeutic targets for allergic inflammation in the airway. YASUHIRO GON, SHUICHIRO MARUOKA, YOSHITAKA SHINTANI,  DAISUKE KOYAMA, TADATAKA SEKIYAMA, HISATO HIRANUMA,  TOSHIO INOUE, IKUKO TAKESHITA, Exosomes are cellular secretory vesicles containing microRNAs (miRNAs). Secreted exosomes are able to transfer miRNAs into the recipient cells, and consequently transferred microRNA potentially modulate the function of the cells. We hypothesized that airway secreted exosome derived miRNA profile in allergic airway inflammation might differ from that of normal condition. We studied exosomal miRNA profile of the mice with house dust mite (HDM)induced allergic airway inflammation. The exosomes were obtained from bronchial alveolar lavage fluid (BALF) from the mice 2 days after the last allergen exposure. The number of purified exosomes was increased 8.9 times in the HDM-exposed mice compared to the sham mice. The exosomal miRNAs in the BALF were analyzed by a miRNA array (1966 microRNAs probes). The profiles of exosomal miRNAs in the HDM exposed mice were significantly different from that of the sham mice. Interestingly, over 90% of the increased exosomal miRNAs after HDM exposure (2-fold or more, p < 0.05), decreased inversely in the lung tissues with allergic inflammation. In contrast, over 80% of the decreased exosomal miRNAs after HDM exposure (0.5-fold or less, p < 0.05), increased inversely in the lung tissues. Our observations suggest a possibility that exosomal miRNAs are selectively secreted to the airway fluid in allergic inflammatory condition. The regulation of cellular transcriptome by selective secretion of exosomal miRNAs might be involved in the pathogenesis of allergic inflammation in the airway. Because eosinophils specifically accumulate to the sites of Th2-type inflammation, we hypothesized that UA acts as an activator for eosinophils. Methods Eosinophils isolated from peripheral blood of normal individuals were incubated in the presence or absence of monosodium urate (MSU), an uric acid crystal, and then release of ATP and cytokines were evaluated. Results Eosinophils exposed to MSU crystals rapidly (i.e., within 1 min of exposure) released ATP into the extracellular milieu. Eosinophils incubated with MSU crystals, but not those incubated with uric acid solution, produced IL-6 and IL-8/CXCL8. Other cytokines and chemokines were also produced by eosinophils incubated with MSU crystals. Conclusions UA stimulated eosinophils to release ATP and product cytokine(s). Thus, human eosinophils may respond to particulate damageassociated endogenous danger signals. These responses by eosinophils to tissue damage may explain the self-perpetuating nature of chronic inflammation in certain human diseases, such as asthma.

Background and Aim of Study Pirfenidone, an antifibrotic drug with antiinflammatory and antioxidant effects, delays fibrosis in idiopathic pulmonary fibrosis (IPF). Patients with IPF have a greater cough reflex sensitivity to inhaled capsaicin than healthy people, and cough is an independent predictor of IPF disease progression; however, the effects of pirfenidone on cough reflex sensitivity are unknown. Methods After challenge with an aerosolized antigen in actively sensitized guinea pigs, pirfenidone was administered intraperitoneally, and the cough reflex sensitivity was measured at 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed, and the tracheal tissue was collected. Results Pirfenidone suppressed the capsaicin-induced increase in cough reflex sensitivity in a dose-dependent manner. Additionally, increased levels of prostaglandin E2, substance P, and leukotriene B4, but not histamine, in the BAL fluid were dose dependently suppressed by pirfenidone. The decrease in neutral endopeptidase activity in the tracheal tissue was also alleviated by pirfenidone treatment. The total number of cells and components in the BAL fluid was not influenced. Conclusion These results suggest that pirfenidone ameliorates isolated cough based on increased cough reflex sensitivity associated with allergic airway diseases, and potentially relieve chronic cough in IPF patients who often have increased cough reflex sensitivity. Prospective studies on cough-relieving effects of pirfenidone in patients with IPF are therefore warranted. Background and Aim of Study It is well known that women suffer from severe asthma more frequently than men. Interleukin (IL)-23-IL-17-producing CD4+T cell (Th17 cell) axis may play an important role in the development of chronic inflammatory diseases including asthma. The aim of this study is to investigate whether differences in asthma severity between sexes are associated with the production of IL-23/IL-17 in an experimental model of allergic asthma. Methods Eosinophil counts and cytokine profiles in bronchoalveolar lavage (BAL) fluids were assessed in ovalbumin (OVA)-sensitized and challenged male and female IL-23-deficient mice and wild-type C57BL/6 mice. Results Aerosolized OVA challenge caused marked eosinophilia in BAL fluids. The numbers of eosinophils in BAL fluids were significantly higher in male IL-23-deficient mice than in male WT mice. On the other hand, there was no significant difference in the numbers of eosinophils in BAL fluids between female IL-23-deficient mice and female WT mice. The levels of IL-17 in BAL fluids tended to be lower in male IL-23-deficient mice than in male WT mice while there was no significant difference in the levels of IL-17 between female IL-23-deficent mice and female WT mice. Conclusion The difference in severity of eosinophilic airway inflammation between sexes may be associated with the different production of IL-23.

We experienced two cases of femoral neck fracture in extremely elderly patients who developed pulmonary complications, right-side pleuritis in one and bilateral aspiration pneumonia in the other. The first case was a 94-year old woman. Her case of left femoral neck fracture was complicated with right-side recurrent pleuritis. We performed several pleural punctures and administered antibiotics. The pleuritis was partly due to parapneumonic effusion. Surgery for the fracture was subsequently performed. Pleural effusion did not recur, and the patient was discharged. The second case was a 92-year old man whose right femoral fracture was complicated with aspiration pneumonia in the bilateral lungs. The family did not wish to do the operation because of the patient's extreme age. We performed IVH and the administration of antibiotics of TAZ/PIPC or PIPC conservatively. The patient improved gradually, and oral feeding became possible. The rehabilitation of his legs gradually increased his ADL according to the spontaneous healing of the femoral neck fracture. Since a supine position was required after the femoral fracture, protection against decubitus and skin care was also needed. In any case, when treating the very elderly for femoral fractures in the early stages, pulmonary complications (pneumonia, etc.) might be prevented as reported also by several other references.

Background Nursing and healthcare-associated pneumonia (NHCAP) is common in elderly patients and is also associated with aspiration and drug resistance to antibiotics. Moxifloxacin (MFLX) is a respiratory quinolone effective to anaerobes. Additionally, it is unnecessary to reduce the amount of MFLX even in patients with renal dysfunction. Therefore, we assessed the efficacy and safety of MFLX in patients with NHCAP. Patients and Methods NHCAP patients with mild and moderate severity by A-DROP system of JRS community-acquired pneumonia guideline visited our hospitals from September 2010 to March 2012. Clinical symptoms, chest X-rays and/or CT, peripheral white and red blood cell and platelet counts, serum CRP, AST, ALT, BUN, creatinine were evaluated. Clinical efficacy of MFLX was categorized into effective, ineffective and undeterminable. Patients aged over 65 years old were considered aged patients. All side effects were also evaluated during MFLX treatment. Collectable sputum samples were also bacteriologically evaluated. Results Forty patients were evaluated, and average age was 74.1 yeas old, male/female were 19/20, 92.5%(37/40) of them had one or more comorbidities. Median duration of administration was 7 days (3-15 days). The efficacy in all patients was 87.5% (35/40). The efficacies in each age group were 87.9% (aged over 65 years old), 87.5% (aged under 64 years old), and in each pneumonia severity group by the A-DROP system were 91.2% (mild), 85.7% (moderate). Diarrhea was observed in one patient (2.5%) after starting MFLX administration. Sputum samples were investigable in 20 patients, and Grampositive cocci in 15 samples, Gram-negative rods in 16 samples and Candida in one sample were detected. In these samples, 9 samples showed S. aureus (1), S. pneumoniae (2), alpha-Streptococcus (1), K. pneumoniae (1), H. influenzae (1), M. catarrhalis (2), P. aeruginosa (1). Conclusion MFLX is effective and safe in patients with NHCAP.

A 76-year-old female was diagnosed as systemic sclerosis and collagen vascular diseases associated interstitial pneumonia and administration of prednisolone (10 mg/day) and mizoribine (150 mg/day) was initiated since 2009. Cavitary mass lesion was recognized in the right lower lobe of lung in August 2011, and it became larger in its size. She was undergone bronchoscopy for further examination. The culture of bronchial washing fluid of the cavitary lesion resulted in positive for Mycobacterium avium, M. intracellulare, Aspergillus fumigatus, and A. terreus. At that time, the culture result of Aspergillus spp. was considered as colonization, she was diagnosed with pulmonary nontuberculosis mycobacteriosis, and administered clarithromycin 800 mg/day, rifampicin 450 mg/day and ethambutol 750 mg/day. In February 2012, she developed the right hydropneumothorax. The microbial examination revealed Gaffky number 8 on right pleural effusion and M. avium was cultured. The right pneumothorax and empyema was refractory to the drainage therapy, the patient received right lower lobectomy. Five months after surgery, the infiltration of right middle lobe gradually deteriorated and developed the fistula. The dead space of right thorax and pleural effusion were also increased. A. fumigatus was isolated from right pleural effusion and the patient was diagnosed with Aspergillus empyema. Intravenous micafungin (MCFG) was started. However, the disease state was unresponsive to conservative medical management, we performed the open window thoracostomy and the debridement of the focus in the parietal pleura. Additionally, local antifungal treatment with daily dressing with amphotericin B immersed gauze was started in combination with systemic MCFG administration. Antifungal treatments were continued over 3 months and the patient gradually improved. Although Aspergillus empyema is a rare and life-threatening infectious disease, the standard therapeutic strategy does not exist. We report an Aspergillus empyema case successfully treated with open window thoracostomy and systemic and local anti-microbial administrationand review the literatures.

Background and Aim of Study Human metapneumovirus (hMPV) was discovered in 2001 as a member of the Paramyxoviridae family and accumulating data shows that hMPV is one of the most common causative agents in human respiratory tract infection. Although a lot of studies have revealed the clinical characteristics of hMPV infection in children, there are few reports focusing on that in adults. An outbreak of hMPV infection occurred at a long-term care facility for mentally handicapped patients in Okinawa, located in a subtropical region of Japan. We evaluated the clinical and radiological findings in patients with hMPV infection. Methods RNA was extracted from nasopharyngeal swabs using a DNA/RNA elution kit and analyzed with a multiplex PCR kit (Seeplex RV15 OneStep ACE Detection, Seegene Inc, Seoul). We retrospectively evaluated the medical and nursing records of all patients in the facility during the outbreak period. The chest X-rays and CT scans were analyzed by three physicians specialized in pulmonary diseases. Results The outbreak occurred from March 28 to April 30 in 2012 and 63 patients had symptoms such as fever, running nose, sore throat and cough. hMPV-RNA was detected in 11 out of 14 patients. Out of 63 symptomatic patients in total, 24 (38%) had pneumonia on the chest X-ray. Bilateral shadows spread radially from the bilateral hili with bronchial wall thickening was observed in most patients with pneumonia. CT scans were performed in 5 patients and segmental distributions of parenchymal abnormalities were commonly observed. Bacterial co-infection was detected in 6 patients and Streptococcus pneumoniae was isolated from 4 patients. Compared with patients without pneumonia, patients with pneumonia were older and had more abnormalities in the laboratory examination. Conclusion hMPV caused pneumonia at a high rate and a bilateral bronchopneumonia pattern was a characteristic finding.

Background and Aim of Study Respiratory system was constantly attacked by multiple infectious agents. These attacks lead to infections of nose, paranasal sinuses, ear, pharynx and nasopharynx which are called upper respiratory tract infections (URTI). If coughing is prominent symptom, some of the patients with URTI apply to Pulmonary Medicine outpatient clinic. The aim of our study is to express out-patient URTI rate in our Pulmonary Medicine clinic. Method Out-patient records of pulmonary medicine clinic were analyzed and URTI patient records were taken into account. Due to low case numbers in summer time, two summer seasons were included in our study. Results 3288 patients were admitted to our clinic in 13 month period. Total 539 (16.4%) patient were diagnosed as URTI. URTI case numbers were 112 (20.8%) in spring (March, April, May), 102 (18.9%) in summer (June, July, August), 114 (21.2%) in fall (September, October, November) and 211 (39.1%) in winter (December, January, February). Discussion 16.4% of the patients who admitted to our department were diagnosed with upper respiratory tract infections, and treatment was given. Because of the coughing which is the major symptom of respiratory diseases, the patients with URTI apply to Pulmonary Medicine outpatient clinic. Some of the patients with URTI who have not only coughing but also sore throat, postnasal drip and nasal congestion apply to Pulmonary Medicine clinic instead of ENT clinic. Reason of this might be patient's fear of the lower respiratory tract infections and pneumonia risk.

The Gram-positive pathogen Streptococcus pneumonia(Spn) has been intensely studied for almost over a hundred years, more and more studies found that autophagy is a protective mechanism for human lung epithelial cells in the infection of Spn. This study was designed to investigate the expression of Microtubule-associated protein light chain 3(LC3) in human alveolar epithelial cells A549 and the effect of Streptococcus pneumoniae and 3-Methyladenine (3 MA) on it, lay the foundation for studying on the role of autophagosome in the process of Streptococcus pneumoniae infection. Methods Human pulmonary epithelial cells cultured in vitro and stimulated with Streptococcus pneumonia. Extract the Ribonucleic acid (RNA) of A549 cells on 12 hours and detect LC3 mRNA expression by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The necrosis cells of control group, 3-MA group, Spn group and Spn added with 3-MA group were detected by the necrosis kit after 12 hours by Non-Radioactive cytotoxicity assay respectively. Results The expression of LC3 mRNA stimulated of 3 MA deteced by RT-PCR was different. The necrosis test showed the blank group and 3-MA group was not significantly different, Spn group and Spn added with 3-MA group significantly different. The expression of LC3 mRNA in alveolar epithelial cells stimulated with Streptococcus pneumoniae was significantly different. The necrosis number of alveolar epithelial cells which added 3 MA was increased. Conclusion Our results indicate that autophagy signaling pathway prevents apoptosis in type II alveolar epithelial cells infected with Streptococcus pneumoniae and may represent a molecular target for promoting cell survival during infection by respiratory pathogens.

Background Bronchial carcinoma currently ranks as the leading cause of cancer related deaths in men and women. At the time they are diagnosed, the majority of lung cancers have progressed to an advanced state. So early diagnosis is essential. Fibre optic bronchoscopy (FOB) exerts its role in this regard.

This observational study was carried out in the NIDCH, Mohakhali, Dhaka, Bangladesh from January to December, 2012. In this period, total 1190 Patients underwent FOB after fulfilling inclusion and exclusion criteria. Biopsy, brush and bronchoalveolar lavage (BAL) were obtained from suspected cases to confirm bronchial carcinoma. Results 1190 patients were included in this study with a male-female ratio 9:1. More than 76% patients aged 40 years and above. Mitotic lesion was detected in 243 cases (20%). Inflammatory lesion was detected in 70% cases and remaining patients had normal or some other rare findings. Histopathology of bronchial biopsy from the mitotic lesion of 188 cases revealed that 68 patients (36%) had squamous cell carcinoma and 24 patients (13%) had adenocarcinoma. Histopathology of bronchial brushing revealed that 37 patients (12%) had squamous cell carcinoma and 76 patients (25%) had adenocarcinoma. Conclusion Bronchoscopy is the most useful investigation in bronchial carcinoma. It can provide histological confirmation, the extent of the disease, evidence of inoperability and endobronchial site of the tumour. But newer technique like endobronchial ultrasound (EBUS), transbronchial needle aspiration (TBNA), simultaneous autofluorescence endoscopy (SAFE) should be introduced to increase further diagnostic yield, which already we have started in Bangladesh. Technical development in last two decades has made it possible for pulmonologists to do endobronchial ultrasound (EBUS). With EBUS miniprobe, the multilayered structure of the tracheobronchial wall can be analyzed better than any other imaging modality. Instead of fluoroscopic guided biopsy, EBUS can be used to biopsy peripheral lesions. EBUS-transbronchial needle aspiration has proved valuable for sub-carinal hilar and mediastinal lymph nodes. In National Institute of Diseases of the Chest and Hospital (NIDCH), Dhaka we have introduced EBUS for the first time in Bangladesh. So far, we have done EBUS in 107 patients and our result is as follows: Adenocarcinoma 32 (30%), Squamous cell carcinoma 27 (25%), Small cell carcinoma 9 (8%), Tuberculosis 22 (21%), Lymphoma 2 (2%), inconclusive, 15 (14%). This is very much conclusive in comparison with conventional modalities of diagnostic procedure which we used to do previously (e.g. conventional bropnchoscopy, CT-guided FNAC, etc.). Studies have shown that EBUS is cost-effective as it reduces the need for more morbid and costly invasive procedure like mediastinoscopy or thoracotomy. Prospective studies are needed in Bangladesh to see how EBUS will help in populations having lymphadenopathy in Chest X-ray, where other procedure does not give conclusive diagnosis. Background Self-expanding metal stents have been used successfully to overcome large airway obstruction due to malignant pulmonary disease. The technique has been modified to place stents under direct vision using the fibreoptic bronchoscope. The effect of this procedure on lung function and patient well being was investigated in three patients in NIDCH, Dhaka, Bangladesh. Stent insertion was uncomplicated. Methods Three patients with malignant tracheobronchial tumours were treated for symptoms of life threatening airways obstruction or collapse of a lung by the insertion of an expandable metal stent(s) under local anaesthetic using a fibreoptic bronchoscope. All had inoperable cancer and histopathological diagnosis was conclusive. All patients had the stents inserted at one sitting and one patient needed the debulking of the tumour. Measurements were performed in all the patients before and after stenting and included objective measures (pulmonary function tests, arterial blood gas tensions) and non-objective measures (patient well being, performance status). Results Overall, 100% of patients showed symptomatic improvement. Patients in whom measurements were performed all the patients showed improvement in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR) and arterial oxygen tension (PaO2). There were no perioperative complications. Conclusions In suitable patients with either extraluminal or intraluminal tumour, or both, the insertion of expandable metal stents using a fibreoptic bronchoscope and local anaesthetic is a valuable addition to other palliative therapies in the treatment of lung cancer.

Background Topical anesthetics can affect the procedures for implementing fiber-optic bronchoscopy (FOB). Some way can be done under local anesthesia. This study compare spray and nebul topical anesthetic in patients undergoing FOB. Methods This study was conducted at Adam Malik Hospital involving 64 patients, 55 (85.9%) men, aged between 22 to 75 years will be done bronchoscopy. Randomly, each sample will be spray with 10% lignocaine 5-7 sprayer (n = 32) or nebulized 5 mL of 2% lidocaine (n = 32). In addition, each patient will receive 2% lignocaine through the bronchoscope into the airway during procedure under direction operator. All patients received diazepam 5 mg intramuscularly for premedication 3 hours before procedure. The amount of coughing during procedure are recorded and after procedure patients were asked to indicate the sense of discomfort in Visual Analoque Scale. Results The procedure was performed during bronchoscopy are 100% washing and 25% brushing in spray group, and 100% washing and 31.3% brushing in nebuls group. Lignocaine dose used in both groups there is a significant difference (p = 0.002) where the average lignocaine on spray group and nebulized group are 204.38 mg and 170.94 mg respectively with 41.05 mg SD. Number of cough in the two groups was not significant (p = 0.469) where the average cough in spray group 1 (0-10) times and nebulized group 2 (0-9) times. Average VAS score in spray group 1.60 cm and 1.65 cm in nebulized group. VAS score in the two groups did not different significantly (p = 0288). Statistical result on the number of coughs and VAS score in both groups showed no differences in discomfort with p value 0.410 and 0.378. Conclusion The effect of spray and nebulized topical anesthetic are equally to reduce patient discomfort undergoing FOB. Keyword FOB, spray, nebuls, VAS.

AYAKO IGARASHI 1 , YASUTAKA KAWAI 1 , MITSURU OGRI 1 , TAKUYA SASAKI 2 , RYO OTA 2 1 Department of Respiratory Medicine, Oji General Hospital, Tomakomai, Hokkaido, Japan, 2 Department of otorhinolaryngology, Oji General Hospital, Tomakomai, Hokkaido, Japan A foreign body of the hair crab's shell in the airway is very rare. Management of this type of foreign body is difficult and even thoracotomy might be considered. We experienced a case of a foreign body of the hair crab's shell in the bronchus retrieved through the tracheostomy. The patient was a 64-year-old man who aspirated a piece of hair crab shell accidentally when sucking the leg meat. Mild cough and throat discomfort developed immediately. He presented to our hospital the next day complaining of dyspnea in the supine position that had continued overnight. Physical examination showed inspiratory stridor of the left lung. Although the chest X-ray was normal, the chest CT scan revealed a foreign body of the hair crab's shell in the left main bronchus, which was confirmed by flexible bronchoscopy. Initially we tried to grasp the shell with alligator forceps but failed due to its slippery surface. It was only moved slightly centrally with a retrieval net and basket forceps. Therefore he underwent tracheostomy under general anesthesia to facilitate the following procedure. Since the spines on the shell had penetrated the bronchial mucosa, it was impossible to retrieve the shell using a rigid bronchoscope and forceps. Finally it was removed through the tracheostomy by nasal forceps and the rigid endoscope for endoscopic sinus surgery.

Usefulness and safety of endobronchial ultrasoundguided transbronchial needle aspiration (EBUS-TBNA) have been established recently, but no study has evaluated whether or not aging increases the risk of the procedure. In the present study, we aimed to assess the usefulness and safety of EBUS-TBNA in older patients.

The medical records and database of 109 patients who received EBUS-TBNA between 2008 and 2011 at Nagoya University Hospital, Nagoya, Japan were reviewed retrospectively. All patients underwent bronchoscopy under light sedation with midazolam. A total of 34 patients were aged 70 years or older (the older group) and 75 were aged 69 years or younger (the younger group). We analyzed patients' characteristics, changes of clinical parameters, usable doses of midazolam and lidocaine, procedure duration, geographic data of biopsied lymph nodes, diagnostic yield, and complications in both groups. Results There were more commodities in the older group. Four patients (11.8%) in the older group had poor performance status (2) (3) . Systolic blood pressure at baseline was significantly higher in the older group. There were no statistical differences between the two groups in some clinical parameters (minimum oxygen saturation [SpO2], reduction in SpO2, maximum oxygen supplementation, elevation of systolic blood pressure, increase in heart rate) during the procedure. Diagnostic performance in older patients was similar to that found in younger patients. There was no difference in the frequency of complications between both groups. Conclusion Safety and usefulness of EBUS-TBNA in older patients were comparable with those in younger patients.

Complicated parapneumonic effusions are common. Yet, their optimal management continues to be a matter of debate. Medical thoracoscopy has been playing an increasing role in the management of complicated pleural infections but its utility remained controversial. Here, we report two cases of complicated parapneumonic effusions, in which medical thoracoscopy may have found its niche. The first patient was a 32 year old male admitted to cardiology with the diagnosis of tricuspid valve infective endocarditis with tricuspid regurgitation. This was complicated by septic emboli to the lungs, spleen, right iliacus and right obturator externus muscle. On day 30 of admission, he developed a large right complicated parapneumonic pleural effusion for which initial chest tube drainage was unsuccessful. After a multidisciplinary consult with the cardiothoracic surgeon, the patient was referred to the pulmonologist for a trial of intrapleural fibrinolysis first, as his operative risk was deemed significant. He underwent medical thoracoscopy as well as intrapleural fibrinolysis. A repeat chest radiograph (CXR) on day 5 of fibrinolysis showed dramatic improvement. The second patient was a 49 year old male, premorbidly wheelchair bound, with multiple comorbidities who was admitted with a left complicated parapneumonic effusion. Two consecutive chest tubes inserted yielded poor drainage. Decision was made to proceed with medical thoracoscopy as he was deemed a high risk surgical candidate. Multiple locules and dense adhesions were noted during the procedure. These were broken down to achieve drainage and a new chest drain was inserted. A repeat CXR one month later demonstrated complete resolution of the left pleural effusion. Hence, before the jury is out with regards to the optimal management of complicated parapneumonic effusions, a multidisciplinary approach would be appropriate and we strongly believe that medical thoracoscopy has a role in the carefully selected patient. Background Transthoracic needle biopsy is one of diagnostic procedure of peripheral lung lesion and pleural lesion. However the performance and complication of procedure is varied depend on lesion characteristic and operator skill.

Retrospective study of patients with peripheral lung lesions underwent CT guide transthoracic biopsy. Biopsy procedure was performed using 18 gauge co-axial needle cutting biopsy under spiral scan technique with 1.0 mm collimation in department of Radiology SDMC medical center in 2012. Results Total 46 patients who were eligible for biopsy was performed by single experienced intervention radiologist. Female were 63.6% of cases. Mean age of patient was 64.4 years. Most common chest radiographic finding was intra-pulmonary mass lesion. The locations of lung lesions were RUL (22.7%), RML (22.7%), RLL (15.9%), LUL (22.7%), and LLL (13.6%). Two cases were extra-pulmonary pleural lesions and one having multiple pulmonary nodules. The results of biopsy were adenocarcinoma (47.7%) of all biopsy procedures which most of those having lesion size more than 3 cm diameter. The remaining diagnostic results were tuberculosis (9.0%), squamous cell carcinoma (4.5%), small cell carcinoma (2.2%), poorly differentiated carcinoma (2.2%), mesothelioma (2.2%), chronic fungal infection (2.2%) and silicotic nodule (2.2%). Other non diagnostic pathological finding was chronic interstitial pneumonitis with fibrosis (13.6%). Inadequate samples were noted in 2 cases having less than 2 cm size lesion. Pneumothorax was commonly observed procedure related complication was 68% of all biopsies and 93% having mild degree of pleural air observed from imaging and did not require drainage or chest tube thoracostomy. Among patients developed pneumothorax 50 % having lesion less than 3 cm diameter. Conclusion Co-axial needle thoracic biopsy provides acceptable diagnostic performance for peripheral lesion which mostly are malignancy. In addition, minimal pneumothorax is commonly observed after procedure. Pulmonary Rehabilitation is an essential component in the management of obstructive lung disease. The recommended minimum length of a program is six weeks. However, the program in our institution has been shortened to four weeks due to logistic and practical purposes. This study aims to determine if the program provided benefit to its participants with regard to functional capacity, exercise tolerance and quality of life (QOL). Data from 19 participants, 6 with chronic obstructive lung disease and 13 with bronchial asthma were analyzed. The FEV1, 6 minute walk test and chronic respiratory questionnaire were used to measure the participants' functional capacity, exercise tolerance and QOL. These parameters were measured before starting and upon the completion of the program. Participants with COPD had an average age of 59.67 years, 5 were male and 1 female. Upon completion of the 4 week program, half had an improvement on functional capacity, two thirds had improved exercise tolerance, while five out of six felt improvement of QOL. Participants with bronchial asthma had an average age of 58.24 years, 6 were male and 7 were female. Less than half (46%) had improved exercise capacity, three-fourths were noted to have increased exercise tolerance while eight out of five (62%) showed improvement of QOL after the 4 week program. The 4 week pulmonary rehabilitation program of our institution showed modest improvement in the functional capacity, exercise tolerance and QOL of the participants. It is still to be determined if the shortened duration of the program provides significant improvement as more data are needed. Background Expiratory muscle activity during reverse sniff, a maneuver akin to "blowing your nose", increases with stepwise increments in reverse sniff nasal expiratory pressure (RSNEP), and this maneuver is useful for assessment of expiratory muscle strength (ERJ P3519, 2012). In patients with neuromuscular diseases, RSNEP may be influenced not only by expiratory but also upper airway muscle activity. In fact, upper airway muscle significantly contributed to sniff nasal inspiratory pressure, a reliable maneuver for measurement of inspiratory muscle strength (ERJ P913, 2008). How do expiratory and upper airway muscles behave during reverse sniff at sitting and supine positions? Methods In 7 healthy subjects, age 25.4 ± 4.4 years, we inserted fine wire electrodes into genioglossus (GG) and transversus abdominis (TA) muscles using high-resolution ultrasonography. RSNEP was measured through a catheter that occluded one nostril, while contralateral nostril remained open. Subjects performed short, sharp, maximum and variable intensity of reverse sniff, beginning from FRC at sitting and supine positions. GG and TA EMG activities were expressed as percent of maximum EMG (%EMGmax). Results Mean RSNEP at sitting and supine positions were 74.7 ± 25.5 and 76.0 ± 30.2 cmH2O, respectively. In all subjects, both GG and TA EMG activities increased with stepwise increments in RSNEP at sitting and supine positions. There were significant linear relationships between RSNEP and EMG activity of each muscle (GG: sitting r = 0.66-0.89, supine r = 0.71-0.94, TA: sitting r = 0.77-0.92, supine r = 0.66-0.96). %EMGmax/RSNEP (slope) of GG at supine was significantly higher than that at sitting, while in TA there was no significant difference of slope between two positions. Conclusion We conclude that during reverse sniff, 1) both GG and TA contribute for producing RSNEP, and 2) GG activity is more influenced by posture than TA activity. This work was supported by MEXT of Japan KAKENHI (2350061). Diaphragmatic rupture due to blunt thoracic trauma is a rare entity. There is no spesific symtom in these patients. We here want to present a case with diaphragmatic rupture that is seen rare after a blunt thoracic trauma. 50 year old male patient had a history of falling from a 4 meters of height three days ago. After the trauma, no surgical pathology had been found and was given analgesic treatment. He was admitted to our clinic because of no relieving of pain, in addition increasing of pain. The physical examination of the patient revealed no abnormal findings except pain in his right lumbal region on palpation. The plain roentgenogram of the patient was reported normal. As suspecting a diaphragmatic injury computed tomography was performed. Computed tomography revealed isolated right posterolateral diaphragmatic rupture. Surgery was advised to the patient. Suspecting diaphragmatic injury is the mainstay in diagnosis of diaphragmatic rupture. Progressive herniation can occur if the rupture is diagnosed late. If not treated on time, strangulation of the abdominal organs can ocur that leads to a lifetreating status. In order to prevent traumatic patients from such complications, diaphragmatic rupture should be kept in mind in trauma patients. Pneumomediastinum is defined as the presence of free air in the mediastinum. Trauma plays an important role in the etiology but it may occur spontaneously. The most common syptoms are; swelling due to subcuthaneous emphysema, chest pain, dispne and hoarseness. Mostly this pathology recovers spontaneously and it rarely requires surgical intervention. Herein we aim to present 6 pneumomediastinum cases that we followed in our clinic between 2004 and 2012. The mean age of patients was 21.5 (20-24 years). The most common complaints of patients; neck pain, swelling at the neck and upper parts of the body and dispnea. None of the patients described trauma history. One patients had a history of swelling of the neck and arms a few times. Four of six patients were investigated with endoscopy and FOB and no pathology has been found. Four of patients regressed spontaneously. One patient who presented with pneumothorax and pneumomediastinum after a status epilepticus attack, was treated with chest tube. One of our patients was severly disturbed due to subcuthaneous emphysema. We placed intra venous catheters subcuthaneously to infra and supra clavicular regions, in order to purge free air. The mean hospitalization time was seven days (5-10 days). Primary spontaneous pneumomediastinum is a rare pathology. Most of the patients regress spontaneously at the first week with out the need of surgical intervention but a close follow-up is important. We think additional endoscopic screening tests will not provide a significant benefit for diagnosis and follow-up of these patients. Reexpansion pulmonary edema is a rare complication that occurs after reexpanding the collapsed lung by the factors such as pneumothorax, pleural effusion and atelectasis. More than 72 hours collapsed lung and rapid reexpanding are the most important risk factors. We aimed to present a case that observed in our clinic. A 20-year-old male patient presented to our clinic with left-sided chest pain 3 days after the onset. In his medical history he was treated two times for spontaneous pneumothorax last year. In his physical examination, breath sounds diminished on the left side. Chest X-ray revealed that his left upper lobe partly and lower lobe totally collapsed. Left tube thoracostomy was performed than clamped. While safety reexpansion was being performed, the patient complained from dyspnea. Oxygen saturation level was %80-85. pO2 pressure was measured as 68.8 mmHg in blood gas. Control chest X-ray revealed acute pulmonary edema on the left lung. The patient lay on the right side. The patient treated with diuretics, oxygen and fluid restriction. The symptoms began to decline after 6 hours. At 8. hour, pO2 pressure level was measured as 87.9 mmHg in the blood gas. Edema significantly regressed at 24th hour chest x-ray. VATS was performed at 3rd day of the tube thoracostomy. The patient was discharged postoperative 14th day and no complication occured. Reexpansion pulmonary edema is a rare complication with high mortality if not correctly evaluate. If the lung collapses for a long time, RPE should be considered and we should concentrate on possible findings. Neurofibromatosis (von Recklinghausen disease) is a genetically-inherited disorder in which the nerve tissue grows tumors (neurofibromas). Desease is characterized with neurofibromas, cafe au lait spots and lisch nodules. We aim to present a neurofibromatosis case with massive chest wall involvement.21 year old -male patient, admitted with chest wall deformity, skin lessions, the complaint of swelling and pain in the back. The disease started in childhood with the appearance of axillary skin hyperpigmented lesion. A swelling appeared on his back in 2002 and it started to increase in size. The lesion was resected in 2004 and pathological diagnosis was neurofibroma. Physical examination: asymmetric deformity on the right side of the chest wall; Big cafe-u lait spots; Multiple spots the average diameter of 3 cm at other parts of the body. When we evaluated the Thorax CT we have seen right side of the chest wall was involved by the neurofibromas and the concomitant ribs were massively deformed. Multiple lisch nodules were detected in ophtalmic examination. No pathological findings detected on brain MRI and no significant restriction was found in pulmonary function test. The patient is in follow-upThe patient described here is a very typical case of neurofibromatosis. Multiple systematic symptoms may ocur on theese patients. As in our case, a detailed investigation is required for NF patients, because of the risk for generalized involvement of other organs. And because of malignant potential, these patients must be followed up closely. Dermatofibrosarcoma protuberans (DFSP) is a rare, slow groving soft tissue tumor that originated in the dermis. Pulmonary metastasis can be seen especially in fibrosarcomatous variant of DFSP. Wide surgical resection is recommended for the treatment but local recurrence rate is high. We aimed to present our dermatofibrosarcoma with bilateral multiple pulmonary metastasis case which is rarely seen. A 23-year old male patient was consulted to our clinic for bilateral pulmonary multiple nodules. In his medical history: When he was 8; a tumor was resected from his right suprascapular region and it was reported as fibrohistiocytic tumor. At the age of 22; a tumor occured on the same region and then resected again. His last histopathological result was reported as The fibrosarcomatous variant of dermatofibrosarcoma protuberans (FS-DFSP) The patient underwent to bilateral thoracotomy at different seances.12 nodules from right lung and 21 nodules from left lung were resected. All of them were reported as DFSP metastasis. The patient was discharged postoperative 7th day and no complication occured. Although DFSP is a locally agressive and low grade tumor; fibrosarcomatous variant of DFSP has high local recurrence and distant metastasis rate. Distant metastasis occurs with local recurrence. That's why cases with recurrence and fibrosarcomatous variant, should be examined more carefully for pulmonary metastasis.

ETSUHIRO NIKKUNI, RITSUKO ARAKAWA, TOSHIYA IROKAWA, HIROMASA OGAWA, HAJIME KUROSAWA Department of Occupational Health, Tohoku University Graduate School of Medicine, Sendai, Japan

Head-up postures (30-60 deg) are commonly used for respiratory care and rehabilitation to relax abdominal muscles, partly for the easy breathing in immobile patients. However, whether the ventilatory impedance is decreased during the postures are not well known. In this study, respiratory system resistance (Rrs) and reactance (Xrs) are evaluated during 4 postures from supine to upright using forced oscillation technique (FOT) in 13 healthy subjects (Age: 23.4 ± 3.5, Male = 13). Following tidal quiet breathing that included 5 stable respiratory cycles, R5, R20 (Rrs at 5 and 20 Hz), and X5 (Xrs at 5 Hz) were assessed using a commercialized FOT apparatus (MostGraph-01, Chest MI, Inc, Tokyo, Japan), in which multi-frequency pulse waves (hanning) at the interval of 0.25 sec were used to oscillate the lung. Vital capacity (VC) and inspiratory capacity (IC) were assessed using a conventional spirometry (HI-801, Chest MI, Inc, Tokyo, Japan). FOT and spirometry were performed at 4 postures, including supine (0 deg), head-up (30 deg, 60 deg), upright (90 deg) positions, in random orders. The more increased degree of head-up, the more decreased R5 and R20 (ANOVA: p < 0.001) and increased X5 (p < 0.05). R5 and R20 at 90 deg were significantly lower than those of the other 3 positions (p < 0.01). Although IC linearly decreased from the upright to the supine postures (ANOVA: p < 0.001), the changes of R5, R20, and X5 did not seem linear. We speculated that the changes in Rrs during the head-up reflect not only the lung volume but also other mechanisms such as the upper airway collapse by gravity. Results Out of 62 subjects who underwent CPET,32 patients with maximal exercise test were analysed. Of those 32 subjects, mean work rate was 119.22(35-210), mean Vo2 max was 22.5 ml/kg/min (9.5-37.8). 6 subjects (18%) had normal exercise tests. None had health care visits related to dyspnea over 2 years.19 subjects (59%) had cardiac limitation or deconditioning with mean Vo2 max 20.9 ml/kg/min (11.36-28.88), mean anaerobic threshold 28.58% (17-48), and mean O2/HR of 8.74(5-13).5 subjects had no cardiac evaluation.13 subjects had cardiac evaluation with two abnormal findings (one ischaemia and one heart failure). Seven subjects (22%) had deconditioning with mean Vo2 max 25.9 ml/kg/min (9.55-32), mean and Anaerobic threshold 34.5% (27-46). One subject had normal cardiac evaluation. None had health care visits related to their dyspnea over the 2 years. In our study, among those with maximal exercise testing, 2 subjects with normal study group had cardiac evaluation, 1 with cardiac limitation group had CT thorax revealing TB and 1 in the deconditioning group had coronary angiogram. The remaining 87% (28/32) either had targeted investigations pertaining to the limitation or did not undergo any investigation with 2 year stability. Conclusion CPET is a useful tool to channel out subsequent evaluation for dyspnea in a focused manner thereby limiting the amount of investigations that have to be undergone otherwise in the outpatient setting. Purpose We intended to determine the clinical effectiveness and accuracy of infrared thermal imaging (IRTI), a novel technique for noninvasive imaging detection of vessel function, in diagnosing lower limb DVT in humans. Methods 64 DVT patients and 64 non-DVT volunteers who had been definitely diagnosed by Doppler vascular compression ultrasonography (CUPS) or angiography enrolled in this research. We utilized IRTI sensor to detect the lower limbs of the 64 DVT patients. IRTI pictures captured were studied by qualitative pseudocolor analysis and quantitative temperature analysis in terms of mean area temperature average (Tav) and mean linear temperature (Tla) in the region of interest (ROA) as shown in IRTI. The differences in Tav and Tla between the DVT and non-DVT sides in IRTI of each patient as well as TDTav and TDTla between DVT patients and non-DVT volunteers were compared. Results Qualitative pseudo-color of IRTI analysis revealed that the bilateral infrared presentation and distribution characteristics (PDC) were visibly asymmetry and that there were abnormally high temperature districts at the DVT side, which was assumed as positive. Out of the 64 definite DVT patients, 62 were positive in IRTI (96.88%). Of the IRTI positive cases, 53 (82.81%) had infrared PDC at coincident DVT situs and 9 case (14.52%) did at coincident DVT sides compared with the results of CPUS or angiography. There were highly statistically significant differences both between DVT side and non-DVT side in DVT group (p < 0.01) and between DVT group and non-DVT group (p < 0.01). Conclusion IRTI can be used in detecting and screening DVT effectively and accurately. HEMODYNAMIC RESPONSE TO VASODILATORS   AKANE KUROKI, TAKAHIRO SATO, ICHIZO TSUJINO, AYAKO IGARASHI,  HIROSHI Background A certain subset of group 3 pulmonary hypertension (PH) patients are known to exhibit advanced, or out-of-proportion, PH. For this population, vasodilator treatment is not generally recommended because of the lack of evidence and possible deterioration of ventilation/perfusion mismatch. Objective To investigate the efficacy and safety of vasodilator treatment in patients with out-of-proportion group 3 PH. Subjects Since 2010, we have treated 5 consecutive patients with progressive dyspnea due to such PH, using sildenafil alone (n = 3), sildenafil plus beraprost (n = 1) or sildenafil plus bosentan (n = 1). The underlying pulmonary diseases were early-onset chronic obstructive pulmonary disease (n = 1), rheumatoid arthritis-associated interstitial pneumonia (n = 1), cystic lung disease (n = 1) and combined pulmonary fibrosis and emphysema (n = 2). Results Before treatment, all patients presented with progressive dyspnea, and demonstrated increased mean pulmonary arterial pressure (MPAP) (44 ± 7 mmHg) and pulmonary vascular resistance (PVR) (907 ± 177 dyn*s*cm −5 ). Vasodilator treatment was well-tolerated and, at the follow-up assessment 3-4 months later, all patients noted less dyspnea and significant reduction in MPAP (34 ± 5 mmHg, −22 ± 14%) and in PVR (546 ± 191 dyn*s*cm −5 , −41 ± 11%). Pulmonary oxygenation was deteriorated in 1 patient, but was improved or not significantly changed in the remaining 4 patients. Conclusions All five patients with progressive group 3 out-of-proportion PH responded favorably to vasodilators. Vasodilator therapy, particularly using sildenafil, may represent a promising option in this population when introduced in the early phase of disease. Background It is generally recognized that there is narrowing and diminution of the small vessels on pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Previous studies have shown that these vascular alterations could be assessed by the cross-sectional area of small pulmonary vessels (CSA) on high-resolution CT (HRCT) in patients with COPD. However, it is unknown whether there is a correlation between CSA and hemodynamics in patients with CTEPH. Aims We retrospectively evaluated the relationship between the CSA on HRCT and hemodynamics measured by right heart catheterization (RHC). Materials and Methods 53 patients (61 ± 12 yrs, 14 male) with proven CTEPH underwent non-enhanced 64-slice HRCT and RHC. The HRCT images with 0.5 mm section thickness and 10 mm spacing were selected from all of the CT images in each patient. Using a semiautomatic image-processing program (Image J), CSA less than 5 mm 2 and 5-10 mm 2 , and total lung area were measured, and the percentage of the total CSA less than 5 mm 2 and 5-10 mm 2 for the lung area (%CSA<5 and %CSA5-10, respectively) were calculated. The correlations of %CSA with hemodynamics measured by RHC were evaluated. Results Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) from RHC were 41 ± 10 mmHg and 8.3 ± 3.2 Wood Units, respectively. %CSA<5 and %CSA5-10 were 1.085 ± 0.170% and 0.443 ± 0.088%, respectively. The correlation coefficients of %CSA<5 with mPAP and PVR were −0.46 (P < 0.001) and −0.60 (P < 0.001), respectively. The correlation coefficients of %CSA5-10 with mPAP and PVR were −0.24 (P = 0.09) and −0.37 (P = 0.006), respectively. Conclusions This study suggests that %CSA<5 measured on HRCT is inversely correlated with PVR and can be used to evaluate hemodynamics in CTEPH subjects. Methods In this Cross Sectional study, PH was screened by Doppler echocardiography in 100 patients one hour following dialysis and done by one independent operator without knowing clinical background of patients. History taking, physical examination, and secondary data from medical records including laboratory data were included. Results Pulmonary hypertension was detected in 27 patients (27%). Of those with PH, brachial AV shunt was seen in 21 patients (77.8%) with diabetic nephrophaty as the common etiology of this group was seen in 10 patients (37%), and mean PAP was 36 ± 20.6 mmHg. Cardiac output > 5 l/min was seen in 13 patients (48.1%) with EF > 50% seen in 18 patients (66.7%). The determinant factors in this study was left ventricular diastolic dysfunction (p:

Background and Aim of Study To evaluate the reliability on phase contrast(PC) MR imaging and CT in prediction of pulmonary hypertension (PH) in patients with suspected PH.

The study protocol was approved by the institutional review board. The subjects were forty-seven patients who had or suspected of having PH (30 male and 17 female; mean age, 69.8, 24 with interstitial pneumonia, 14 with heart failure and 9 of other diseases, including chronic pulmonary arterial thromboembolism and so on). Right heart catheterization (RHC), cardiac magnetic resonance (MR) imaging, and chest CT were performed. Mean velocity, minimum area, and maximum area of mean pulmonary artery (MPA) were measured on phase-contrast MRI (PC-MRI). On CT images MPA diameter was obtained. We also measured the volume of fibrosis and normal lung using computer-aided system. These parameters were correlated with mean pulmonary arterial pressure (mPAP) measured by RHC using Pearson's correlation analysis. The area under the receiver operating characteristic (ROC) curve were constructed to assess the predictive value of these parameters in the identification of PH. . Other than these candidates may cause drugs-associated PAH. Methods A 38-year-old woman took the herbal medicine "bofutsushosan" for two weeks then stopped taking it due to general malaise and exertional dyspnea. The cause of exertional dyspnea was seeked to find. Results After discontinuation of bofutsushosan, dyspnea continued for three months and echocardiography revealed tricuspid regurgitation pressure gradient of 40 mmHg, suspecting the existence of PH. A chest roentgenogram showed prominent hilar pulmonary artery with CTR of 51.5%. 6MWD was 486 m with lowest oxygen saturation of 89%. The perfusion scans were normal and contrast CT scans did not show pulmonary embolism. Right heart catheterization revealed elevated PAP of 64/21 with mPAP of 41, pulmonary capillary wedge pressure of 9, and a CI of 4.67, resulting in calculated PVR of 326. She was treated with oxygen and diet therapies. Her dyspnea on exertion gradually disappeared after discharge, and 8 months later she did not need oxygen. Her BNP was normalized and a chest roentgenogram revealed an improved cardiac enlargement. She was admitted to our hospital for revaluation 18 months after first catheterization. Right heart catheterization revealed normal PAP of 26/8 (15) mmHg, CI of 3.70 and PVR of 102. Conclusion This is the first report of spontaneously remitted PAH induced by herbal medicine. This report may provide clinicians the important information that early suspicion and recognition of pulmonary hypertension are needed for the patients with exertional dyspnea, who took herbal medicine, to avoid further deterioration. Pulmonary arterial hypertension (PAH) has become an important topic for basic and clinical research in recent years. Morphologic research has shown that specific PAH-lesions are located in the small arteries of the lobule and correlate with hemodynamic measurements. However, it still remains to be shown how pathological changes of the small arteries in the lobule develop into PAH. Based on both the fractal properties of the pulmonary arterial tree and asynchronous phasic contractions of the lobular arterial muscles under the evenness of pulmonary capillary pressure (PCP) in the lung, we have constructed an integrated model of pulmonary circulation that demonstrates a mathematical relationship between mean pulmonary arterial pressure (MPAP) and cardiac output (CO). Using the relationship between MPAP and CO, we have been able to explain the pathogenesis of pulmonary hypertension (PH) in terms of statistical changes between regional and temporal perfusion in the lung. In order to clinically detect the early stages of PH, we have suggested that it is important to establish pulmonary functional imaging of regional and temporal perfusion. Background and Aim of Study High altitude pulmonary edema (HAPE) is a non-cardiogenic life-threatening pulmonary edema that characterized by exaggerated hypoxic pulmonary hypertension. The pathogenesis remains to be conclusively elucidated and genetic polymorphisms are highly proposed to be associated with HAPE. The aim of this study is attempt to identify the candidate human genes those might associate with the development of HAPE. Methods The case group included 53 Japanese HAPE susceptible subjects who had developed HAPE during climbing mountains higher than 2,500 m. The control group enrolled 67 Japanese HAPE resistant subjects who were elite alpinist and did not develop HAPE during their histories. A case-control association study was performed using 400 polymorphic microsatellite markers by PCR and sequenced by Gene Scan software. Results Nine markers showed statistically significant associations with the susceptibility to HAPE, and three markers showed significant associations with the resistance to HAPE. We also evaluated the association of HAPE with six single nucleotide polymorphisms (SNPs) in inhibitor of metalloproteinase 3 (TIMP3) gene that included a resistance microsatellite marker (D22S280). One of six SNPs in TIMP3 gene (rs130293) was significantly associated with the HAPE susceptibility (P < 0.0005). Conclusion This is the first genomewide association study in HAPE. It revealed several candidate genes in associations with HAPE. Our findings also elucidated that the polymorphism of TIMP3 gene was significantly associated with the susceptibility to HAPE. This study provides the first evidence that the development of HAPE may be determined by the interaction of multiply genes and TIMP3 may influence the risk for HAPE. We report here a case of a previously healthy 16-year old girl was treated with anti-TB drug combination (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol) for TB adenitis and noted resolution. However, 40 days after drug intake, flu-like symptoms, pruritic erythematous maculopapular rashes, and eventually dyspnea developed. Vital signs were stable but patient was febrile at 40C. She had multiple erythematous to hyperpigmented macules and confluent patches over the face, trunk and extremities; dryness and slight scaling on the lips, but no conjunctivitis. She had anicteric sclera, supple neck, multiple cervical lymphadenopathies and bibasal crackles. There was eosinophilia and transaminitis. Peripheral blood smear showed leukocytosis without atypical lymphocytosis. Antinuclear antibody (ANA) was negative. Arterial blood gasses revealed uncompensated respiratory alkalosis with moderate hypoxemia. PaO2/FIO2 ratios were less than 200 consistent with ARDS. Discussion Our patient was diagnosed as a definite case (final score 7) of DRESS syndrome based on the postulated scoring system by Kardaun et al. Clinical features were typical -fever more than 38.5C, lymphadenopathy, eosinophila more than 1,500/uL, skin rash more than 50% suggesting DRESS, biopsy suggesting DRESS, and visceral involvement (lungs and liver). Significant improvement of skin lesions was noted after intravenous hydrocortisone, antimicrobials, and antihistamines were given. However, fever persisted, desaturations and hypotension ensued. Diffuse bilateral lung infiltrates progressed. Patient died. To our knowledge, because of its rarity (incidence of 1 in 1,000 and 1 in 10,000 exposures), this represents the first reported case of DRESS syndrome due to anti-TB drugs in the Philippines. Overall mortality in DRESS syndrome is 10%. Conclusion General awareness and pharmacovigilance are important due to the severity and life-threatening potential of this type of drug reaction. We proposed an algorithm in the diagnosis and management of DRESS.

The addition of tiotropium provides bronchodilation and reduces exacerbations in patients with severe asthma (Kerstjens et al. NEJM 2012; 367:1198-207) . Subgroup analyses were performed to determine whether this positive effect was limited to definable subgroups of patients. Methods Eligible patients had a ≥5-year history of asthma, and had experienced ≥1 exacerbation in the previous year. Time to first severe exacerbation from the pooled data after 48 weeks was a primary end point. Secondary end points included time to first episode of asthma worsening. Subgroup analyses of time to first severe exacerbation were performed in groups defined by baseline characteristics, including age, allergic status, smoking status and reversibility. Results 912 patients were randomised: 456 received 5 μg tiotropium via the Respimat® Soft Mist TM Inhaler and 456 received placebo once daily for 48 weeks. In the total study group, the time to first severe exacerbation was increased by the addition of tiotropium (risk reduction 21%; hazard ratio 0.79; p = 0.03). The time to first episode of asthma worsening was increased in the tiotropium group compared with placebo (risk reduction 31%; hazard ratio 0.69; p < 0.001). Subgroup analyses showed that neither the time to first severe exacerbation nor the time to first episode of asthma worsening was dependent on baseline characteristics (no significant interactions). Conclusions The increase in time to first severe exacerbation and first episode of asthma worsening found with the addition of tiotropium was not limited to specific subgroups of patients, including some characteristics that are usually found in patients with chronic obstructive pulmonary disease, such as former smoking, non-allergic status or minimal reversibility. Tiotropium seems effective across a broad spectrum of patients with severe persistent asthma who remain symptomatic and experience exacerbations despite the combination use of moderate-to high-dose inhaled corticosteroids plus longacting beta agonists. Background Chronic eosinophilic pneumonia (CEP) generally responds to steroid therapy. However, relapse frequently occurs and prolonged steroid therapy is needed in such cases. Mast cells play an important role in allergic diseases and interstitial lung diseases. Tryptase released from activated mast cells is associated with intractable pathogenesis. Little is known of the clinical significance on measurement of mast cell tryptase in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia. Methods The BALF from 16 patients with eosinophilic pneumonia [CEP 8 patients, Acute eosinophilic pneumonia (AEP) 4 patients, Drug-induced eosiophilic pneumonia (Drug) 4 patients] was analyzed by B12 a monoclonal antibody-based tryptase immunofluoroassay, which can detect both monomer (inactive from) and tetramer (active form) of both α and β tryptases. The relationship between clinical characteristics and tryptase in BALF was analyzed retrospectively. Results Tryptase in BALF could be detected in 7 patients (CEP 6, AEP 1; the tryptase-positive group), but not in 9 patients (CEP 2, AEP 3, Drug 4). The concentrations of tryptase in the tryptase-positive group were 2.45 ± 0.46 ng/ml in CEP (n = 6, Mean ± SD) and 1.0 ng/ml in AEP (n = 1). The tryptase concentration was significantly higher in CEP than in AEP and Drug (p < 0.05). Recurrence of eosinophilic pneumonia was seen in 7 patients with CEP, but not AEP and Drug. Six patients with CEP had asthma history. Of them, one patient had allergic bronchopulmonary aspergillosis and another one had chronic eosinophilic sinusitis. Conclusion Tryptase in BALF can be detected in patients with CEP. The tryptase-positive patients with CEP tended to relapse and have complication of asthma. Mast cell tryptase may be associated with intractable pathogenesis in CEP. This work was supported in part by grant No. 22590844 from the Japanese Ministry of Education, Science and Culture.

Introduction Eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss syndrome), a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis, is often effectively treated with corticosteroids. However, relapse rates are high and, for unknown reasons, some EGPA patients suffer frequent relapses after entry into initial remission. Regulatory T (Treg) cells and B cells are implicated in the development and progression of EGPA. We explored the influence of Treg cells and a co-stimulatory factor present on B cells on the development and course of EGPA. Methods We studied 45 EGPA patients (19 of whom experienced frequent relapses and 26 of whom seldom relapsed) and 67 (control) patients with general asthma. We determined the counts or percentages of whole-blood cells exhibiting the following characteristics: FOXP3 + cells among CD4 + Treg cells; CTLA-4 + cells among CD4 + /CD25 + Treg cells; and CD27 + , CD80 + , CD86 + , or CD95 + cells among CD19 + B cells. We also measured serum IgG concentrations. Results Compared with patients with asthma or seldom-relapsing EGPA, frequently relapsing EGPA patients with active disease exhibited decreased counts of Treg cells and increased percentages of B cells that scored as CD80 + , CD27 + , or CD95 + . Patients with frequently relapsing EGPAhad increased percentages of CD27 + and CD95 + B cells, and fewer CD19 + B cells, than did patients in the other two groups. Lower CD19 + B cell counts were associated with reduced Treg cell counts and a lower serum IgG concentration. Conclusion In patients with frequently relapsing EGPA, decreases in Treg cell numbers and increased percentages of activated B cells may induce apoptosis of B cells.

The nitrogen (N2) single-breath washout (SBW) test is a measure of ventilation distribution inhomogeneity and also a small airway function that offers complementary information to spirometry; however, the relevance to the forced oscillation technique (FOT) and pulmonary emphysema in COPD is not fully understood. We hypothesized that pulmonary functions, forced oscillatory parameters, and emphysema extent would contribute independently to the results of the SBW test. In this crosssectional study we assessed the relationship between the phase III slope (delta N2) derived from N2 SBW and these parameters. Methods Spirometry, lung volumes, N2 SBW, and the broadband frequency FOT using MostGraph-01 were performed in 56 patients with stable COPD. We used respiratory system resistance at 5 Hz, resonant frequency, and the difference between inspiratory and expiratory respiratory system reactance at 5 Hz as the expiratory flow limitation (EFL) index. Emphysema extent was measured by high-resolution computed tomography and scored.

The median (range) value of FEV1 was 52.6 (17.8-108.0) % predicted; forced vital capacity, 81.4 (34.9-144.0) % predicted; delta N2, 4.36 (1.68-13.71) %N2/L; respiratory resistance at 5 Hz, 4.02 (1.83-7.64) cmH2O/ L/s; resonant frequency, 10.87 (4.46-27.07) Hz; EFL index, 0.63 (−0.47-5.25) cmH2O/L/s; and emphysema score, 10 (0-23). In multiple regression analyses, the delta N2 was independently predicted by forced vital capacity, resonant frequency, and emphysema score (R2 = 0.57, p < 0.0001). Conclusion The degree of ventilation inhomogeneity derived from N2 SBW is independently predicted by spirometry, lung mechanics, and the degree of emphysema.

AKINORI EBIHARA 1 , ASUKA NAGAI 1 , RURIKA HAMANAKA 2 , TOKUZEN IWAMOTO 1 , ICHIRO KUWAHIRA 1 1 Pulmonary Medicine, Tokai University Tokyo Hospital, 2 General Thoracic Surgery, Tokai University Tokyo Hospital, Japan Background Cardiovascular events are an important part of the comorbidities and complications in COPD patients. Analyzing the data of the ratio of serum Eicosapentaenoic Acid to Arachidonic Acid: EPA/AA and Ankle Brachial Pressure Index: ABI, which were useful as an indicator of arteriosclerosis, we examined the correlation between them in this study. Methods A total of 149 subjects, male 84, female 65, were enrolled into the study after informed consents were obtained until January 2013 from May 2007 in Erimo town clinic in Hokkaido. We divided potential subjects into three groups: Group 1a had a history of COPD and sever exposure to tobacco smoke; Brinkman Index more than 800, Group 1b had a history of COPD and the other exposure history, Brinkman Index less than 800, and Group 2 had a history of other diseases without COPD, such as diabetes, hypertension, and hyperlipidemia. Results G1a was 38 subjects, male 28, female 10, G1b was 35 subjects, male 19, female 16, and G2 was 76 subjects, male 37, female 39, respectively. ABI in G1a: G1b: G2 0.81 ± 0.48: 0.83 ± 0.24, 0.91 ± 0.21, EPA/AA in G1a: G1b: G2 0.41 ± 0.13: 0.42 ± 0.11: 0.47 ± 0.16. G1a demonstrated significant decline in ABI and EPA/AA, when compared with G2. However there was no significant difference in the data between G1b and G2. Conclusion In COPD patients with severe exposure to smoke, significant decline in ABI and EPA/AA was observed. The results indicate that these patients have an increased risk of smoke-related cardiovascular diseases such as acute myocardial infarction and stroke.

Introduction Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease caused by smoking in which pathogenesis remains unclear. Although chronic inflammatory response from COPD affects lungs with significant systemic consequences, there has been few studies about the correlation between clinically useful inflammatory biomarker and exercise capacity. This study was designed to find the relationship amongst pulmonary function test, inflammatory biomarkers such as lactate dehydrogenase (LDH) and blood urea nitrogen (BUN), and patients' exercise capacity. Subjects and Method From March 2009 to December 2010, 33 patients with COPD recorded daily number of steps for 4 weeks with the pedometer. The patients who recorded daily number of steps for more than 2 weeks were enrolled and data from 3 patients were excluded due to inadequate recordings. Obtained data were analyzed dividing dates into 1) 14-day average, 2) weekdays, and 3) weekends and the correlation of the number of steps with serum LDH & BUN level were evaluated. Results There was no correlation between exercise capacity of patients with COPD and serum LDH, BUN levels. Correlation was not found between serum LDH level and the average number of steps for 14 days (p = 0.640), the average number of steps on weekdays (p = 0.393), and the average number of steps on weekends (p = 0.107). There was also no correlation between serum BUN level and the average number of steps for 14 days (p = 0.057), the average number of steps on weekdays (p = 0.060), and the average number of steps on weekends (p = 0.097). No correlation was found between the exercise capacity measured by the pedometer and FEV1 either. Conclusion There was no correlation amongst preexisting pulmonary function test markers, inflammatory biomarkers such as LDH & BUN and exercise capacity in COPD patients. Background The morphological change related to chronic obstructive pulmonary disease (COPD) occurs from mild stage of COPD. Although overinflated lung in COPD is known to be related to morphological tracheal deformity, relationship between morphological change of trachea and lung volume parameters in mild-to-moderate stage of COPD has yet not been determined. Thus, our aim was to investigate the association of tracheal index (TI) with lung function parameters including those related to lung volume in COPD patients with mild-to-moderate airflow limitation. Materials and Methods A retrospective study was conducted with 193 mildto-moderate airflow limitation patients and 193 subjects with normal lung function as control group. Two independent observers measured TI at three different anatomic levels on chest radiographs and CT. Results Compared with the control group, TI was significantly reduced, and saber-sheath trachea was more frequently observed in COPD patients with mild-to-moderate airflow limitation at all three different trachea levels. TI had apparent inverse correlations with total lung capacity, functional residual capacity, and residual volume, which were particularly notable in TI measured at the upper margin of the aortic arch on chest CT. Even after adjustments of covariates, this association persisted. Conclusions TI is reduced even in mild-to-moderate COPD patients, and TI measured on chest CT shows significant inverse relationships with all lung volume parameters, suggesting that tracheal morphology might change from early stages of COPD. Background Airflow obstruction in COPD is caused by chronic inflammation and permanent structural changes in the smaller airways and lung parenchyma. Current studies on anti-inflammatory treatments for COPD have focused on targeted inhibition of phosphodiesterase 4, the major enzyme of cAMP in inflammatory cells. Roflumilast, a targeted inhibitor of phosphodiesterase 4, reduces inflammatory products such as leukotriene B and TNF-a in inflammatory cells. Methods The patients considered were those >40 years old with a diagnosis of moderate to severe COPD (confirmed by a post-bronchodilator [FEV1]/FVC ratio <0.70 and post-bronchodilator FEV1 <50% of predicted value). All patients were current or former smokers with a minimum smoking history of at least 20 pack years, and have history of chronic productive cough. The intervention being tested is Roflumilast in combination with LABA, and the search strategy focused on RCTs in which an experimental group included Roflumilast with LABA vs. LABA with placebo. The primary efficacy endpoints observed were change in pre-bronchodilator FEV1 from baseline to each post randomisation visit. Secondary endpoints included postbronchodilator FEV1, pre-and postbronchodilator FVC and transitional dyspnea index. Statistical analyses were performed using the RevMan computer software. Results Three thousand nine hundred and five patients were included in the three trials that reported change in mean prebronchodilator FEV1 from baseline to each post randomisation visit. LABA with Roflumilast was noted to have significant difference when compared with LABA and placebo in improving prebronchodilator FEV1 (p < 0000.1). Secondary outcomes tested also showed significant difference in comparing LABA with Roflumilast vs. LABA with placebo (p < 0000.1). Conclusion Roflumilast improves lung function in patients with moderate-tosevere COPD who are already being treated with LABA. The use of oral, once daily anti-inflammatory agent instead of inhaled corticosteroids as concomitant therapy to LABA has advantages, such as increased compliance and no demonstrable increase risk of pneumonia.

Plasma levels of inflammatory protein, cathepsin B and its naturally inhibitory protein cystatin C were examined in chronic obstructive pulmonary disease (COPD) patients during and two weeks as well as 8 weeks after acute exacerbation (AE). The changes of of plasma levels of these proteins were evaluated to speculate whether they are well correlated with the inflammatory statuses of COPD exacerbation. 46 COPD patients, including 44 male and 2 female, were included in this study. Plasma were collected in three different times, i.e., during, and 2 weeks as well as 8 weeks after AE. 18 healthy subjects, including 10 male and 8 female, were studied as control. Enzymelinked immunosorbent assay(ELISA) wad use to measured the plasma levels of the study proteins. The plasma levels of cathepsin B were significantly higher in COPD patients at 2 weeks and 8 weeks after AE when compared with those of healthy subjects. In COPD patients, the plasma levels of cathepsin B were significantly higher at 2 weeks after AE than those at the time of AE. The plasma level of cystatin C showed significantly higher than the plasma levels of healthy subjects at time of AE, also 2 weeks and 8 weeks after AE. However, there was no significant difference between the time of AE and 2 or 8 weeks after AE. In conclusions, the persistently significant higher plasma levels of cystatin C in COPD patients not only on AE but also at 2 and 8 weeks after AE than those in healthy subjects might represent a chronic inflammatory status in COPD. Moreover, plasma level of cathepsin B significantly increased at 2 weeks after AE and which returned to be non-significant at 8 weeks after AE in COPD patients. Aim Tai Chi is an ancient Chinese martial art which involves a series of slow and controlled movements. It is practised increasingly in the West as a mean of exercise. The aim of this study was to determine the acceptability of Tai Chi by Caucasian people with COPD who had completed a 12-week Tai Chi training program. Methods Participants with COPD who finished a twice weekly, 12-week short-form Sun-style Tai Chi training program, completed a survey of eight questions. Each question was answered by putting a stroke on a 10 cm visual analogue scale, with a higher score indicating a better experience. The number of supervised training sessions attended during the 12-week period and the number of unsupervised home practised days were also reported. Results Twenty-three participants, all Caucasians with no previous experience of Tai Chi, completed the survey (mean (SD) age 74 (8) years, mean FEV1% 59 (17)% predicted). Participants attended 21 (2) supervised training sessions out of a possible 24 sessions and practised 4 (1) days per week for unsupervised home training. Results for four of the eight survey questions: 1. 'How enjoyable was the Tai Chi program?' (mean (SD) score 8.9 cm (1)); 2. 'How helpful was the Tai Chi program in improving physical fitness (7.9 cm (2)), balance (7.9 cm (2)) and shortness of breath?' (7.0 cm (2)); 3. 'How hard was it to remember the Tai Chi movements?' (5.3 cm (3)) 4.'Would you continue Tai Chi training as your regular exercise regimen?' (8.4 cm (2)). Conclusion Participants reported that short-form Sun-style Tai Chi was a highly enjoyable exercise which improved their physical fitness, balance and shortness of breath. Participants were also very adherent to the supervised and unsupervised training sessions. Importantly, participants indicated that they would continue Tai Chi as their regular exercise regimen. Results Patients (n = 584; mean age 64.1 ± 8.8 years; 73% GOLD grade III disease) were randomised to BUD/FORM + IB+T-SR (n = 292; full analysis set [FAS], n = 290) or IB+T-SR (n = 292; FAS, n = 292). There were no differences in baseline characteristics between groups. The improvement in pre-dose FEV1 from baseline was significantly greater with BUD/FORM + IB+T-SR than with IB+T-SR alone, with an increase of 6.9% (95% CL: 4.3, 9.6%; p < 0.001).

There was a 43% reduction in exacerbation rate (rate ratio 0.565, p = 0.0425) and a 6.3 point improvement in SGRQ-C (−11.3 vs −4.6, p < 0.0001) with the addition of BUD/FORM. Few patients experienced adverse events (AEs) related to treatment (1.0% BUD/FORM + IB+T-SR; 0% IB+T-SR), or discontinued due to AEs (1.0% BUD/FORM + IB+T-SR; 2.1% IB+T-SR). Conclusions The addition of BUD/FORM to IB+T-SR was well tolerated and associated with clinically significant benefits in lung function, exacerbation rate and health-related quality of life in Chinese patients with severe COPD. This study demonstrates the benefit of BUD/FORM used in combination with a widely used local regimen. Funding AstraZeneca. Background Mastering effective breathing and sputum clearance techniques are essential for patients with COPD. Moreover, enhancing patients' self-management skills could contribute to reduce hospital readmissions. In order to facilitate the bedside education, the physiotherapy department of North District Hospital had developed a patient education package in 2010. To evaluate the effectiveness of this learning process, an assessment chart known as "Breathing Control and Bronchial Hygiene" (BCBH) score was devised and patients' performance was used to correlate with hospital readmissions. Methods All COPD patients referred for Respiratory Collaborative Care Team's service received an assessment and daily bedside coaching with educational aids. Review was made before patients' discharge. The chart evaluates the management of exacerbation (6 points), techniques of breathing control (8 points) and sputum clearance (4 points) giving a total score of 18. Results From November 2010 to November 2012, 468 patients were assessed. Majority (78%) were elderly (aged 70 or above). Mean total scores increased from 5.7 at baseline to 9.1 at discharge. Baseline mean scores were lower for the elderly (5.4) than those age < 70 (6.6). At discharge, scores improved to 8.4 for the elderly and 11.7 for those age < 70. Hospital readmission rates within 28 days were 25.3% and 17.6% respectively. Conclusion This study shows that BCBH scoring could be used as an objective measure of patient's learning. Patients aged below 70 had higher scores and lower hospital readmission rates. Educating elderly patients is challenging. Although visual aids are incorporated in patient booklets, a certain level of literacy is necessary. Engaging care-givers in the patient education may help to reinforce the techniques learnt. Although further studies are needed to determine the minimal clinically important improvement for the BCBH score, results of the younger group suggest that a score of 12 would be necessary to demonstrate competency.

Background and Aim of Study Chronic obstructive pulmonary disease is a major burden to many healthcare systems worldwide, including Hong Kong. In 2008, the hospitalized COPD inpatients reached 30,935 and it is the fifth leading cause of death in Hong Kong. How to monitor and assess this large patient group is a hot debate in the medical field for years and there is a rather simple tool came up lately, the COPD Assessment Test, CAT score. This questionnaire aims at reflecting the health status of the patients and thus hoping to have a role in assisting patients and physicians in quantifying the impact of COPD on the patient's health status. According to the CAT Development Steering Group, the experts believe that a difference or change of 2 or more units suggests a clinically significant difference in health status. The aim of our study is to see the meaning and application of these 2 units of change in our elderly Chinese COPD patients. Methods All COPD patients coming up for medical consultation are requested to do the CAT questionnaire. As the literacy among our patients is rather low, we unify the protocol that our rehabilitation nurse will read the 8 questions to them and get their scores. All these patients will be asked again by the same nurse after their medical consultations, i.e., about 30 minutes later, without their prior awareness. Results We have interviewed 50 consecutive patients, 24 patients, 48% had changes of their scores with more than or equal to 2 units. Further analysis found that this significant change is correlated to older age, lower education level and frequent hospitalizations in the past 1 year. Conclusion CAT score may not be that applicable in our group of old Chinese COPD patients with low education level. 3 million yet over 90% of them are undiagnosed, therefore there is an urgent need to find these undiagnosed patients and treat them earlier. The COPD Assessment Test (CAT) was developed as a simple patient-completed tool for assessing and monitoring the impact of COPD on health status. It is easy to implement in routine use within Primary Care, we hypothesized that the CAT may have utility for case-finding patients who need to have spirometry to diagnose with COPD in Primary Care. Methods Two multi-center, non-interventional, prospective studies (Study 1 and 2) were conducted in 15 and 17 centers across Japan. Subjects in both studies were aged 40 years or older with smoking history. Subjects in Study 1 had not been diagnosed with COPD but had experienced repeated respiratory tract infections, and subjects in Study 2 routinely visited for their cardiovascular diseases. Subjects completed the CAT prior to lung function testing by handheld spirometry (Hai-checker). We investigated the relationship between CAT score and the airflow limitation. Results CAT score were available from a total 3,062 subjects (2,067 in Study 1 and 995 in Study 2); 88.8% were male and age was 61.5 ± 11.6 years (mean ± SD). Airflow limitation was found in 400 (19.4%) subjects in Study 1, and 269 (27.0%) in Study 2. CAT score in subjects with airflow limitation was higher than subjects without airflow limitation in both studies: 8.3 (95% Confidence Interval [CI] 7.5-9.2) vs 6.4 (95%CI 6.0-6.8) in Study 1, 8.6 (95% CI 7.9-9.2) vs 7.4 (95% CI 7.1-7.6) in Study 2. Conclusion This suggests that the CAT has the potential to identify subjects who need spirometry to diagnose with COPD, particularly in those with a history of frequent exacerbations or comorbidity of cardiovascular disease.

Background and Aim of Study Combination with long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) demonstrate superior bronchodilation compared with LAMA or LABA monotherapy in patients with COPD. Indacaterol, once-daily, inhaled ultra-LABA, has been shown to be effective with moderate to severe COPD. However the efficacy of combination with LAMA and indacaterol is unclear in patients with very severe COPD. The aim of this study was to estimate the efficacy of combination with two oncedaily inhaled bronchodilator, indacaterol and tiotropium, in patients with very severe COPD. Methods S ix Japanese patients with very severe COPD according to Global Initiative for Chronic Obstructive Lung Disease criteria were enrolled. The patients who had been already administered with tiotropium (Handihaler®) 18 μg once daily received indacaterol 150 μg in addition once daily concurrently. The efficacy outcomes were evaluated in spirometry data and health status assessed by COPD assessment test (CAT) at baseline with tiotropium alone and at week 8, 12, and 16 with tiotropium and indacaterol. Results FEV1 at week 8 with tiotropium plus indacaterol was increased in comparison with tiotropium alone in four of six patients. Although one patient dropped out at week 8 because of no improvement, the others kept increasing FEV1 at week 12 and 16. However, there were no statistically significant differences in inspiratory capacity and CAT scores. The combination therapy showed in subjective symptoms remarkable improvement in two patients, no significant differences in three, and getting worse in one. Conclusion The combination therapy of indacaterol and tiotropium increased FEV1 in some parts of patients with very severe COPD. Although it seemed that there was no correlation between the degree of improvement in FEV1 and CAT score, some patients felt remarkable efficacy in subjective symptoms with this combination.

Background and Aim of Study Forced expiratory volume in 1 second (FEV1) in chronic obstructive pulmonary disease (COPD) is known to annually decrease more obviously than normal subjects. However, airflow limitation of COPD is partly reversible, and several drugs for COPD are newly developing. The aim of this study is to evaluate the change of pulmonary function of COPD after added medical treatments and to identify predictors of the change of pulmonary function. Methods We studied 37 patients who visit Kumamoto University Hospital or General Hospital in Kumamoto City with FEV1/FVC less than 0.7, diagnosed with COPD and treated with medication by respiratory physicians more than 1 year. Their clinical backgrounds, pulmonary function tests, lung imaging studies at first visits, treatments, and the latest pulmonary function tests were collected retrospectively from their medical records. The significant predictors of change of FEV1 from first to latest pulmonary function tests were evaluated using multiple regression analysis. Results FEV1 at first visit were 1283 ± 538 ml (56 ± 22% predicted) and that was 68 ± 216 ml increased at latest visit (45 ± 123 ml/year). The significant predictors of favorable courses of FEV1 were 1) less smoking history, 2) higher reversibility by inhalation of short acting inhaled β2 agonist (SABA) at first visit, and 3) use of long acting inhaled β2 agonist (LABA). Conclusion We confirmed that the COPD patients having higher reversibility by inhalation of SABA with less smoking history maintain their pulmonary function by medical therapy.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 proposed a COPD assessment framework focussed on symptoms and on exacerbation risk. This study will be conducted in Japanese subjects with moderate-to-severe COPD and with an mMRC score of 1 or greater. It will assess whether the GOLD 2011 strategy is effective in medical practice in a real world setting in Japan. The purpose of this study is to assess the control of COPD using a symptom and exacerbation risk treatment strategy based on GOLD 2011. This abstract summarizes the methodology of the study, in advance of the publication of the results. Methods This study is a 24-week, multicentre, randomised, double-blind, double-dummy, parallel group trial. 400 patients will be recruited and randomised to receive treatment with either salmeterol/fluticasone propionate (SFC) 50/250 mcg twice daily or tiotropium bromide 18 mcg once daily. COPD management of patients will be assessed at 4-weekly intervals and if patients remain with high levels of symptomatic impact on their daily health life, as measured by the CAT score, or experience an exacerbation, they have the option, after discussion between doctor and patient, to step up to treatment with both medications, i.e. SFC and tiotropium (TRIPLE therapy). The primary endpoint is the number of patients who are able to remain on the randomised therapy. Patients still not well controlled on TRIPLE have the option to add further treatments. The possibility of step-down from TRIPLE based on lack of response is also incorporated. The results of this study will help physicians to understand when TRIPLE therapy is more effective for management of symptoms and exacerbations in patients with moderate to severe COPD. This study will also clarify what proportion and what type of patients can be managed on single therapy and which on TRIPLE therapy. Background The pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) patients is intended to improve the lung functions, exercise functions, and activities of daily living (ADL). When we produce the pulmonary rehabilitation program, it is necessary to know their life style in detail. However, there are few reports about the lifestyle of them. Methods Thirty-nine severe COPD patients (66.1 ± 6.9 years old) were participated in this study, and divided them into two groups (Group A and Group B). Group A consisted of 23 patients (Severe COPD; Stage III), and Group B consisted of 16 patients (Very Severe COPD; Stage IV). We investigated their lung functions, nourishment states, exercise functions, ADL level and life style. We performed informed consent to all the members when investigating it. Results Lung functions and exercise functions of B group were significantly lower than those of A group. The ADL level in both groups was lower, especially in B group. They had few daily roles at home and seldom participated in community activities. And many of them had various anxieties about their daily activities and social participation such as "going out", "trip". Conclusion To improve the QOL of sever COPD patients, it is necessary to improve not only basic ADL but also other daily and social activities. Background and Aim of Study Airflow limitation may be common among patients who need thoracic surgery and may influence perioperative status and postoperative outcomes. The objectives of our study were to investigate the prevalence of airflow limitation among patients who had thoracic surgery in our hospital and to analyze its impact on postoperative complications and outcomes after surgery. Methods We retrospectively reviewed clinical records of patients who underwent thoracic surgery in Juntendo University Hospital from 1996 to 2013. The patients who lacked data of pulmonary function before surgery were excluded. Patients were classified into two group, Group A who had airflow limitation (FEV1/FVC < 70%) before surgery and Group B without airflow limitation, and analyzed the prevalence of comorbidities, frequency of postoperative complications. Results Of 4676 patients who underwent thoracic surgery, 3667 cases who has preoperative pulmonary function data were analyzed. The mean age was 61.2 ± 13.8 years old, 59.6% was male, and 51.5% was current or ex-smoker. Comorbidies that were more prevalent in Group A included hypertension, diabetes mellitus, cardiovascular diseases, COPD, bronchial asthma, neurological diseases and collagen vascular diseases (P < 0.01) while no significant difference in prevalence was noted in hyperlipidemia and interstitial lung diseases. Postoperative complications including respiratory failure requiring oxygen supplementation, atelectasis, delirium, re-operation, arrhythmia, and prolonged air leakage were significantly prevalent in Group A (P < 0.01) The period of postoperative hospital stay showed no significant difference between Group A and B. Conclusion Patients with airflow limitation had more comorbidity and postoperative complications after thoracic surgery than those without airflow limitation.

Background Inflammatory cells and mediators may lead to destructive changes in airways and lung hyperinflation in sever chronic obstructive pulmonary disease (COPD). Aims To tested the hypothesis that neutrophils in venous blood have a relationship with the ratio of forced expiratory to forced inspiratory volumes for the first 0.5 second (FEV0.5/FIV0.5) as a measure of hyperinflation in sever COPD. Methods Five male outpatients with COPD (83 ± 4 age, forced expiratory volume in 1 second (FEV1) 39.1 ± 7 % predicted), all ex-smokers and undergoing long-term oxygen therapy, were included. Measurements were obtained more than four times for the ratio of circulating neutrophil count to peripheral white blood cell count (neutrophil %), FEV1, FEV1%predicted, C-reactive protein (CRP) and FEV0.5/FIV0.5 from July 1, 2011, to July 31, 2012. Results Neutrophil%(69.9 ± 10.8 %) was significantly correlated with FEV0.5/FIV0.5 (0.79 ± 1.23) (rs = −0.56579, p < 0.01), FEV1(0.67 ± 0.11 L)(rs = 0.572239, p < 0.05), and FEV1% predicted (41.15 ± 8.06 %)(rs = 0.540248, p < 0.05). CRP(0.36 ± 0.44 mg/dl) was not significantly correlated with FEV0.5/FIV0.5. Conclusion This report suggests that circulating chronically increasing Neutrophil% might be able to progress the lung hyperinflation in sever COPD. NAOKI IJIRI, YOSHIHIRO TOCHINO, KAZUHIRO YAMADA,  NAOKO YOSHII, GAKUYA TAMAGAKI, FUMIHIRO NAGAYASU,  KAZUHIRO ASAI, HIROSHI KAMOI, Methods We studied patients with COPD in our hospital between August 2008 and July 2011. They were classified to 4 groups in accordance with the GOLD2011. We compared CAT scores with clinical indicators of six minute walk test (6MWT) and pulmonary function test (PFT) between group A (mild, low CAT scores) versus B (mild, high CAT scores), C (severe, low CAT scores) versus D (severe, high CAT scores) and A+C (low CAT groups) versus B+D (high CAT groups). Clinical indicators of 6MWT included six minute walk distance (6MD) and desaturation area (DA), and PFT included %DLCO, maximal mid-expiratory flow (MMF) and δN2.

The 60 COPD patients were examined. They were 72.9 ± 7.5 years old and 86.7% were male. 19(32%) were classified as GOLD 2011 group A, 6(10%) group B, 15(25%) group C, 20(33%) group D. 6MD and %DLCO in Group D was significantly lower than in group C. 6MD, %DLCO and MMF in Group B+D was significantly lower than in group A+C. DA and δN2 of Group D and B+D was higher than that of group C and A+C, respectively. There were no differences in all clinical indicators between group A and B. Conclusion Our results suggested that exercise intolerance, desaturation on exertion and small airway obstruction might correlate with high CAT scores in COPD patients with low pulmonary function.

KATSUYA ONISHI 1 , DAISUKE YOSHIMOTO 2 , GERRY HAGAN 2 , PAUL W JONES 3 1 Onisi Heart Clinic, Mie, Japan, 2 Medical Affairs Respiratory, GlaxoSmithKline K.K., Tokyo, Japan, 3 

Background and Aim of Study Although cardiovascular disease and chronic obstructive pulmonary disease (COPD) share common risk factors and COPD patients frequently have comorbid cardiovascular diseases, the prevalence of COPD in outpatients with cardiovascular diseases in Japan is unknown. Methods In a multi-center, non-interventional, prospective study conducted at 17 centers across Japan, we investigated the prevalence of airflow limitation compatible with COPD (defined as FEV1/FEV6 < 0.73 by hand-held spirometry, Hai-checker) in outpatients routinely visiting for their cardiovascular diseases and who were aged 40 years or older with a smoking history. Each subject completed the COPD Assessment Test (CAT) prior to hand-held spirometer testing. Results A total of 1,001 subjects participated and the spirometry data of 995 subjects were available. 95.5% of subjects were male and age was 66.6 ± 10.0 (mean ± SD) years old. The prevalence of airflow limitation compatible with COPD was 27.0% (n = 269), and 87.7% of these subjects (n = 236) have not been diagnosed as COPD before. In subjects with CAT score >10, the prevalence of airflow limitation was 36.5%, and higher than in subjects with score < 10, it was 23.4%; sensitivity was 0.37 and specificity was 0.76. Conclusion The prevalence of airflow limitation in this study indicates that a quarter of outpatients with cardiovascular diseases have COPD, although almost all of them are undiagnosed. This suggests that it is important to look routinely for COPD in cardiovascular disease outpatients. Use of the CAT in cardiology clinics in patients over 40 years old with smoking history may be a simple way for assessing patients who need to have spirometry to diagnose COPD. Aim The study evaluated the clinical benefit of once daily long-acting β2 agonist indacaterol add-on therapy in the stable COPD patients with muscarinic antagonist tiotropium treatment. Methods Japanese 18 patients(17 male/1 female, mean age72 ± 7.2, severity stageII 8/stageIII 10) with COPD, treated with tiotropium 18 μg more than 3 months and had some COPD symptoms, were added indacaterol 150 μg once daily. Respiratory function, IOS, CAT, 6MWD and the questionnaire of usability Breeze Heller were assessed before and after 8 weeks add-on therapy. Results Three question of CAT (Activity, breathlessness, Confidence), 6MWD, IC,% V25 has improved significantly on 8 weeks after add-on therapy. The other three question of CAT (Chest tightness, sleep, energy), FEV1, FVC, IOS (R5, R20, R5-R20, X5, AX, Fres) was no significant difference, but some subjects showed a significant improvement. The questionnaire survey of usability Breeze Heller showed that it is easy to use. Conclusion This result suggest that respiratory function, air trapping, symptoms, QOL, physical activity and exercise tolerance are improved by combining different mechanisms bronchodilators with LAMA blocking the M3 receptor and LABA to stimulate the β 2 receptor. Background The CAT is an eight-item questionnaire designed to assess and quantify the impact of COPD symptoms on health status and is widely used in many countries. The nutritional impairment is an important systemic manifestation associated with poor prognosis and deteriorated quality of life. However, a relationship between nutritional status and the CAT scores is unknown. Aim To determine the relationship between the CAT score and nutritional status assessed by MNA-SF and compare the ability of CAT to predict exacerbation with that of MNA-SF. Methods Pulmonary function, modified MRC scale (mMRC) and body mass index (BMI) were evaluated in 60 stable patients with COPD (mean age:72 yr, mean %FEV 1:61.4%). The CAT and MNA-SF were also completed. After initial assessment, exacerbations were recorded prospectively for one year. Results The mean CAT score was 14.4 ± 7.5 (low impact:37%, medium impact:38%, high impact:20%, very high impact:5%). The mean MNA-SF score was 11.4 ± 2.4 (well nourished:51%, at risk:37%, malnourished:12%). The CAT scores were significantly correlated with mMRC and %FEV 1, but not correlated with BMI and MNA-SF scores. The MNA-SF score was correlated with exacerbation frequency, whereas the CAT score was not associated with exacerbations frequency.

Conclusion The CAT appears to assess health status of COPD independently of nutritional status. MNA-SF as well as CAT is of clinical importance because it can predict COPD exacerbation. Background and Aim Nutritional state is an important determinant of symptoms, disability, and prognosis in chronic obstructive pulmonary disease (COPD). Anxiety and depression are the major comorbidities in COPD. The Mini Nutritional Assessment® (MNA) questionnaire is a simple, validated questionnaire widely used to identify the elderly at risk for malnutrition; the MNA explores 4 components that affect malnutrition. We examined whether impaired nutritional status using the MNA is associated with anxiety and depression in COPD. Methods A total of 105 clinically stable COPD patients (mean age, 73.7 years; Global Initiative for Chronic Obstructive Lung Disease stage I:18, II: 43, III: 39, IV: 5; male, 97), who were previously investigated in the association study between malnutrition assessed by the MNA and decreased exercise intolerance (presented in ATS 2013), were included in the study. Pulmonary function, exercise intolerance (6-minute walking distance test), anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), and nutritional status (MNA) in addition to body composition were evaluated. We calculated the total score and scores for each of the 4 nutritional status domains from the MNA: anthropometric, functional, dietary and self-perception assessment. Results Both depression and anxiety scores of the HADS were significantly correlated with the MNA total score (high scores indicates good nutritional status) (p = 0.001, and 0.018, respectively) (rho = −0.312, and −0.231, respectively). The depression score was also significantly correlated with the MNA self-perception score (p < 0.001, rho = −0.394). Conclusions The malnutrition assessed by the MNA was associated with depression and anxiety in patients with COPD. Especially, depression was associated with self-perception affecting malnutrition in COPD. Treating depression may improve nutritional status in COPD patients. Background Although smoking is the strongest risk factor of COPD development, some patients have no history of smoking. Nonsmoker COPDs will present another characteristics and risk factors, compared with smoker COPDs. Methods Dominant characteristics in never-smoker COPD compared to ever-smoker COPD using the data of 4th Korean National Health and Nutrition Examination Survey (KNHANES) 2007-2009 were evaluated. COPD was defined as FEV1/FVC < 0.7. Patients of known asthma or patients with restrictive lung function (FEV1 < 80% and FEV1/FVC > 0.7) were excluded. Neversmoker was defined as subject who had never smoked or had smoked in past less than 5 pack-years. Results Among total 9,152 subjects who were enrolled during that period and performed pulmonary function test (PFT), 6,934 subjects showed acceptable PFT. Since exclusion criteria, finally 5,784 subjects were evaluated. The proportion of smokers was 60% and incidence of COPD was 14.3%. The prevalence of COPD in ever-smokers was much higher than in never-smokers (24.6% vs. 7.4%, p < 0.0001). History of tuberculosis (never-smokers: OR 2.42, CI 1.48-3.96 vs. ever-smokers: OR 1.85, CI 1.29-2.65) and presence of bronchiectasis (never-smokers: OR 9.05, CI 3.17-25.83 vs. ever-smokers: OR 2.58, CI 0.72-9.19) were more closely related with the existence of COPD in never-smokers, compared to ever-smokers. Besides those risk factors, age, educational levels, living with partner, and family income were also significant risk factors of COPD in both groups. Conclusions When nonsmokers of no known asthma present PFT of obstructive pattern, history of tuberculosis or presence of bronchiectasis should be considered. Objective To contrasted the effects between An' ningpai and its main component eucalyptol in chronic cigarette smoke-exposed rats, further explored its mechanism on airway MCC function. Methods The models were established by continuously exposeing cigarette smoke for 12 weeks. An' ningpai and eucalyptol, intervened at the beginning of smoke exposed, were compared with after intervention treatment between different groups on rats general morphology, airway bacterial load, airway scavenging activity on exogenous H. influenzae, microstructure change under TEM, AB-PAS staining, airway mucin MUC5AC production and expression. Results Compared with smoke exposed group, the pathological structure was relatively improved in An' ningpai intervention group, though obvious structural changes still exited compared with normal control group. Bacterial load was reduced in the rat airway of An' ningpai intervention group, and scavenging activity on exogenous H. influenzae was accelerated. TEM results showed airway epithelial cilia structure was relatively intact, that prompted medical intervention for cilia played a protective role. But for the damage of the cell structures and organelles the improvement was not obvious. The effect of An' ningpai on mucous secretion was manifested in regulating acid mucopolysaccharide proportion secreted by airway epithelium goblet cells, affecting the properties of mucus, and reducing airway MUC5AC expression level. The therapeutic effect of eucalyptol intervention group was similar to that of An' ningpai intervention group, no significant statistical difference showed. Glycerol as a drug control had no influence to the detection indexes. Conclusions An' ningpai has the effects on reducing airway bacterial load in rats exposed to cigarette smoke, increasing bactiria scavenging activity by improving airway mucociliary clearance function. The effects are mainly performed by protecting airway epithelial cilia structure, regulating acid mucopolysaccharide ratio and mucin MUC5AC level secreted in goblet cells. Key Words An' ningpai; Eucalyptol; COPD; Rats exposed to cigarette smoke; Mucociliary clearance; H. influenzae.

Rationale Although the textbook tells that expiratory airflow limitation in emphysema occurs at the peripheral airways and that wheezes are generated there, wheezes are often heard without stethoscope. Are they really generated periphery in the lung? We have recently revealed with 4D-CT images that expiratory airflow limitation in emphysema occurs at the intra-mediastinal airway (intra-thoracic trachea, main bronchi, right lobar bronchi) due to its dynamic compression enhanced by the surrounding overinflated lungs, because the membranous part there has no cartilage and highly deformable. We performed expiratory airflow simulation by the use of computational fluid dynamics (CFD), and investigated the relationship between the tracheal shape and the pressure fluctuation generated by the airflow. Methods A 4D finite element model in which all nodes are displaced according to breathing motion was constructed. A cylindrical trachea opens to the atmosphere at the position of the subglottic cavity. The posterior wall of the trachea was deformed mimicking the 4D-CT images Airflow during expiration was computed by solving numerically incompressible Navier-Stokes' equation under moving boundary condition (solver: AcuSolve, Altair Engineerng, USA). Time step was assigned at 0.0001 sec, and dynamic LES (large eddy simulation) model was applied for turbulence. Results Only slight pressure fluctuation beyond 1,000 Hz caused by turbulence was observed in the airflow simulations in the non-deformed trachea. However, in the deformed trachea, periodical vortex releases with 300-900 Hz at the end of protrusion of the membranous part was found with the range of flow rate between 0.5 L/s and 3.0 L/s. Airflow simulation through the peripheral airway was performed using the same model with the scale of 1/10, and no apparent pressure fluctuations were observed within the airway. Conclusions The present simulation study strongly has suggested that wheezes are generated not at the peripheral but at the intra-mediastinal airway.

MASUO NAKAMURA 1 , HIROO WADA 1 , KOJIRO HONDA 1 , KEITARO NAKAMOTO 1 , HARUYUKI ISHII 1 , SHINICHI INOUE 2 , FUMIE KOBAYASHI 2 , HIROSHI KAMMA 3 , HAJIME TAKIZAWA 1 , HAJIME GOTO 1 1 Departments of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan, 2 Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan, 3 

Background Even short-term exposure to cigarette smoke causes airway inflammatory response, which were similar to characteristic neutrophilic inflammation seen in COPD or steroid-resistant asthma. IL-17 is a pro-inflammatory cytokine, provoking neutrophilic inflammation. The role of IL-17 on airway inflammation induced by cigarette smoke was investigated, using the murine model. Methods Both IL-17 deficient mice and wild-type mice were exposed to tobacco smoke for 5, 8, 12 and 26 days, using the tobacco smoke exposure system. Mice were anaesthetized and sacrificed, and then bronchoalveolar lavage (BAL) fluid was collected, prior to obtaining lung tissues. Cellular responses in BAL fluid were determined. Protein levels of pro-inflammatory proteins in BAL fluid were measured using enzyme-linked immunosorbent assay, as well as mRNA levels in the lung tissues using quantitative RT-PCR. Sections of 3 mu m of paraffin-embedded lung tissue were stained with hematoxylin and eosin. Result The number of neutrophils in BAL fluid reached the maximum on the 8th day, and then it was decreased on the 26th. The number of neutrophils in BAL fluid, and mRNA levels of KC, GM-CSF, and MMP-9 in lung tissue were lower in IL-17 deficient mice than those in wild-type mice (p < 0.05). No significant difference in mRNA levels of tumor necrosis factor-alpha was detected. These results indicated that IL-17 play a role in neutrophilic inflammation induced by cigarette smoke, probably via KC, GM-CSF and MMP-9. Conclusion Using murine model, we demonstrated that IL-17 plays a role in the induction of neutorphilic inflammation evoked by cigarette smoke exposure.

AMIRA P. TARIGAN 1 , TAMSIL SYAFIUDDIN 1 , FAISAL YUNUS 2 , SURADI -3 , YAHWARDIAH SIREGAR 1 , SYAFRUDDIN -4 1 Pulmonology Departement, University of North Sumatera, Medan, Indonesia, 2 Departement Pulmonology, University of Indonesia, Depok, Indonesia, 3 Departement Pulmonology, University of Surakarta, Surakarta, Indonesia, 4 Eijkman Instituut, Jakarta, Indonesia Background Chronic Obstructive Pulmonary Disease (COPD) will be the highest cause of mortality and morbidity in the world. Data showed that 85-90% of COPD cases are caused by smoking, but only 15-20% of chronic heavy smokers who will develop COPD. This indicates a different susceptibility to damage from smoking that may be linked to genetic factors. The purpose of this study was to analyze the occurrence of Chronic Obstructive Pulmonary Disease role path of -308G/A, -238G/A TNFalpha gene polymorphism and +252A/G LTalpha gene polymorphism in smokers. Method Case-control study, comparing the genetic group of people who have COPD (cases) and a group of people who do not suffer from COPD (control) with the same smoking history. Implementation of the study started Background and Aim of Study Efferocytosis, homeostatic phagocytosis of apoptotic cells, prevents the release of toxic intracellular contents and subsequent tissue damage. Impairment of efferocytosis was reported in alveolar macrophages (AMs) of patients with chronic obstructive pulmonary disease (COPD), a common disease caused by smoking. In COPD, histone deacetylase (HDAC) activity is reduced in AMs. We investigated whether the reduction of HDAC activity is associated with the impairment of efferocytosis. Methods Murine AMs were collected by bronchoalveolar lavage. Pretreatment of AMs with cigarette smoke extract (CSE) or trichostatin A (TSA) and their ability of efferocytosis for apoptotic human polymorphonuclear leucocytes was assessed. RhoA or Rac activity was evaluated by enzyme-linked immunosorbent assay and colorimetric approaches. Surface expressions on AMs were analyzed by flow cytometry. Results CSE or TSA reduced HDAC activity and suppressed efferocytosis. TSA inhibited the activity of Rac, a key mediator of efferocytosis. These TSA-induced impairments were restored by treatment of AMs with aminophylline, a potent activator of HDAC. To further elucidate the underlying mechanism, we explored a role of CD9 in TSA-induced impairment of efferocytosis. CD9 is a tetraspan transmembrane protein, that facilitates the uptake of several pathogens and materials. TSA profoundly down-regulated the expression of CD9 on AMs. The expression of CD9 was partly down-regulated by Rac inhibitor. Finally, pretreatment of anti-CD9 mAbs inhibited efferocytosis, which was attributable to the reduced binding of AMs to apoptotic cells. Conclusion Cigarette smoking impairs efferocytosis via inhibition of HDAC/ Rac/CD9 pathways. Aminophylline/theophylline is effective for restoring the impairment of efferocytosis and might have benefit for the treatment of patients with COPD.

Backgrounds and Aim of Study That obstructive sleep apnea (OSA) occurs at a lower body mass index (BMI) in Asian population compared to those of European descent is well known. However, characteristics of Asian patients with obesity hypoventilation syndrome (OHS) have not yet been established. We aimed to reveal the prevalence of OHS and characteristics of individuals with OHS in Japan, which clarified the factors related to hypercapnia in OHS patients. Methods We studied 983 consecutive patients hospitalized for examination of OSA from October 2008 to September 2012. Multiple regression analysis was performed to identify variables independently associated with arterial carbon dioxide pressure (PaCO2) in the 162 obese OSA (BMI > 30 kg/m 2 and apnea-hypopnea index (AHI) > 5/h). Results The prevalence of OHS in OSA and that in obese OSA were 2.3% and 12.3%, respectively. In addition to increased PaCO2 and AHI, patients with OHS had a lower expiratory residual volume even after adjustment for waist circumference. Multiple regression analysis revealed that independent of age and BMI, arterial oxygen pressure (PaO2) (contribution rate (R 2 ) = 7.7%), 4% oxygen desaturation index (ODI) (R 2 = 8.9%), %carbon monoxide diffusing capacity/alveolar volume (%DLco/VA) (R 2 = 8.3%), and hemoglobin concentration (R 2 = 4.9%) as well as waist circumference (R 2 = 4.9%) were independently associated with PaCO2. With long-term continuous positive airway pressure (CPAP) treatment (12.3 ± 4.6 months), the PaCO2 levels in 12 of the 14 patients with OHS improved. Conclusions The prevalence of OHS in obese OSA in Japan was approximately the same as in the West, even at less obesity (BMI 36.7 ± 4.9 kg/m 2 ). Factors contributing to the elevation of %DLco/VA (hemoglobin concentration, cardiac output, etc.) should be considered in the management of OHS. And the long-term CPAP treatment was effective to attain PaCO2 < 45 mmHg in OHS patients. Background and Objectives Obstructive sleep apnea (OSA) affects our daily functional and cognitive performance. Continuous Positive Airway pressure (CPAP) treatment may improve our symptoms and quality of life to different extents. This study investigated the relationships between CPAP adherence and daytime sleepiness, quality of life, emotion, and adherencerelated cognition in subjects with OSA, after 1 year of CPAP use. Methods Subjects who were newly diagnosed of OSA and CPAP therapy navie were recruited. Epworth sleepiness scale (ESS), Calgary sleep apnea quality of life index (SAQLI), Depression anxiety stress scale (DASS21), and Self-efficacy measure for sleep apnea questionnaire (SEMSA), were assessed before and after 1 year of CPAP treatment. CPAP usage data were downloaded at the completion of this 1-year study. Regression analyses were performed to assess the dose-response relationship between CPAP adherence and daily performance in subjects with OSA. Results 100 subjects with OSA indicated for CPAP treatment were recruited, with an average age of 52 ± 10 years, BMI of 29.0 ± 5.5 kg/m 2 , and AHI of 36.2 ± 22 events/hour. After one year of CPAP treatment, average CPAP daily usage was 3.5 ± 2.7 hours per day and usage index (the percentage of days using CPAP for at least 4 hours per day) was 48% ± 38%. And, the CPAP usage index was found to have dose-response effects on the improvement of Conclusions After 1-year CPAP treatment, the CPAP adherence was shown significant dose-related improvements in the functional and cognitive performance in subjects with OSA. Background and Aim of Study Patients with sleep apnea syndrome (SAS) and patients with diabetes mellitus (DM) are increasing in Japan. We sought to assess the recent prevalence of DM and the glucose tolerance profile of patients with SAS. Methods Data from 103 patients with SAS (apnea-hypopnea index > 5 events/hr; male 76, female 27; mean age 53.8, mean body mass index 28.6) were reviewed. A 75 gm oral glucose tolerance test (OGTT) was performed in SAS patients who had not been diagnosed with DM. Homeostasis model assessment insulin resistance index (HOMA-R) and insulinogenic index (II) were calculated. We adopted the diagnostic criteria of the Japan Diabetic Society and the American Diabetes Association. Results 24 SAS patients (23.3%) had already been diagnosed with DM. 7 SAS patients (6.8%) were diagnosed with diabetes at the time of the current OGTT. 24 SAS patients (23.3%) were diagnosed with impaired glucose tolerance and/or impaired fasting glucose. 48 SAS patients (46.6%) were normal on OGTT, but 13 were found to have a one-hour serum glucose level higher than 180 mg/dl. Abnormal HOMA-R and abnormal II were found in 51.9% and 24.7% of subjects, respectively. Conclusion 30.1% of SAS patients had DM and only 17.5% of SAS patients had intact glucose tolerance. Background and Objective Sleep disturbances in patients with chronic obstructive pulmonary disease (COPD) such as poor sleep quality, nocturnal oxygen desaturation, and the presence of coexistent obstructive sleep apnea (OSA), which is called overlap syndrome, have been described in several reports. However, in the majority of previous reports, sleep was assessed by polysomnography or subjective reports. This is the first population-based study that assessed sleep quality and hygiene in COPD patients using an actigraphy and type 3 portable monitoring in a home environment. This study aimed to determine the prevalence of COPD patients and patients with overlap syndrome in urban Asian male subjects by actigraphy and type 3 portable monitoring at home. Methods A cross-sectional epidemiological health survey of 303 male employees (age 43.9 ± 8.2 y; body mass index 24.0 ± 3.1 kg/m 2 : mean ± SD) was done. Sleep quality was measured by the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). A Respiratory Disturbance Index (RDI) of 5 and over indicated OSA. Results Nineteen subjects (6.3%) had COPD and 181 (59.7%) had OSA. Eleven (3.6%) had overlap syndrome. Sleep duration, ESS, and PSQI scores were not significantly different between COPD patients and normal control subjects. However, COPD patients had significantly longer sleep latency (P = 0.019), lower sleep efficiency (P = 0.017), and a higher sleep fragmentation index (P = 0.041) and average activity (P = 0.0097) during sleep than control subjects. They also had a significantly higher RDI and more severe desaturation during sleep than control subjects (P < 0.01). The difference remained after adjustment for age and BMI, but disappeared following adjustment for RDI. Conclusions From population-based data collected by actigraphy and type 3 portable monitor in the home environment, even patients with mild-tomoderate COPD had nocturnal desaturation and OSA-related impaired sleep quality although the ESS or PSQI revealed no significant symptoms.

NAOKI OKAMOTO 1 , TSUNETO AKASHIBA 1,2 , AKIHITO UEMATSU 1 , KENICHI NAGAOKA 1 , KOUMEI IGEI 1 , YU KOHZU 1 , NATSUKO KIYOFUZI 2 , KAZUHITO KATSURA 1 , SYU HASHIMOTO 1 1 Department of Respiratory Medicine, Nihon University Scholl of Medicine, 2 Department of Sleep Medicine, Nihon University School of Medicine, Japan Background and Aim Nasal CPAP (nCPAP) has been a first-line treatment for patients with OSAS. Although nCPAP can completely abolish upper airway occlusion and apnea during sleep, substantial high pressure affects pulmonary systems of patients and may be harmful in long-term duration. However, long-term effects of nCPAP on pulmonary functions and arterial blood gases are still unclear. Therefore, we investigate the changes of pulmonary functions before and after nCPAP treatment on long-term duration in patients with OSAS. Method Seventy-five male patients with OSAS who underwent nCPAP therapy more than 5 years were included in this study. Pulmonary function test and blood gas analysis were performed before and after 7 and 14 years after treatment. Pulmonary function tests consisted of spirometry, pulmonary volumes, diffusion capacity and flow-volume curve. Subjects were divided in two groups, high pressure group (nCPAP > 10 cmH2O) and low pressure group (nCPAP < 10 cmH2O) and the changes of pulmonary functions were compared between two groups. Results There were no significant changes on pulmonary functions (%VC, FEV1.0%, %FEV1.0, %TLC, %FRC, %RV, and %DLco) and arterial blood gases (PaO2, PaCO2, and pH). before and after 7 years and 14 years of nCPAP treatment. There were no significant changes of pulmonary functions and blood gases between low pressure groups and high pressure groups. Conclusion Long-term nCPAP treatment did not affect on pulmonary functions and arterial blood gases in patients with OSAS, even in patients with high pressure (>10 cmH2O). nCPAP is safe treatment for patients with OSAS in long-term duration. Background and Aim of Study Obstructive sleep apnea syndrome (OSAS) patients concomitant with chronic obstructive pulmonary disease (COPD), termed as overlap syndrome (OS), have a worse prognosis than patients with only one of these diseases. The aim of this study is to investigate alterations of systemic inflammatory mediators in patients with OSAS, COPD, and OS and to explore relations between serum levels of inflammatory mediators and polysomnography (PSG) variables, pulmonary function variables, and scores of health status questionnaires in OS patients. Methods This prospectively observational study was implemented from March, 2012 to May, 2013 and designed with three groups as follows: COPD group included patients with naïve COPD alone; OSAS group included patients with moderate-to-severe OSAS alone; OS group included patients with OSAS and naïve COPD. Venous blood samples were obtained in the morning of PSG. Results A total of 46 patients (13 OSAS patients, 13 COPD patients and 20 OS patients) were enrolled. High-sensitive C-reactive protein (hs-CRP) was elevated in OS patients as compared with OSAS patients and COPD patients (p = 0.027 and p = 0.013, respectively). Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were elevated in OS patients as compared with OSAS patients. Hs-CRP, TNF-α and IL-6 were similar between OSAS patients and COPD patients. Interleukin-8 (IL-8) was similar among three groups. In OS patients, IL-6 and IL-8 were negatively correlated with first second of forced expiratory volume/forced vital capacity(FEV1/FVC) and total lung capacity(TLC), respectively (r = −0.48, p < 0.05; r = −0.83, p < 0.001, respectively). The tested inflammatory mediators showed no correlation with PSG variables (Apnea-hypopnea index, lowest SaO2, and mean SaO2) and scores of health status questionnaires (COPD assessment test and modified Medical Research Council Dyspnea Scale). Conclusion As compared with OSAS patients and COPD patients, OS patients had significantly higher systemic inflammatory mediators and were negatively correlated with FEV1/FVC and TLC.

Introduction In 2009, we demonstrated that acceptance rate of Continuous Positive Airway Pressure (CPAP) treatment in patients diagnosed with Obstructive Sleep Apnoea (OSA) was significantly higher with an additional 15-minute individual consultation after the "usual" structured educational talk than those having the talk alone. Objective A Specialist Nurse-Clinic follow-up would be offered to all patients who agreed to receive CPAP therapy, where the use and compliance of CPAP treatment would be monitored and evaluated. Methodology It's a retrospective study to evaluate 1-year CPAP compliance rate in 2011 after CPAP therapy from both medical and nursing consultation notes. Patients were all scheduled to the clinic one-month after initiation of CPAP therapy. Respiratory nurses would deal with problems associated with machine, accessories or interface. Data reading including average usage hours, mask leakage, residual Apnoea-Hypnoea-Index was recorded. Advices were frequently offered to enhance comfort and adherence. Overnight oximetry reports would be reviewed. Phone follow-up would be offered if necessary. Results 90% of 259 patients attended the educational talk and 15-minute individual consultation. Although 77.4% patients initially agreed for CPAP therapy, only 140 patients attended the nurse clinic and the rest attended physician clinics. 84 patients (60%) reported problems related to CPAP during follow-up, of which 86% were eventually solved. Acceptable compliance was defined by Kribbs et al. as CPAP use at least 4 h/day for at least 70% of the nights per week. The CPAP compliance rates were significantly higher for patients attending specialist nurse-clinic (86.4%) than those who did not (52.1%) (physician follow-up only). (p < 0.001). Conclusion A Specialty Nurse Clinic on CPAP therapy can improve patient compliance with CPAP therapy.

Background Panic disorder (PD) is a complex condition that is further complicated by its numerous inducers, which include hypercapnia, hypoxia, sodium lactate, caffeine and cholecystokinin. It seems unlikely that there are specific suffocation receptors for each of these inducers in the brain. Novel hypothesis for the cause of panic disorder should be submitted without the brain. Methods The pulmonary neuroepithelial bodies (NEBs), which are situated at the bifurcation point of the small bronchi, act as storage cells for 5-hydroxytryptamine (5-HT) and sensors for suffocation. If we suppose that PD might represent hyperfunction of inflammatory NEBs, bradykinin (BK) which augments the airway hyper-response to diverse indcers might cause these cells to release 5-HT along with peptides and panneuroendcrine markers from their dence-core secretory granules. It was revealed that BK with 5-HT could cross the blood-brain barrier (BBB). Results When 5-HT released from these cells along with BK cross the BBB, the release of 5-HT at the axonal terminals in the serotonergic neurons in the brain will be inhibited by the 5-HT1A autoreceptor. The inhibition of 5-HT at the axonal terminal causes to suppress the periaqueductal gray matter, which inhibits flight reactions to impending danger, pain or asphyxia. In short, this serotonergic situation might bring about PD. Conclusion According to this theory, the type of inducer that the PD patient is exposed to is unimportant as long as it stimulates the NEBs, and through the effect of 5-HT and BK, PD would be revaluated as a lung disease that directly and reversibly affects the brain. Background and Aim of Study Previous studies have shown a high prevalence of obstructive sleep apnea (OSA) among patients with Alzheimer's disease (AD). However, it is poorly assessed whether chronic intermittent hypoxia (CIH), which is a characteristic of OSA, affects the pathophysiology of AD. We aimed to investigate the direct effect of intermittent hypoxia (IH) in pathophysiology of AD in vivo and in vitro. Methods In vivo, 15 male triple transgenic AD mice were exposed to either CIH or normoxia (5% O2 and 21% O2 every 10 min, 8 h/day for 4 weeks). The amyloid-beta (Abeta) profile, cognitive brain function and brain pathology were evaluated. In vitro, human neuroblastoma SH-SY5Y cells stably expressing wild-type amyloid beta precursor protein were exposed to either IH (8 cycles of 1% O2 for 10 minutes followed by 21% O2 for 20 minutes) or normoxia. The Abeta profile in the conditioned medium was analyzed. Results CIH significantly increased levels of Abeta42 but not Abeta40 in the brains of mice without the increase in hypoxia-inducible factor 1, alpha subunit (HIF-1alpha) expression. Furthermore, CIH significantly increased intracellular Abeta in the brain cortex. There were no significant changes in cognitive function. IH significantly increased levels of Abeta42 in the medium of SH-SY5Y cells without the increase in the HIF-1alpha expression. CIH directly and selectively increased levels of Abeta42 in the AD model. Conclusion Our results suggest that OSA would aggravate AD. Early detection and intervention of OSA in AD may help to alleviate the progression of the disease.

Background and Aim Non-Invasive Mechanical Ventilation is a modality that gives ventilatory support without bypassing the upper airway with the use of devices such as tracheal tube, laryngeal mask or tracheostomy. This paper aims to describe the practice of instituting NIMV in UST Hospital. It will review the outcomes as well as the appropriateness of use and adherence to the guidelines in this institution. Methods We reviewed the charts of all inpatients placed on non-invasive mechanical ventilation from July 2011 to March 2013 with emphasis on the following variables: demographic and clinical profile, clinical course and outcome. Patients from the pediatric age group and patients placed on CPAP for management of Obstructive Sleep Apnea were excluded. Results A total of 76 patients were included in the study. There were 35 patients (46%) who failed NIMV. Out of this, 12(34%) were intubated but were eventually discharged, 10(28%) were intubated and subsequently died, and 13(37%) died while on NIMV. The most common indication for instituting NIMV was pneumonia. The success rate was 53.9%. Success was highest among patients placed on NIMV because of cardiac causes, asthma and metabolic acidosis. Conclusion The failure rate of NIMV in our institution is high compared with previous studies even if we exclude those patients placed on NIMV because of advance directives. Many of those who failed NIMV died, therefore, the importance of patient selection is emphasized. Aside from patient selection, standard of care should be taken into consideration. Its impact in the outcome should be investigated in future studies. Anti-ARS antibodies were detected in 8 patients (25%) (anti-Jo-1 in 1 patient, anti-PL-7 in 1 patient, anti-PL-12 in 2 patients, anti-EJ in 3 patients and anti-KS in 1 patient). Five patients (62.5%) in the anti-ARS-antibodiespositive group showed erythema suggestive of myositis such as a mechanic's hand, periungual erythema and nail fold bleeding; on the other hand, no patients in the anti-ARS-antibodies-negative group showed erythema suggestive of myositis. As to radiological findings on high-resolution CT, the anti-ARS-antibodies-positive group showed a significantly higher rate of cystic formations, while the anti-ARS-antibodies-negative group showed significantly higher rates of consolidations and thickening of bronchovascular bundles. The anti-ARS-antibodies-positive group had significantly shorter duration from diagnosis to the beginning of treatment than the negative group, although there were no significant differences in resistance to treatment and survival between the 2 groups. There were also no significant differences in bronchoalveolar lavage fluid and results of pulmonary function tests. Conclusions We detected anti-ARS antibodies in 25% of SS patients. This investigation suggests that anti-ARS antibodies modify the clinical features of SS. Therefore, we should measure anti-ARS antibodies in patients diagnosed with SS.

MASARU ANDO 1 , EISHI MIYAZAKI 2 , AKIHIRO GOTO 1 , TAIKI MASUDA 1 , MARI YAMASUE 1 , TAKEHIRO HASHIMOTO 1 , KOHSUKE JO 1 , YUTAKA MUKAI 1 , HIROKI YOSHIKAWA 1 , TOSHIHIRO ISHIII 1,2 , RYU-ICHI TAKENAKA 1 , SATOSHI TOBA 1 , KAZUHIKO HASHINAGA 1 , HISAKO KUSHIMA 1 , KENJI UMEKI 1 , SHIN-ICHI NUREKI 1 , ISSEI TOKIMATSU 1 , KAZUFUMI HIRAMATSU 1 , JUN-ICHI KADOTA 1 1 Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Oita, Japan, 2 Center for Community Medicine, Oita University Faculty of Medicine, Oita, Japan Background We hypothesized that increased pulmonary vascular permeability may play a role in the pathogenesis of acute exacerbation of idiopathic interstitial pneumonia (AE-IIP). Angiopoietin-2 (Ang-2) promotes endothelial activation, destabilization, and inflammation. We examined whether Ang-2 expression would be associated with the pathogenesis of AE-IIP. Methods Twenty-three patients with AE-IIP, 18 patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS), 37 patients with idiopathic pulmonary fibrosis (IPF), and 33 healthy volunteers (HV) were enrolled. Serum levels of Ang-2 were measured by an enzyme-linked immunosolbent assay. Results Serum levels of Ang-2 in patients with AE-IIP and ALI/ARDS were higher than those in IPF and HV, and BALF Ang-2 levels were also higher than those in IPF. There was a positive correlation between serum Ang-2 levels and CRP in patients with AE-IIP, whereas a significant positive correlation was found serum Ang-2 levels and CRP or SOFA score in the patients with ALI/ARDS. Although the baseline Ang-2 levels did not relate to survival, Ang-2 levels significantly declined during treatment in survivor, but not in non-survivor. Conclusions Increased pulmonary vascular permeability and inflammation due to Ang-2 may play a role in the pathogenesis of AE-IIP. Background and Aim of Study Clinical course of interstitial pneumonia is often progressive with a poor prognosis. However, some groups of patients have relatively a stable clinical course. Clinical characteristics in patients with interstitial pneumonia whose respiratory functions had been monitored for more than ten years were retrospectively examined. Methods Nineteen patients admitted in our hospitals were enrolled in this study. Clinical background such as age, sex, underlying diseases and prognosis were examined. Respiratory function parameters at the first visit and annual changes were also examined. Results Patients consisted of 7 males and 12 female with 51.0 ± 2.2 years old, and follow-up periods were 15.11 ± 0.98 years. Eleven patients had collagen vascular disease, among which 6 patients had RA, and idiopathic nonspecific interstitial pneumonia was found in 6 patients. There were no patients with idiopathic pulmonary fibrosis (IPF), but one patient with idiopathic pulmonary upper lobe fibrosis and one with combined pulmonary fibrosis and emphysema (CPFE) were included in the study group. Annual decline of FVC in entire follow-up periods in all patients was 20.36 ± 8.66 mL, that was not significantly different from that of normal population. Conclusion Patients with interstitial pneumonia who survived more than 10 years had a stable ventilatory function. There were no patients with IPF who survived more than 10 years with the exception of a patient with CPFE. Background Alveolar epithelial cell apoptosis is involved in the pathogenesis of lung injury and pulmonary fibrosis. On the other hand, 'Epithelial Mesenchymal Transition (EMT)' of alveolar epithelial cells, that is induced by TGF-beta has been reported to play promoting role in the development of lung fibrosis. Bax is a pro-apoptotic member of Bcl-2 family proteins, and plays central role in mitochondria-dependent apoptosis. It is reported that Bax expression is increased in pulmonary alveolar epithelial cells of the patients of Idiopathic pulmonary fibrosis (IPF). However, the relation between Bax and EMT still remains unknown. Aim The purpose of this study is to investigate whether the control of Bax activity reduces apoptosis and EMT of alveolar epithelial cells in vitro. Method Murine pulmonary alveolar epithelial cells (LA-4 cells) and human pulmonary alveolar epithelial cells (A549 cells) were stimulated with bleomycin (BLM) for induction of apoptosis and EMT. The cells were pretreated with Bax inhibiting peptide V5 (BIPV5) before adding BLM. BIPV5 is designed to prevent the translocation of Bax into mitochondria by binding the N-terminal of the Bax in cytosol. Apoptosis was assayed with Flow cytometry. EMT was analyzed with Western blotting and Immunostaining. Results LA-4 cells and A549 cells underwent apoptotic change at 24 hours after stimulation of BLM. BIPV5 pretreatment decreased those apoptotic changes significantly. LA-4 cells and A549 cells underwent EMT change at 48∼72 hours after stimulation with BLM. BIPV5 pretreatment decreased those EMT changes significantly. Conclusion Control of Bax activation has an anti-apoptotic effect and an anti-EMT effect on lung epithelial cells.

E3: COPD 4 2-A2: OTHERS 2 at home for acute exacerbations of chronic obstructive pulmonary disease

Intermediate care-Hospital-at-Home in chronic obstructive pulmonary disease: British Thoracic Society guideline. BTS Guideline Development Group

Care delivery pathways for Chronic Obstructive Pulmonary Disease in England and the Netherlands: a comparative study

RESPIRATORY NEUROBIOLOGY AND SLEEP 1 PS395 PS408 PS420

Hospital re-admissions were needed for only 9 episodes (4.5%). However, 55 (21%) were associated with adverse events (clinical deterioration, hospital attendance or death: 9 patients chose to die at home). The range of HaH services rendered included patient education, care giver training, drug adjustments, oxygen therapy(19), non-invasive ventilation(4), financial advice, palliative care(21), treatment of co-morbities(16), social and emotional support. Conclusions A HaH service is effective in avoiding hospitalizations in the majority of cases. To optimize HaH outcomes, a wide repertoire of clinical skills and support services are required. The patients have advanced COPD and thus, HaH need capacity to cope effectively with adverse events.

We indicated clinical features of Pneumocystis Pneumonia (PCP) that developed during the treatment for Rheumatoid Arthritis (RA) in our hospital.

We reviewed retrospectively the patients who were admitted to our hospital, from 2002 to 2013 due to PCP. We confirmed the diagnosis of PCP by detection of Pneumocystis jirovecii by Grocott stain in respiratory specimens, detection of Pneumocystis jirovecii by PCR in respiratory specimens and pneumonia caused by other pathogens was excluded. Results Atotal of 10 cases were admitted to our hospital with laboratory-confirmed PCP during the treatment for RA. Our patients consisted of 4 males and 6 females with a median age of 74.1 years (range; 61 to 81 years). All patients were receiving corticosteroid therapy or immunosuppressant therapy. There were no patients receiving Trimethoprim-Sulfamethoxazole (TMP-SMX) for PCP prophylaxis. Nine patients was elevated plasma β-D glucan level on admission, but one patient was normal range. Three patients died with respiratory failure. There were no significant differences between survivors and non-survivors at the time of admission to our hospitals. Non-survivors showed rapid progression, and their periods from the admission to the death were in the range of 6 to 15 days. Conclusions RA patients treated with corticosteroid or immunosuppressant should receive TMP-SMX for PCP prophylaxis. We should always keep in mind the development of PCP during the treatment for Rheumatoid Arthritis in our hospitals. Background We reported allergic granulomatous vasculitis with eosinophil infiltration in an asthma model of C57BL/6 sensitized with ovalbumin <OVA>. TGF-β is thought to play an important role in fibroblasts proliferation and is critical to vascular remodeling in vasculitis. Rapamycin inhibits vascular endothelial cells proliferation and canalization. Objectives To elucidate the role of in vascular remodeling of allergic granulomatous vasculitis, we examined the effects of Rapamycin on the vasculitis of the murine model. Methods C57BL/6 mice <6-8 weeks> were sensitized with ovalbumin OVA and alum. The positive controls <n = 5> were exposed to aerosolized OVAdaily for 7 days. The other group of mice <Rapamycin treated mice <n = 5>> were administered with Rapamycin <0.5 mg/kg intraperitoneal administration> in parallel with daily exposure to aerosolized OVA for 7 days. On 7th day, bronchoalveolar lavage <BAL> was performed and the lungs were excised for pathological analysis. Cytokines in BALF were measured. Results While there was no significant difference of total cell number in BAL fluids between the control and the Rapamycin treated group, the ratio of eosinophils reduced significantly in the Rapamycin treated group. <mean: control group 83.2% vs Rapamycin group 70.3%> The concentrations of TGF-β in BAL fluids reduced significantly in the Rapamycin treated group. The pathological scores reduced significantly in the Rapamycin treated group compared to the control group. Intra luminal infiltration and proliferation of MIB1 positive myofibroblasts and α-SMA positive cells in pulmonary arteries were reduced dramatically in the Rapamycin treated group compared to the control group. Conclusion Rapamycin suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.

TAKESHI SARAYA 1 , KOH NAKATA 2 , KAZUHIDE NAKAGAKI 3 , DAISUKE KURAI 1 , HAJIME TAKIZAWA 1 , HAJIME GOTO 1 1 Department of Respiratory Medicine, Kyorin University School of Medicine, 2 Bioscience Medical Research Center, Niigata Univ. Medical and Dental Hospital, 3 

Background Human Mycoplasma pneumoniae (MP) pneumonia is characterized by alveolar infiltration withneutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area(PBVA). No mouse model has been able to mimic the pathological features seen in humanMP pneumonia, such as plasma cell-rich lymphocytic infiltration in PBVA.

To figure out the mechanism for inflammation by MP infection using a novel mouse model that mimics human MP pneumonia, mice were pre-immunized intraperitoneally with Th2 stimulating adjuvant, alum, alone or MP extracts withan alum, followed by intratracheal challenge with MP extracts. Results The toll-like receptor-2, which is the major receptor for mycoplasma cell wall lipoproteins, was strongly up-regulated in alveolar macrophages in a latter group after the pre-immunization but prior to the intratracheal challenge. Conclusion Acceleration of innate immunity by antecedent antigenic stimulation can bean important positive-feedback mechanism via alveolar macrophages in lung inflammation during MP pneumonia. Background and Aim of Study Bronchodilators such as beta2-agonists and anticholinergics are central to symptom management in COPD. Indacaterol is a novel, once-daily, inhaled long-acting beta2-agonist currently in development for the treatment of COPD. The improvement in forced expiratory volume in 1 second was seen as early as 5 min after inhalation of indacaterol. But the immediate effet of indacaterol on bronchodilation of patients with COPD is not fully understood. The forced oscillation technique (FOT) can determine respiratory system impedance, which consists of respiratory resistance (Rrs) and reactance (Xrs), and is measured over a wide range of frequencies during tidal breathing. We examined the immediate effect of indacaterol on COPD patients using FOT. Methods Mild to severe untreated COPD patients (n = 16) were recruited at Yamagata university Hospital (Yamagata, Japan). Rrs and Xrs were determined at 5 min prior to inhalation of indacaterol and at 2, 5, 10, 20, 40 and 60 min after inhalation using Mostgraph-01 (Chest MI, Inc, Tokyo, Japan). Results The value of Xrs at 5 Hz (Xrs5) and the difference between the maximal and minimal values of Xrs5 significantly increased at 2, 5, 40 and 60 min after inhalation compared with those of pre inhalation. The values of resonance frequency and area low Xrs significantly decreased at 2, 5, 40 and 60 min after inhalation compared with those of pre inhalation. Conclusion The Inhalation of indacaterol improved Xrs for two phases (2-5 min and 40-60 min after inhalation) in untreated COPD patients. Exacerbations are a prominent feature of the natural history of Chronic obstructive pulmonary disease(COPD). Quality of life is known associated with exacerbation. Patients with severe respiroatory distress, mortality is poor. This data and statistical analysis is still unknown to us in Korea. There is the Namdong Industrial Complex in Incheon. In April, Asian dust comes from china and Mongolia. Incheon is located near by this area. So Patients in Incheon may affect this season. We studied characterictics about seasonal and regional distribution of COPD exacerbations. Patients who met the current consensus of COPD definition were enrolled from January 2001 to December 2011 in Gachon University Gil Medical Center in Inchon, Korea. Retrospectively, we analyzed the clinical characteristics, pulmonary function test, cause of exacerbation, regional and seanal distribution. COPD has been divided mild (12.5%), moderate (40%), severe (34.3%) and very severe (13.2%) by the Global Initiative for Chronic Obstructive Lung Disease(GOLD). Male were 82.9%. Mean age was 73.1 years. Cause of exacerbation is pneumonia (55%), upper airway infection (17%), pneumothorax (4%), heart failure (1.5%) and lung cancer(1.3%). There is no regional distribution of COPD exacerbation in Incheon. COPD exacerbation have two peak in April(10.3%) and December(10.8%). 2.7% patients of exacerbation have experienced two or more per year. In conclusion, COPD exacerbation have two peak in April and December. There is no regional distribution of COPD exacerbation in Incheon. Pneumonia is main cause of COPD exacerbation.

JEONG-WOONG PARK, JONG HO AHN, SUNG HWAN JEONG Department of Pulmonary and Critical Care Medicine, Gachon University, Gi lMedical Center, Incheon, Korea Background Exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with decline in health status. A study was performed to investigate the demographic and clinical characteristics of patients with COPD exacerbations in South Korea. Methods A South Korean multicenter, observational study was performed, with a retrospective and prospective phase for 1 year each, in patients with COPD diagnosed by 2010 global initiatives for chronic obstructive lung disease (GOLD) criteria. We investigated demographic characteristics, all COPD exacerbations defined as events that require treatments with systemic corticosteroid and/or antibiotics (moderate) or hospitalization (severe), lung function via spirometric values, comorbidities and COPD assessment test (CAT) score. Results Among the 790 patients who completed the study, there were 401 patients (51%) with exacerbations of COPD for two years. The mean age, smoking history, and phenotype distributions were similar between exacerbators and nonexacerbators. However, body mass index (BMI) (p = 0.0164) and post bronchodilator forced volume in one second (FEV1) (p < 0.0001) were lower in exacerbators than in non-exacerbators. The mean CAT score (p < 0.0001) was higher in exacerbators (18.2(±8.1)) than in non-exacerbators (14.4(±7.6)). Likewise, the number of comorbidities (p = 0.002) was higher in exacerbators (327 cases) than in nonexacerbators (281 cases). The history of COPD (p = 0.0061) of exacerbators was longer than non-exacerbators. Conclusions This study found that a higher number of comorbidities and a higher mean CAT score are significantly associated with a higher rate of COPD exacerbations in South Korean COPD patients. Interestingly, this study showed that the BMI of exacerbators was lower than that of non-exacerbators. Background and Aim of Study Chronic Obstructive Pulmonary Disease (COPD), a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. COPD patients generally suffer from chronic hypoxemia. The aim of our study is to analyze effects of chronic hypoxia on hearing threshold. Method Out-patient pulmonary medicine clinic records and pure tone audiogram records were analyzed and patients whose age over 50 were included in our study. Data was recorded in Microsoft Excel and analyzes were made in SPSS version 16. Hearing threshold of 30 dB. or more was defined as hearing loss. Independent Samples T test and Chi-Square tests were used for statistical analyses. Results 96 pure tone audiogram records were analyzed in 1 year period (2011). 54 (65.1 ± 10.2 years) of patients were males and 42 (63.7 ± 8.5 years) of patients were females (P > 0.05). 70 (72.9%) patient had hearing loss and 6 (8.6%) of these cases had COPD diagnosis. 26 (27.1%) patient had normal hearing levels and 1 (3.8%) of these cases had COPD diagnosis (P > 0.05). Discussion Our analyses showed that hearing loss was more frequent in COPD patients but differences between two groups were statistically insignificant. Low number of patients might be cause for these results. More future prospective controlled studies are needed. Background and Aim Although asthma and chronic obstructive pulmonary disease (COPD) have been accepted as different diseases, many elderly patients show clinical features of both asthma and COPD, so called 'overlap syndrome (OS)'. The aim of our study was to examine the prevalence and clinical characteristics of the OS. Methods We conducted a retrospective survey of patients above 40 years old who had visited our hospital from January 2005 to June 2009 because of obstructive lung diseases. Patients with structural lung diseases or short duration of follow-up period were excluded. Based on lung function profiles, we classified subjects into COPD or OS group, and analyzed their prevalence, demographics, and lung function profiles. Results 2,105 subjects were included. 240 (11.4 %) and 630 (29.9 %) were found to have OS and COPD, respectively. The mean age was similar in both group (66.4 years old vs. 67.7 years, p = 0.553) but age of symptom onset was earlier in OS group than COPD group (38.4 years old vs. 58.2 years old, p < 0.001). The OS group showed lower baseline post-bronchodilator forced expiratory volume at 1 second (FEV1) than the COPD group (50.9 % vs. 57.7 %, p < 0.05). After additional treatment with tiotropium, the OS and COPD groups showed significant improvement of post-bronchodilator FEV1 (5.5 %, p < 0.05; 7.7 %, p < 0.001). Conclusion Certain proportion of elderly patients has the OS. Although their symptoms develop earlier and baseline lung function is worse, intensive treatment can improve lung function. Key Words asthma; chronic obstructive pulmonary disease; overlap syndrome; prevalence; clinical characteristics.

Objective and Methods To compare An' ningpai and eucalyptol on airway inflammation and mucous hypersecretion in cigarette smoked-exposed rats and to explore its mechanism, the indicators were compared between groups on rats airway inflammation, including bronchoalveolar lavage fluid (BALF) cell count, the expression levels of TNF-alpha, and IL-6, and detection of p38MAPK and p-p38MAPK protein levels. And combining with the MUC5AC expression level, the correlation between indicators were evaluated. To explore whether the effect of An' ningpai and eucalyptol on inflammatory mediators were related to p38MAPK phosphorylation. Results The anti-inflammatory effects was found in An' ningpai intervention group, and the inflammation index improved levels were significantly related with mucin improved levels. Compared with normal control group, increased BALF inflammatory cell count and expression of TNF-alpha, IL-6, were shown in smoke exposed group rats, accompaning by higher p38MAPK and p-p38MAPK protein levels. Compared with smoke exposed group, BALF inflammatory cell ratio and expression of TNF-alpha, IL-6, were obviously reduced by An' ningpai intervention, accompanied with higher p38MAPK and p-p38MAPK protein levels. And the p38MAPK and p-p38MAPK expression decreased, more obviously drop of p-p38MAPK suggested that An' ningpai had the effect of p38MAPK dephosphorylation. The anti-inflammatory effect of eucalyptol intervention group was similar to that of An' ningpai intervention group, no significant statistical difference showed. Glycerol as a drug control had no influence to the detection indexes. Conclusions During An' ningpai regulating airway mucociliary clearance function, the effects on inflammatory mediators were involved in at the same time. The induction dephosphorylated of p38MAPK may be the common mechanism of An' ningpai effect on regulation of mucin secretion and antiinflammation, in it, eucalyptol played a main role. Key Words An' ningpai; Eucalyptol; COPD; Rats exposed to cigarette smoke; MAPK. Rationale Patients with chronic obstructive pulmonary disease (COPD) often have some degree of hyperinflation of the lungs. Hyperinflated lungs can produce significant detrimental effects on breathing. Static lung hyperinflation has important clinical consequences in patients with COPD. The power of lung hyperinflation as measured by the inspiratory capacity-to-total lung capacity ratio (IC/TLC) was an independent risk factor for mortality in cohort study of patient with COPD. In this study, we prospectively look for the factors that affect hyperinflation of the lung. Methods Thirty eight COPD patients were grouped into two based on the ratio of IC/TLC. The IC/TLC value less than 25% was a predictor of higher mortality. The patients were analyzed for age, %FEV1 (FEV1/FEV1 predicted), duration of smoking, Body Mass Index (BMI) and frequency of exacerbation after six months using Student T test. Result Nine patients (23.7%) had ratio of IC/TLC ≤ 25% and 29 patients (76,3%) were more than 25%. Age, duration of smoking and frequency of exacerbations were not significantly related with lung hyperinflation. BMI and %FEV1 correlated significantly with lung hyperinflation. Conclusion Body Mass Index (BMI) and %FEV1 correlated significantly with lung hyperinflation. Keywords lung hyperinflation, IC/TLC. Background and Aim of Study This is a pilot study to measure DLCO-SB in COPD patients in Persahabatan Hospital. The aim of the study is to know the magnitude of disturbance in diffusing capacity of the lung in COPD patients. Methods This was an observational study in which COPD patients attending COPD-Asthma clinic in Persahabatan Hospital Jakarta were performed spirometry and DLCO SB consecutively from May 2013 to June 2013. Comorbid conditions were also identified. Results Spirometry and DLCO-SB measurement were conducted on 17 COPD subjects of which 14 subjects (82.4%) were COPD grade I-II and 3 subjects (17.6%) were COPD grade III-IV. The mean age was 67.65 (39-81); mean FEV1% was 58.12% (37.15-75.55), mean DLCO was 13.78 ml/min/ mmHg (6.82-31.37) and the mean DLCO% was 85.85% (43.41-140.48). The prevalence of decreasing in diffusing capacity of the lung in COPD patients was 23.5% (4 subjects), while 13 subjects were normal. Thirteen subjects (76.3%) had comorbid conditions. There were 2 subjects with mild decrease in DLCO and there was no significant correlation between comorbidities, grade of COPD, and obesity with the lung diffusing capacity abnormality. There was no significant correlation between age, FEV1% value, and Body Mass Index (BMI) with DLCO value. Conclusion The prevalence of decreasing in DLCO in COPD patients was 23.5%. There was no significant correlation between comorbidities, grade of COPD and obesity with lung diffusing capacity abnormality. There was no significant correlation between age, FEV1% value, and Body Mass Index (BMI) with DLCO value. Keywords COPD, spirometry, DLCO-SB, comorbidities, FEV1, BMI.

KOICHI TOMODA 1 , HIROMI KIMURA-SUDA 2 , KAORU KUBO 3 , MASANORI YOSHIKAWA 1 , HIROSHI KIMURA 1 1 Second Department of Internal Medicine, Nara Medical University, Nara, Japan, 2 Department of Bio-and Material Photonics, Chitose Institute of Science and Technology, Nara, Japan, 3 Laboratory Animal Research Center, Nara Medical University, Nara, Japan Introduction Osteoporosis is one of the comorbidities of chronic obstructive pulmonary disease (COPD). However the pathogenesis of the osteoporosis in COPD has not been fully elucidated yet. Bone strength reflects the integration of two main features: bone density and bone quality. We have investigated bone qualities in rats and mice with renal failure by Fourier transform infrared (FTIR) imaging and microscopic Raman spectroscopy. In this study we investigated bone quality in rats with emphysema by FTIR imaging and Raman spectroscopy. Methods Ten-week-old male SHR rats, fed with fiber free diet discontinuously were exposed to cigarette smoke twice a day for 8 weeks. After the last exposure, bone density in the femurs of the rats was measured by x-ray and DEXA, while bone quality was investigated by FTIR imaging and microscopic Raman spectroscopy (1064 nm). Results In the cigarette smoke exposed rats, emphysematous lesions with destruction and enlargement of alveolar walls were found. In these rats, bone mineral density measured by DEXA was significantly lower than those in control rats (non-smoked, continuously fed with control diet). In femur head X-ray image revealed bone density was lower than control rats. FTIR imaging showed decreased calcification in rats with emphysema. The decrease in calcification was more severe in trabecular than in cortical bone. Microscopic Raman spectroscopy showed the increase in carbonate-substituted hydroxyapatite, in spite of the reduction of the crystallinity in bone of rats with emphysema. Conclusion In rats with emphysema, bone quality as well as bone density was altered. The alteration in bone quality as well as the decrease in bone density may contribute to development of the osteoporosis in COPD.Rationale Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The receptor for advanced glycation end products (RAGE) is a multi-ligand cell surface receptor, reported to be involved in the process of acute alveolar epithelial cell injury. However, the role of RAGE in pulmonary emphysema is not well defined. We investigated the role of RAGE in the development of elastase-induced pulmonary emphysema. Methods RAGE sufficient (RAGE+/+) mice and RAGE deficient (RAGE-/-) mice were treated with intratracheal elastase on day 0. Airway inflammation, static compliance (Cst), lung histology and the levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid were determined on days 4 and 21.Results Neutrophilia in BAL fluid, seen in elastase-treated RAGE+/+ mice, was reduced in elastase-treated RAGE-/-mice on day 4, which was associated with decreased levels of KC, MIP-2 and IL-1beta. Cst values and emphysematous changes in the lung tissue were decreased in RAGE-/-mice compared to RAGE+/+ mice on day 21 after elastase treatment. Experiments using irradiated chimeric mice showed that the mice expressing RAGE on radioresistant structural cells but not hematopoietic cells developed elastaseinduced neutrophilia and emphysematous change in the lung. In contrast, the mice expressing RAGE on hematopoietic cells but not radioresistant structural cells showed reduced neutrophilia and emphysematous change in the lung. Conclusions These data identify the importance of RAGE expressed on lung structural cells in the development of elastase-induced pulmonary inflammation and emphysema. Thus, RAGE represents a novel therapeutic target for preventing pulmonary emphysema.

KARMEN KOKKINN 1 , DIEN DANG 1,2 1 The Royal Adelaide Hospital, Adelaide, South Australia, Australia, 2 Burnside War Memorial Hospital, Toorak Gardens, SA, Australia Introduction Dissociative Identity Disorder (DID), formerly known as Multiple Personality Disorder, is characterised by more than one personality state within an individual. Although the prototypical DID is distinguished by a dominant alternate identity(-ies) enforcing complete amnesia in the primary identity, there is a spectrum of amnestic qualities that are best described as 'overlapping identities'. The Polysomnographic (PSG) diagnosis of Idiopathic Hypersomnolence (IH) in an individual with DID has never been described. The symptomatic boundary state of DID has also never been described in sleep terms. Method We report a case of DID, and co-morbid IH. Patient A had a normal Epworth Sleepiness Scale (ESS) of 9/24 with phenomena more akin to Hypersomnolences of Central Origin. She described daytime 'identity overlapping' similar to her primary identity 'falling asleep', streams of consciousness interrupting her sleep entry and exit, frequent abnormal tactile and visual hallucinations suggestive of Hypnagogic Hallucinations, and recurrent symptomatic Sleep Paralysis. Her PSG and MSLT (off medications) was consistent with IH. Both her daytime and boundary symptoms improved with modafinil. Results The cardinal features of DID and Central Hypersomnolences may appear distinctly different, but some manifestations share common elements. Daytime sleepiness in DID may be misconstrued as the day-time shift in the dominant identity. Excessive Daytime Sleepiness and its psychiatric interpretations are amenable to modafinil. Discussion This is the first unique reported case of co-morbid IH in DID. These diagnoses may mutually co-exist. Alternatively they could be the same phenomenon at different ends of one spectrum: one occurring in isolation at the boundary of sleep, another occurring intermittently in both wake-and-sleep. Questions remain regarding where her alternate entities reside, and if Modafinil is in fact simply suppressing these. Background Obstructive sleep apnea (OSA) is a sleep disorder with repeated nocturnal desaturation and sleep fragmentation. It can lead to poor sleep quality, anxiety and depression. Our goal was to investigate short term (one month) and long term (six months) improvement of anxiety and depression in patients with different treatments of OSA. Methods This was a prospective, non-randomized and hospital-based study. There were 44 patients (Male/female: 38/6) suffering from OSA with definition of apnea/hypopnea index (AHI) >15/hr. The studied subjects were divided into three groups: surgery group(Uvulopalatopharyngoplasty, UPPP), CPAP group (continuous positive airway pressure) and no treatment group(even under doctor's encouragement). All subjects completed Beck Depression Inventory II(BDI-II), Beck Anxiety Inventory(BAI) and Pittsburgh Sleep Quality Index(PSQI) before treatment, 1 and 6 months after treatment. Result Compared to patients without treatment of OSA (no treatment group), surgery group and CPAP group had higher body mass index, scored higher inAHI and Epworth Sleepness Scale, whereas no difference in BAI, BDI and PSQI between group was registered. Only CPAP group had significant difference in BDI (p = 0.03) after one-month treatment. The surgery group and CPAP group had significant decrease in BDI (Surgery group: p = 0.025; CPAP group: p = 0.011) and PSQI (Surgery group: P = 0.027; CPAP group: P = 0.001) after six-month treatment. The CPAP group had significant difference in BAI (P = 0.043) after six-month treatment. However, no significant differences were present in BAI in surgery group after six-month treatment. No significant differences were either present in BDI, BAI and PSQI in no treatment group during 1 month or 6 months follow up. Conclusion CPAP can improve OSA patient's mood within one month treatment, as well as decrease anxiety, depression and improve sleep quality in six-month treatment. OSA patients have also significant improvement in measures of depression and sleep quality after surgical treatment in six months.

NORIKO KOYAMA 1 , MASANORI MATSUMOTO 2 , YUKIO FUJITA 1 , MOTOO YAMAUCHI 1 , KOICHI TOMODA 1 , MASANORI YOSHIKAWA 1 , YOSHIHIRO FUJIMURA 2 , HIROSHI KIMURA 1 1 Second Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan, 2 Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan Backgrand Patients with obstructive sleep apnea (OSA) have an increased risk of thrombotic cardiovascular events without CPAP therapy. We previously reported the loss of plasma high molecular weight-VWF multimers during sleep was related to the severity of OSA and low-level platelet consumption in patients with OSA (Koyama N et al, Eur Respir J, 2012). However, the relationships of intermittent hypoxia (IH) which characterize OSA and an increased risk of thrombosis have not been fully revealed. Aims To reveal the relationships of IH and VWF, we evaluated VWF releasing from human umbilical vein endothelial cells (HUVEC) under circumstance of intermittent hypoxia (IH) or normoxia. Methods HUVEC were exposed to 16 cycles/6 h, 32 cycles/12 h and 64 cycles/24 h of IH (5 min 1%O2/10 min 21%O2) or normoxia with cell culture system controlled by change of gases. After the exposure, the cell culture supernatants were collected. VWF antigens were measured with ELISA. Results The increased ratio of VWF in IH was 2.11 ± 0.04 and in normoxia was 1.82 ± 0.14 after 6 hours exposure. The increased ratio of VWF in IH was 2.72 ± 0.16 and in normoxia was 2.19 ± 0.12 after 12 hours exposure. The increased ratio of VWF in IH was 2.98 ± 0.33 and in normoxia was 2.29 ± 0.21 after 24 hours exposure. The increased ratio of VWF showed significantly higher in IH than normoxia in all exposure periods. Conclusion Intermittent hypoxic exposure enhances the release of von Willebrand factor from human umbilical vein endothelial cells. Objective to explore whether estrogen/Trx-1/Txnip-1 participates in protecting cells from injury under the condition of intermittent hypoxia. Methods ECV304 human umbilical vein endothelial cells (HUVECs) was used in this experiment. After 16 h intermittent hypoxia, Endothelial impairment was assessed through detecting proliferation and apoptosis by WST-1 methods and flow cytometry respectively. MDA and GSH content were measured by TBA and DTNB method respectively. ELISA method is used for measuring IL-6 and IL-8. Trx and Txnip mRNA levels were measured by real time-PCR. Results Compare with intermittent air(IA) group, apoptosis rate of HUVECs in intermittent hypoxia (IH), IH and estrogen administration (IHE2)group decreased (P = 0.0363), while the proliferation rate increased (P = 0.00358). The MDA levels in IH group were significantly increased and GSH decreased(P = 0.0038, P = 0.0006 respectively); MDA levels in IHE2 group was significantly lower than IH group, while GSH levels were higher (P = 0.0263, P = 0.0101 respectively). Compare with IA group, IL-6 and IL-8 levels in IH group were significantly increased (P = 0.0018, P = 0.0033 respectively); while the IHE2 group was significantly decreased (P = 0.0025, P = 0.0472 respectively). Except for the IAE2 group (1.92 ± 0.72), Trx-1 mRNAexpression of cells in IH group (2.47 ± 0.41) and IHE2 group (3.28 ± 0.45) was higher than IA group (1.72 ± 0.14) (p < 0.05) and Txnip-1 mRNA expression levels in IHE2 group (2.36 ± 0.55) was significantly lower than IA group (6.82 ± 0.66), IAE2 group (5.83 ± 0.26) and IH group (4.71 ± 0.59) (p < 0.05). Conclusions Estrogen/Trx-1/Txnip-1 pathway may participate in reducing oxidative stress and inflammatory response to protect cells from IH-induced injury. Background Poisonous snake bites are a common, fatal emergency in India. The aim was to treat patients with neuroparalytic snake bite using polyvalent Anti snake venom(ASV) along with ventilatory support and to assess outcome with respect to hospital survival, duration of mechanical ventilation, amount of ASV given and complications associated with mechanical ventilation or ASV. Methods The study included 58 patients with neurotoxic evenomation requiring mechanical ventilation for respiratory failure. They were administered 200 ml of polyvalent ASV. Outcome measures studied included hospital survival, duration of mechanical ventilation, amount of ASV given and complications associated with mechanical ventilation or ASV ventilation. Result All patients were administered an initial bolus dose of 200 ml ASV, followed by repeated doses of 100 ml ASV every six hours until signs of neurological recovery. Mean total dose of ASV administered was 412 ml. All patients were initially ventilated using Assist control(A/C) mode of ventilation. Mean duration of ventilation on A/C mode was 30.89 hours. 56 patients were weaned off successfully using pressure support ventilation. Mean duration of weaning was 7 hours. 4 patients developed Ventilator associated pneumonia 2 patients expired, one due to ventilator associated pneumonia and the other due to septicaemia. Conclusion We conclude that in the management, administration of a high initial bolus dose of 200 ml ASV and repeated doses of 100 ml ASV every six hours until signs of neurological recovery, supported by Assist control mode of ventilation resulted in an early recovery, a reduced total dose of ASV consumed, reduced the duration of mechanical ventilation, reduced the incidence of complications and was more cost effective.

HAZEL S. DELFIN, ALBERT P. ALBAY JR.

Critical illness polyneuromyopathy is a clinical disorder which is a significant source of ICU-related morbidity. It usually affects the lower limbs and leads to skeletal muscle weakness, leading to neuromuscular impairment, difficulty weaning from the mechanical ventilator and prolonged rehabilitation. We present a case of a 58 year old female admitted due to dysphagia with recent history of acute myocardial infarction, on statin and steroids for joint inflammation. Upon admission, patient was stable complaining of dysphagia and cough with difficulty in expectoration. At the wards she had dyspnea and hypotension and was intubated. Videofluoroscopic studies showed motility dysfunction. Total creatine kinase and creatine kinase MM were elevated. Electromyography nerve conduction studies showed severe motor and sensory denervation of the limbs indicating axonal dysfunction compatible with critical illness polyneuropathy. Patient was treated for sepsis from pneumonia, had aggressive glycemic control, weaned from the ventilator, referred to rehabilitation and improved. She was discharged with improved muscle strength with resolution of dysphagia. This case is unusual since it presented initially with bulbar palsy rather than weakness of the lower extremities. Results A total of 104 pneumothorax patients were reviewed. Their mean age was 39.7 years (SD ± 16.2 years) with a male to female ratio of 3:1. Commonest symtoms of pneumothorax was shortness of breath 103(53.3%) and abnormalities on physical examination was hypersonor 101(57.3%). Plain chest X-ray of pneumothorax patients showed hyperlucent avascular only 95(91.4%) and hyperlucent avascular with infiltrates 79(88.7%). Risk factors for the incidence of secondary pneumothorax obtained in this study were smoking 43(27.2%), pneumonia 42(26.6%), tuberculosis 37(23.4%), chest trauma 13(8.3%), iatrogenic 6(3.8%), lung malignancy 6(3.8%), COPD 5(3.16%), asthma 5(3.16%) and rheumatoid arthritis 1(0.6%). Commonest type of pneumothorax was secondary spontaneous pneumothorax 49(47.1%). Most of pneumothorax patients were successfully managed by chest thoracoscopy 98(82.3%). Outcome of pneumothorax patients were live 69(66.3%), died 35(33.7%). Causes of death in pneumothorax patients was respiratory failure 16(45.8%). Factors that worsen the survival rate of pneumothorax patients were chest trauma (HR = 3.49 (95% CI 1.52 to 8.04)) and pulmonary tuberculosis (HR = 3.33 (95% CI 1.39 to 7.99)). Conclusions Etiology of pneumothorax during hospitalization were smoking, iatrogenic, chest trauma, pneumonia, COPD, bronchial asthma, tuberculosis, rheumatoid arthritis, lung malignancy. Most types of pneumothorax was secondary spontaneous pneumothorax and pneumothorax patient's management was tube thoracostomy. Outcome of pneumothorax patients were live. Cause of death in pneumothorax patients was respiratory failure.

Factors cause pneumothorax is very important. Implementation of proper guidelines in cooperation of an interdisciplinary medical science and overall management of pneumothorax is necessary. aim of the study was to determine the characteristics of pneumothorax patients and factors affecting survival in Cipto Mangunkusumo National Center General Hospital. Methods Retrospective cohort study design was conducted on pneumothorax patients admitted in January 2000 to December 2011. Patients observed for 7 days regarding survival and factors influenced. Cumulative survival rate for 7 days was analyzed by Kaplan Meier and log-rank test. Cox proportional hazard regression was assign to calculate hazard ratio (HR). Results A total of 104 pneumothorax patients were reviewed. Their mean age was 39.7 years (SD ± 16.2 years) with a male to female ratio of 3:1. Commonest symtoms of pneumothorax was shortness of breath 103(53.3%) and abnormalities on physical examination was hypersonor 101(57.3%). Plain chest X-ray of pneumothorax patients showed hyperlucent avascular only 95(91.4%) and hyperlucent avascular with infiltrates 79(88.7%). Risk factors for the incidence of secondary pneumothorax obtained in this study were smoking 43(27.2%), pneumonia 42(26.6%), tuberculosis 37(23.4%), chest trauma 13(8.3%), iatrogenic 6(3.8%), lung malignancy 6(3.8%), COPD 5(3.16%), asthma 5(3.16%) and rheumatoid arthritis 1(0.6%). Commonest type of pneumothorax was secondary spontaneous pneumothorax 49(47.1%). Most of pneumothorax patients were successfully managed by chest thoracoscopy 98(82.3%). Outcome of pneumothorax patients were live 69(66.3%), died 35(33.7%). Causes of death was respiratory failure 16(45.8%) and factors that worsen the survival rate were chest trauma (HR = 3.49 (95% CI 1.52 to 8.04)) and pulmonary tuberculosis (HR = 3.33 (95% CI 1.39 to 7.99)). Conclusions Factors that worsen the survival rate of pneumothorax patients were chest trauma (HR = 3.49 (95% CI 1.52 to 8.04)) and pulmonary tuberculosis (HR = 3.33 (95% CI 1.39 to 7.99)).

Background and Aim of the Study Oxygen supply impairment due to acute physiological deterioration may increase the risk of poor prognosis, particularly in critically ill patients with inadequacy to compensate such changes. Pulse oxymeter is a rapid, simple and inexpensive tool that can be used to measure patient's initial oxygen saturation. The aim of the study was to evaluate peripheral oxygen saturation (SpO2) at admission in predicting the mortality of critically ill medical emergency patients in Cipto Mangunkusumo Hospital (CMH), a tertiary hospital referral center in Indonesia. Methods We performed a prospective cohort study of critically ill medical patients in resuscitation room, Emergency Department (ED) of CMH from October to November 2012. Subjects were divided into 2 groups according to their SpO2 which meassured at admission: group with admision SpO2 95% or above (1) and SpO2 less than 95% (2). The outcome was 30-day mortality. Log-rank test was used to analyze survival between groups. The risk of 30-day mortality was analyzed with Cox proportional hazard model. Results A total of 172 patients were included during the study. 30-day mortality was observed in 68 patients (39.5%). Patients with SpO2 less than 95% had a significantly lower survival rate [mean survival 22.8 (SE 3.77) days] compared to patients with SpO2 95% or above [mean survival 28.6 (SE 2.96) days], log-rank test p = 0.011. The hazard ratio of 30-day mortality was 1.8 (95% CI 1.10 to 2.87) in patients whose SpO2 fell below 95%. Conclusions Peripheral oxygen saturation below 95% at admission was significantly associated with increased risk of 30-day mortality. Given the ease of its measurement, SpO2 can be considered as a predictor of mortality in critically ill medical emergency patients. Objectives We investigated the effect of a nationwide educational program following surviving sepsis campaign (SSC) guidelines. Physicians' clinical practice in sepsis care and patient mortality rate for severe sepsis were analyzed using a nationally representative cohort. Methods Hospitalizations for severe sepsis with organ failure from 1997 to 2008 were extracted from Taiwan's National Health Insurance Research Database (NHIRD), and trends in sepsis incidence and mortality rates were analyzed. A before-and-after study design was used to evaluate changes in the utilization rates of SSC items and changes in severe sepsis mortality rates occurred after a national education program conducted by the Joint Taiwan Results The incidence rate of severe sepsis increased from 1.88 per 1,000 individuals in 1997 to 5.07 per 1,000 individuals in 2008. The cumulative mortality rate decreased from 48.2% for the pre-intervention cohort to 45.9% for the post-intervention cohort. The utilization rates of almost all SSC items changed significantly between the pre-intervention and post-intervention cohorts. These changes of utilization rates were found to be significantly associated with the reduction in mortality rate. Conclusion The nationwide education program through a national professional society has a significant impact on physicians' clinical practice and resulted in a reduction of severe sepsis mortality rate.

CHING-YI LEE 1,2 , WEI-CHANG HUANG 1 , JENG-YUAN HSU 1 , CHIEH-LIANG WU 1,3 1 Taichung Veterans General Hospital, Taichung, Taiwan, 2 Cheng-Ching Hospital, Taichung, Taiwan, 3 Background Acute respiratory distress syndrome (ARDS) is a serious and unusual complication of scrub typhus. This study was conducted to evaluate the clinical characteristics of patients with ARDS associated with scrub typhus. Methods This study retrospectively reviewed the medical records of patients diagnosed with scrub typhus at Pusan National University Hospital in Korea from January 1995 to December 2010. Nine patients with ARDS who were admitted to an intensive care unit (ICU) were included. Results The mean age of patients was 73.2 ± 7.3 yr and 7 patients (77.8%) were male. Seven patients (77.8%) were hospitalized at November (autumn in Korea) and the most common symptom was dyspnea (55.5%). ARDS was diagnosed 1.7 ± 2.4 days after hospitalization. Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score of patients was 20.7 ± 4.6 and 8.8 ± 3.0, respectively. Shock was developed in 5 patients (55.5%). 7 patients (77.8%) started treatment with doxycycline at the day hospitalized. The ICU and hospital mortality was 33.3% and 33.3%, respectively. Conclusion ARDS associated with scrub typhus occurs mainly in old aged persons at autumn. Due to high mortality, careful assessment and active treatment is needed in these patients. ; p = 0.001) and heart failure (43.1% vs 6.4%; p < 0.001). In CT group, there were more patients of empyema (0.7% vs. 22.6%; p < 0.001) and hemothorax (2.7% Vs. 12.9%; p = 0.013). Mean duration of drainage was 8.1 ± 8.4 and 9.2 ± 6.7 days in SBC and CT group (p = 0.443). Mean hs-CRP and APACHE-II score were comparable in the two groups. Complication occurred in 13 (8.9%) and 4 patients (12.9%) in SBC and CT group (p = 0.505). Twelve were pneumothorax in SBC group. One was blockage and improved with urokinase. In CT group, 1 catheter infection, 2 subcutaneous emphysema and 1 malposition occurred. There was no procedure related mortality in both groups. Conclusions The use of an SBC was as efficacious as CT in draining PEs in ICU. It was well tolerated by patients and was associated with no significant complications. It may be helpful to avoid repeated thoracentesis or the use of CT to drain uncomplicated PEs in an ICU.

Backgroud Acid-base unbalance is most common problem in severe ill patient, especially in condition of abnormal renal function state. Especially, metabolic acidosis is the most important clinical situation in patients with chronic kidney disease (CKD). The objective of this study is assess if venous blood gas (VBG) results are numerically similar to arterial blood gas (ABG) in acutely metabolic acidosis with CKD. Methods We prospectively correlated paired ABG and VBG in these patients from March, 2011 to september, 2012. We hypothesized that ABG results could be predicted by VBG results using a regression equation. Results We analyzed 125 patients (Women53) and mean arterial minus venous difference for pH, pCO2, and bicarbonate was-0.0170, 2.6528, and 0.6124. Bland-Altmanplot was done for predicting agreement of two groups, and the scale was pH-2.95 to 4.17, pCO2-4.45 to 9.76, bicarbonate-2.95 to 4.16, in 95% relative. Correlations between ABG and VBG were strong, at p = 0.90 for pH, 0.9 for pCO2 and 0.94 for bicarbonate. Conclusion The peripheral blood gas pH, pCO2, bicarbonate level is almost same as arterial blood gas analysis results. Therefore, VBG samples could be obtained in metabolic acidosis with CKD patients instead of ABG. Background and Aim of Study Non-Invasive Ventilation (NIV) has been shown to be promising for selected patients with acute respiratory failure. By eliminating the need for endotracheal intubation, NIV avoids complications such as ventilator-associated pneumonia. This study is a retrospective review of the indications and immediate outcomes of patients treated according to the acute NIV protocol during its first year of implementation. The protocol was created by this institution according to the American Thoracic Society guidelines, to promote the appropriate management of patients on NIV. Methods The institutional review board waived consent and approved this study. 193 patients were initiated on NIV for acute respiratory failure. A respiratory physician had to review each patient for appropriateness before NIV was initiated. NIV settings were reviewed at timed intervals, guided by the work of breathing and arterial blood gas results. The patients continued to be reviewed until they were weaned off NIV, intubated or died. . 13(6.7%) had other indications. By indication, the average initial pH ranged from 7.26 (neuromuscular weakness) to 7.44 (immunocompromised patient). The initial PaO2/FiO2 ratio ranged from 98 (immunocompromised patient) to 316 (neuromuscular weakness). Overall, 163 patients (84.5%) were successfully weaned off NIV within a median of 1.6 days (0.6-19.8), 23 (15.5%) were intubated and 7 died. The majority of those intubated, 11 patients, were immunocompromised patients. Conclusion Although NIV benefits immunocompromised patients by avoiding the complications of endotracheal intubation, the high failure rate (50%) of NIV in this group suggests that stricter criteria should be used when deciding between NIV and endotracheal intubation for an immunocompromised patient in acute respiratory failure.

Background and Aim of Study Antibiotic-resistant nosocomial infections are increasing rapidly. Selection pressure caused by previous antibiotic exposure is the major cause of drug resistance. Most previous studies on the emergence of resistance have focused on class of antibiotics, rather than considering more complex patterns of use. This has led to a paucity of data on dose-cumulative effects of long-term antibiotic exposure on the emergence of subsequent resistant infections This study was aimed to test the hypothesis that the antibiotic used to treat the initial infection and the time between antibiotic exposure and the onset of subsequent infection would have a significant correlation with the emergence of nosocomial drug resistant infections. Methods We retrospectively analyzed 167 mechanically ventilated patients with nosocomial infections over a 3-year period in our chronic respiratory care units, with focus on infections in the bloodstream, urinary tract, lower respiratory tract, and surgical sites. Results Of 167 patients, 62% were confirmed as antibiotic resistant. The most common isolated pathogen was extended-spectrum β-lactamase Enterobacteriaceae (43.9%), followed by methicillin-resistant Staphylococcus aureus (22.8%), and carbapenem-resistant Acinetobacter baumannii (17.5%). Multivariate analysis revealed that the association between resistance and the time interval increased within 10 days (odds ratio [OR] 2.45; P = 0.133) and peaked at 11 to 20 days (OR 7.17; P = 0.012). The data were categorized into 2 groups: when the time interval since exposure was more than 20 days, there was a 23.9% reduction in resistance rate compared with when the time interval was 20 days or less (OR 0.36; P = 0.002). Conclusions Although antibiotic exposure increased resistance rate in nosocomial infections, this association decreased as time interval increased. We suggest that future research use the time interval since the last day of previous antibiotic exposure as an important reference while investigating the evolution of subsequent antibiotic-resistant infections.

A 89 y/o female patient suffered from progressive shortness of breath for one month due to acute renal failure. Respiratory failure was occurred after admission and non-invasive ventilator was placed. However she suffered recurrent episodes of rapid bradycardia on removal of the mask. We have reviewed the literature and offer a potential mechanism for this phenomenon.Background and Aim of Study Idiopathic nonspecific interstitial pneumonia (NSIP) most frequently develops in middle-age, showing a good long-term prognosis. NSIP was originally subcategorized into cellular NSIP (cNSIP) and fibrotic NSIP (fNSIP). cNSIP consists primarily of mild to moderate interstitial chronic inflammation, usually with lymphocytes and a few plasma cells. However, some cNSIP incorporates alveolar epithelial changes. Then we have recognized epithelial injury pattern as a histologic pattern, which does not meet the histologic criteria for acute lung injury pattern in DAD and OP. To investigate the clinical characteristics of the epitherial injury pattern, we performed this retrospective analysis. Methods We regarded a pathological findings in cNSIP as epithelial injury pattern if there are at least one parameter as noted below. 1) Alveolar epithelial shedding and regenerative hyperplastic epithelia. 2) Obscured border between alveolar walls and lumen. 3) Membranous organization of the alveolar ducts and/or alveolar sac. A review of medical records between 2000 and 2010 identified patients who met the histological criteria with surgical biopsy and clinical criteria for cNSIP. Patients were divided into two groups: cNSIP with pathological epithelial injury and without. Results Of the 28 patients with cellular NSIP included in the study, 14 were with pathological epithelial injury and 14 were without. Five-year survival rate was 100% in both two groups. There seemed to be lower %FVC, lower %FEV1, lower %DLCO and lower PaO2 in cNSIP patients with epithelial injury pattern at the initial visit. Neutrophil count in blood test (P = 0.037) and neutrophil count in BALF (P = 0.037) were significantly higher in those patients. Conclusion The pathological findings of epithelial injury in cNSIP differ from the classic patterns of epithelial injury on acute lung injury pattern (DAD and OP). cNSIP patients with epithelial injury pattern were found severe at diagnosis, but showed good prognosis.

IKKOH YASUDA 1 , YOSHIO TAGUCHI 1 , EISAKU TANAKA 1 , TAKASHI HAJIRO 1 , MOONHEE HWANG 1 , SEISHU HASHIMOTO 1 , TAKEHIRO YASUDA 1 , YUSUKE KAJI 1 , TAKAHIRO TSUJI 1 , CHIE MORIMOTO 1 , TAKASHI INAO 1 , YUTO YASUDA 1 , SATOSHI NOMA 2 , YOICHIRO KOBASHI 3 1 Department of Respiratory Medicine, Tenri Hospital, Nara, Japan, 2 Division of Diagnostic Radiology, Department of Radiology, Tenri Hospital, Nara, Japan, 3 Department of Pathology, Tenri Hospital, Nara, Japan Background and Aim of Study Idiopathic pulmonary upper lobe fibrosis (IPUF) is a unique condition first described by Amitani, et al. in 1992. IPUF presents idiopathic and progressive pulmonary fibrosis predominantly in the upper lobe and subpleural regions. This study was performed to examine clinical and pathological characteristics. Patients and Methods Clinical, radiological, functional and pathological characteristics of 10 patients (7 males and 3 females) with IPUF were evaluated, restrictively excluded infections like Mycobacteriumspp. Results Body weight loss, history of pneumothorax and restrictive impairment of pulmonary function test were observed in 8, 9 and 9 patients respectively. In all patients predominant upper lobe volume loss was observed. Pathological findings were obtained in 8 patients. The fundamental histological features in the upper lobe were pleural thickening, parenchymal fibroelastosis, and the abrupt border between the fibroelastosis and the underlying normal lung parenchyma. In 6 of the 10 patients, however, interstitial changes were observed not only in the upper lobes, but also in lower lobes. Conclusion IPUF is a new concept, and it may also include subtypes with and without interstitial change in lower lobes that result in pulmonary fibrosis predominantly in the upper lobe.Background Some patients with idiopathic pulmonary fibrosis (IPF) are classified in novel disease concept, combined pulmonary fibrosis and emphysema (CPFE). In spite of the disease progression, vital capacity (VC) trends to be preserved in patients with CPFE. VC therefore may be not important parameter for predicting prognosis of IPF showing characteristics of CPFE. We previously reported that high levels of serum surfactant protein (SP)-D predict poor prognosis in IPF. Aim of this study is to evaluate value of SP-D in this subset of IPF. Subjects and Methods Seventy-two patients (pts) diagnosed as IPF according to the ATS/ERS statement were enrolled from 107 pts with interstitial pneumonia who visited Sapporo Medical University Hospital and Teine Keijinkai Hospital from 2007 to 2012. We defined "CPFE"pts who showed >25% emphysema on HRCT scan. The IPF pts were divided within two subsets; 34 of "CPFE" and 38 of "non-CPFE". Their medical records including pulmonary function tests and serum markers including SP-D were reviewed. Results In "CPFE", VC was preserved but diffusing capacity was decreased stronger than compared to "non-CPFE". "CPFE" showed significantly worse survival than "non-CPFE". Particularly, "CPFE" with severe worsening in annual change of diffusing capacity showed poor prognosis. Moreover, in "CPFE", higher serum SP-D group (more than 150 ng/ml) showed significantly worse survival than another group (p = 0.0089). Conclusion In IPF, "CPFE" pts showed significantly worse survival than "non-CPFE", especially the patients with high serum SP-D showed poor prognosis. It is suggested IPF patients with emphysema on HRCT and high SP-D level in sera should be needed careful observation. Background and Aim Interstitial lung disease in connective tissue diseases (CTD-ILD) is a leading cause of death in these patients. Herpesviruses infection has been associated with autoimmune diseases. However, it is still unknown whether infection with some of the viruses could initiate ILD in patients with CTDs. The aim is to determine the role of herpesviruses infection in initiation of ILD in connective tissue disorders. Methods Herpesviruses(HCMV,EBV,and HSV) infection was tested in the peripheral blood mononuclear cells (PBMCs), plasma and lung tissues of 62 patients with CTD-ILD, 19 patients with CTD(RA) and 33 healthy controls using quantitative PCR. T lymphecytes subsets and cytokines profile were analyzed by flow cytometry and liquid Chip. Results In patients with CTD-ILD, the detection rate of HCMV was significantly higher than that in healthy controls (41.94% vs. 6.06%, p = 0.000). The increased HCMV infection was not associated with administration of immunosuppressors and with different types of CTD-ILD. The patients with RA-ILD appeared to have a remarkable augment of HCMV infection compared with those with RA alone(50.00% vs. 10.53%, P = 0.022). The High frequencies of cytotoxic T cells accompanied with a reduced regulatory T cells (Tregs) were observed in the peripheral blood of CTD-ILD patients with HCMV infection, concomitant with markedly increased IL-6 and IL-10 levels and with a decreased ratio of TGFbeta to IL-6 level compared with those in the patients without HCMV(P = 0.003,p = 0.008,p = 0.017,respectively). The association of HCMV infection with the preceding indices to substantiate a pathogenic role for pulmonary function was assessed in the enrolled patients, showing lower percentages of FVC and DLCO observed in HCMV positive patients than in HCMV negative ones. High frequencies of cytotoxic T cells and reduced Tregs level combined with an increased IL-6 correlated highly with impaired lung function parameters. Conclusions HCMV may initiate ILD in situation of autoimmune disorders.

Background and Aim of Study Heme oxygenase-1 (HO-1) is a 32-kDa heat shock protein known as the heme-splitting enzyme with pulmonary cellular protection against oxidative stress and inflammation. It has been reported that HO-1 is upregulated in the lung of diffuse alveolar damage patients. Therefore, we examined whether serum HO-1 could be the biomarker for acute exacerbation of interstitial pneumonia (AE-IP) patients. Methods We measured serum HO-1 levels using sandwich ELISA method. First, we compared serum HO-1 levels of AE-IP patients with those of control subjects. Second, we evaluated the correlations between serum HO-1 and other biomarkers including serum LDH, WBC, CRP, SP-A, SP-D, KL-6 and PaO2/FiO2 ratio. Third, we evaluated the variations of serum HO-1 levels of AE-IP patients by treatments and compared serum HO-1 levels ofAE-IP patients who needed the steroid pulse therapy with those of who did not needed. Results 10 IP-AE patients were enrolled (M: F = 9:1). The mean age was 69.7 ± 10.3 yrs. 7 patients of AE of idiopathic pulmonary fibrosis and 3 patients of AE of collagen vascular disease were included. Serum HO-1 levels of AE-IP patients were higher than those of control subjects (61.7 ± 31.3 ng/mL, 33.2 ± 13.2 ng/mL (p = 0.0004)). Serum HO-1 levels of AE-IP patients before the treatment closely correlated with serum SP-A and LDH levels (R = 0.95, R = 0.84). Serum HO-1 levels of AE-IP patients significantly decreased in 7 days and 14 days after the treatment (both was p < 0.05). The mean serum HO-1 level of AE-IP patients who needed the steroid pulse therapy was 73.3 ± 11.9 ng/mL and that of those who did not needed was 44.3 ± 14.6 ng/mL. Conclusion Serum HO-1 might be able to serve as one of the biomarkers for the disease activity of AE-IP patients. Rationale Idiopathic pulmonary fibrosis (IPF) has an unknown etiology and poor prognosis. Several large-scale epidemiological studies have been previously conducted in western countries predominantly. It is important to determine the current IPF status in the Japanese population and compare it to that of western countries in order to evaluate racial and regional differences. Objectives To provide the epidemiological status of IPF and identify prognostic factors and causes of death in Japanese IPF patients. Methods We selected the island of Hokkaido (population, 5.5 million) as the epidemiological cohort of IPF among Japanese. On the basis of the clinical records of 553 IPF patients who were accepted the application of the Certificate of Medical Benefit between 2003 and 2007, we performed a retrospective epidemiological and prognostic analysis.

The prevalence and incidence of IPF was 10.0 and 2.23 per 100,000 people, respectively, with 72.7% predominance of males and the frequency increases with age. The median survival time was 35 months, and the most common (40%) cause of death was acute exacerbation. The most important factor influencing IPF prognosis was the percent vital capacity. Conclusions The status of IPF in the Japanese population was clarified for the first time through our report. Our results showed a lower prevalence and incidence rate in Japan compared with western countries. In men, the incidence of death due to acute exacerbation was higher in Japan than in western studies. These results may suggest racial and regional differences in IPF cases. The role of bronchiolar epithelial cells in the pathogenesis of idiopathic pulmonary fibrosis has not been addressed, although bronchiolar epithelial cells are known to compensate for alveolar epithelial cell loss and express various cytokines. We previously demonstrated that DNA damage and apoptosis were found at early phase of the bleomycin-induced pulmonary fibrosis in mice in bronchiolar epithelial cells, whereas at later phase in alveolar epithelial cells. Clara cells, which are dominant epithelial cells in peripheral airways, play progenitor roles for bronchial epithelial cells, and also play protective roles by expressing Clara cell 10 kD protein (CC10) against lung injury. The aim of this study is to elucidate the role of Clara cells in the development of pulmonary fibrosis. C57BL/6J mice were given intraperitoneal injections of naphthalene on day 0 to deplete Clara cells, and were given intratracheal injections of bleomycin or vehicle on day 2. Bronchoalveolar lavage fluids and lung tissues were obtained on day 16. Surprisingly, naphthalene-induced Clara cell depletion protected mice from bleomycin-induced lung injury and fibrosis. It has been reported that bleomycin upregulates the expressions of transforming growth factor (TGF)-β1 and high mobility group box 1 (HMGB1) in bronchiolar epithelial cells. Interestingly, naphthalene pretreatment suppressed the expressions of these molecules. These results suggests that depletion of Clara cells by naphthalene pretreatment reduces the production of profibrotic mediators by regenerated bronchiolar epithelial cells in the development of bleomycininduced pulmonary fibrosis in mice. We conclude that Clara cells are likely to play a promoting role in the pathogenesis of lung injury and fibrosis. Background Gene-expression profile analyses of interstitial lung diseases (ILDs) revealed that ROS1 was transactivated in majority of ILDs. ROS1 is a receptor type tyrosine kinase which is known as a driver mutation of human lung cancer. However, the biological significance of ROS1 in ILDs and its clinical potential as a therapeutic target for ILDs were not yet been studied. Methods ROS1 immunoreactivities were quantitated 23 lung biopsy specimens obtained from patients with ILDs (7 idiopathic pulmonary fibrosis, 6 non-specific interstitial pneumonia and 10 chronic hypersensitivity pneumonitis). In addition, immunoreactivities of ROS1 in the lung specimens obtained from bleomycin-induced pulmonary fibrosis and control lung were also evaluated. Results In lung biopsy specimens obtained from patients with ILDs, ROS1 was detected mainly in the alveolar epithelium surrounding areas of fibrosis in ILDs. Immunohistochemical positivities of ROS1 were correlated to gene expression profiles of ROS1 in microarray. ROS1 was remarkably expressed in the lung specimens obtained from bleomycin-induced pulmonary fibrosis than those from control. Conclusion We conclude that ROS1 is up-regulated in the lung epithelium of ILDs. The results of this study support the potential of ROS1 to be a therapeutic target for ILDs. Background Interstitial lung disease (ILD) includes a large, heterogeneous group of mostly rare pulmonary conditions that cause derangements of the alveolar walls and loss of functional alveolar capillaries. Familial ILD is a rare type of hereditary disease. It becomes explicitly rare and multifaceted when the main cause is another familial type of disease, familial juvenile idiopathic arthritis. Several factors should be considered, since it is exceptionally atypical in nature and are rarely encountered in practice. Proper treatment should be given to decrease the mortality among children. Case This is a case of an 8 year old girl, presented with difficulty of breathing, with swelling of fingers, ankles and knees and had respiratory distress when she was 2 years old. Initially diagnosed as miliary tuberculosis however workups done such as Chest CT scan and open lung biopsy revealed ILD. RF factor was increased, and antidsDNA was equivocal. She had relatives who died with unknown cause, her eldest sister died of unknown diagnosis presented with respiratory distress when she was 1 year and 3 months old. Her 3rd sibling was diagnosed with SLE with overlapping JIA at 3 years old and was diagnosed with ILD. Presently maintained on steroids and sildenafil for the pulmonary hypertension. Conclusion The diagnosis of interstitial lung disease is challenging. In this report we describe a rare type of familial ILD in Filipino children. Searching for the known etiology of such disease requires a thorough history and a complete physical examination. Presently underreported and misdiagnosed cases are usually seen in our clinical settings, thus vigilant actions should be done in order to decrease morbidity and mortality among children. Background Alveolar epithelial cell damage and apoptosis has been reported to play important roles in the pathogenesis of acute lung injury (ALI) in various animal models and human cases of ALI. Amphiregulin (AR) is a member of the epidermal growth factor family that contributes to regulate cell proliferation. We previously reported that AR attenuates BLM-induced lung injury. And AR was found to be upregulated in lung epithelial cells in ventilatorassociated lung injury model. However, the role of amphiregulin in lung injury still remains elusive. Aim The aim of this study is to investigate into the effect of AR in murine model of lipopolysaccharide (LPS)-induced acute lung injury. We investigated the effect of AR in vitro using the murine lung alveolar type II epithelial cell line LA-4 as well.

Methods 7-wk-old female C57BL/6 mice were treated with intraperitoneal injection of human recombinant AR or phosphate buffered saline, three times before and after (−6h r, −0.5 hr, +3 hr) intranasal administration of LPS. Histological evaluation of the lung tissue and analysis of the bronchoalveolar lavage fluid (BALF) were performed at 6 and 24 hours after LPS injection. LA-4 cells were cultured in the presence of 0, 10 or 100 nM of AR. After 3 hours incubation, LA-4 cells were rinsed and 50 μg/ml of LPS was added. After 24 hours incubation, cells were harvested and used for apoptosis analysis on a flow cytometer and western blotting. Result Human recombinant AR significantly decreased TUNEL-positive cells in lung tissues. AR also decreased total cell counts, neutrophil counts and protein concentration in BALF from of LPS-injected mice. LPS induced apoptosis on LA-4 cells, and AR suppressed this apoptosis rate through inhibiting a caspase-8 activity. Conclusion AR is likely to have a protective effect on acute lung injury. AR treatment might be one of new therapeutic approaches for ALI.

Rheumatoid arthritis associated interstitial lung disease (RA-ILD) occurs 10% to 30% of patients with rheumatoid arthritis (RA) and is associated with increased mortality in up to 10% of patients with RA. However, little is known about the mechanisms of pathogenesis in RA-ILD. Gelsolin is one of actin binding proteins which regulate cell structure and metabolism. Recently, increased gelsolin expression is shown to have a role in pulmonary inflammation and fibrosis. The aim of this study is to investigate the proteins related to UIP pattern by comparing to OP pattern in RA-ILD using proteome analysis of bronchoalveolar lavage fluid (BALF). Methods BALF samples were obtained from 13 patients with RA-ILD in our hospital between 1999 and 2011. We divided them into two groups, namely UIP pattern and OP pattern by findings of high resolution computed tomography. Five patients with UIP pattern and 8 patients with OP pattern were examined. BALF samples were concentrated by acetone precipitation and separated by 2-dimensional electrophoresis. Gels were stained with SYPRO Ruby Protein Gel Stain and scanned with FluoroPhoreStar 3000. Proteins were identified by referring to the published BALF maps and/or by LC-MS/MS. Results In comparison of individual BALF samples, gelsolin and immunoglobulin kappa chain C were significantly higher in the patients with UIP pattern than OP pattern. In contrast, C-reactive protein, haptoglobin, surfactantassociated protein A, and alpha-1 antitrypsin were significantly higher in the patients with OP pattern than UIP pattern. Gelsolin, which was significantly higher in UIP pattern, was shown to be C-terminal half of gelsolin. Conclusion We identified several proteins that might have roles in the clinical differences between UIP and OP patterns of RA-ILD. C-terminal half of gelsolin might contribute to pulmonary fibrosis in RA-ILD. Rationale Circulating fibrocytes are thought to contribute the fibrogenesis in the lungs. However, the function of fibrocytes in pulmonary fibrosis remains unclear. Here we examined whether fibrocytes regulate the function of lung fibroblasts. In particular, we focused on production of growth factors from fibrocytes. Methods We used 3H-thymidine incorporation assay to examine the growth of fibroblasts co-cultured with fibrocytes. Western blotting was performed to evaluate the myofibroblast differentiation. The concentrations of growth factors in fibrocyte culture medium were measured by ELISA. The inhibitory responses by neutralizing antibodies for each growth factor were examined. Immunofluorescence staining was performed to detect fibrocytes and growth factors in fibrotic lung tissues of patients with idiopathic pulmonary fibrosis. Results Fibrocyte co-culture induced the growth and myofibroblast differentiation of human lung fibroblasts. Increased levels of growth factors were observed in fibrocyte culture medium. PDGF-BB and FGF-2 contribute to the growth-stimulating activity of fibrocytes, and TGF-beta and FGF-2 played roles in the stimulatory activity of fibrocytes in myofibroblast differentiation of fibroblasts. Background Pulmonary fibrosis is characterized by progressive worsening of pulmonary function leading to a high incidence of death. Currently, however, there has been little progress in the therapeutic strategies for pulmonary fibrosis. There have been several reports on cytokines being associated with lung fibrosis, including IL-6, TGF-β1. We recently reported two substances (ATRA and thalidomide) had preventive effects on pulmonary fibrosis by inhibiting IL-6-dependent proliferation and TGF-β1-dependent transdifferentiation of lung fibroblasts. Rheumatoid arthritis is a chronic autoimmune disorder, and its pathogenesis is also characterized by an association with several cytokines. It has been reported that Calpain, a calcium-dependent intracellular cysteine protease, plays an important role in the progression of Rheumatoid arthritis. In this study, we examined the preventive effect of Calpeptin, a calpain inhibitor, on bleomycin-induced pulmonary fibrosis. Methods We performed histological examinations and quantitative measurements of IL-6, TGF-β1, collagen type Iα1, and angiopoietin-1 in bleomycin treated-mouse lung tissues with or without the administration of Calpeptin. Results Calpeptin histologically ameliorated bleomycin-induced pulmonary fibrosis in mice. Calpeptin decreased the expression of IL-6, TGF-β1, angiopoietin-1, and collagen type Iα1 mRNA in mouse lung tissues. In vitro studies disclosed that Calpeptin reduced 1) production of IL-6, TGF-β1, angiopoietin-1 and collagen synthesis from lung fibroblasts, and 2) both IL-6dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis. Conclusions These data suggest the clinical use of Calpeptin for the prevention of pulmonary fibrosis.

HIROKUNI HIRATA 1 , MASAFUMI ARIMA 1,2 , TATSUYA YOKOYAMA 1 , TAKUYA KAKUTA 1 , MASAMITSU TATEWAKI 1 , FUMIYA FUKUSHIMA 1 , NARUO YOSHIDA 1 , YOSHIKI ISHII 1 1 Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University, 2 Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba, Japan Background and Objective Synthesis of cysteinyl leukotrienes (cys-LT) is thought to cause inflammatory disorders such as bronchial asthma and allergic rhinitis. Recent reports have suggested that leukotriene C4 (LTC4) is an important regulator of pulmonary fibrosis. This study examined the effect of LTC4 in LTC4 synthase-overexpressed transgenic mice with bleomycininduced pulmonary fibrosis. The function of lung-derived fibroblasts from transgenic mice was also investigated. Methods Bleomycin was administrated to transgenic mice and wild-type (WT) mice by intratracheal instillation. Concentrations of interleukin (IL)-4 and -13, interferon-gamma, and transforming growth factor (TGF)-beta1 in bronchoalveolar lavage fluid were measured 1, 3, 7 and 14 days after the administration of bleomycin. Lung tissue was examined histopathologically on day 14. In addition, lung-derived fibroblasts from transgenic and WT mice were cultured for 7 days. Expression of TGF-beta1 mRNA was measured by realtime polymerase chain reaction. Results Both the pathological scores for pulmonary fibrosis and the levels of IL-4, IL-13 and TGF-beta1 on day 14 were significantly greater in transgenic than in WT mice. Furthermore, the reduction of LTC4 by pranlukast hydrate, a cys-LT1 receptor antagonist, in fibroblasts from transgenic significantly decreased the expression of TGF-beta1 mRNA compared with those from WT mice. Conclusions Overexpression of LTC4, amplifies bleomycin-induced pulmonary fibrosis in mice. Our findings suggest a role for LTC4 in lung fibrosis.