key: cord-0042014-3gdfo6vd
authors: nan
title: TSANZ Oral Abstracts
date: 2010-03-01
journal: Respirology
DOI: 10.1111/j.1440-1843.2010.01735.x
sha: fca590c4745c3414566c98c8639b26a1c11bdfd6
doc_id: 42014
cord_uid: 3gdfo6vd

nan

Introduction Very little is known about adult health of survivors of extreme preterm birth. The aim of this study was to assess the burden of respiratory symptoms in a cohort of young adults born prematurely compared to sibling controls. Method One hundred and fifty six children born prematurely (26-33 weeks gestation) at the Mater Hospital Brisbane between [1989] [1990] were mailed questionnaires to assess their respiratory symptoms using a modified version of The European Community Health Survey. Term-born siblings were invited to act as controls.

Results Thirty six responses were received (23%). The studied cohort consisted of 36 cases (64% female) and 17 controls (59% female). The median age was 19 years (18 -21) in the cases and 18 years (16 -27) in the control group (p = ns). Shortness of breath (SOB) was reported in 25% of the preterm cases, but nil in the control group (p = 0.044). There was a higher incidence of day/night cough (50% vs. 13%, p = 0.0135) and morning cough (37% vs. 0%, p = 0.0045) in the preterm cases compared to controls. The preterm cases were also more likely to experience a chest infection before the age of five (38% vs. 13% of controls, p = 0.046). SOB was unrelated to a history of asthma, atopy, exposure to smoke or domestic animals as there was no difference between controls and cases. Conclusion A higher incidence of SOB was reported in young adults who were born prematurely compared to sibling matched controls, and this appears to be unrelated to asthma and atopy. Further subjects will be enrolled interstate to assess predictors of respiratory symptoms in early adulthood. Background Currently all protocols for checking patient readiness for oral intake post fibre optic bronchoscopy (FOB) are non-evidence based. There is a need to establish the shortest safe time to implement resumption of oral intake following administration of local anaesthesia for various reasons. We examined return times for the gag reflex and swallow response. Method A prospective study of 100 consecutive patients presenting for a FOB, age 18-86, were assessed for optimum time to check the gag and swallow reflex. The gag was checked pre and post FOB by the touch method (tickle back of throat), swallow was checked post FOB with a sip of water at various times. Results After 1 hour 67% and 90% of patients had a gag reflex (n = 82) and swallow response (n = 100) respectively. This increased to 88% and 96% at 1½ hours, 95% and 99% at 2 hours, 100% and 100% at 2½ hours. The amount of sedation or length of procedure did not correlate with the return of the gag reflex or swallow response. None of the patients who swallowed with the gag still absent coughed or aspirated. Eighteen patients did not have a gag reflex pre FOB. Conclusion The gag reflex and swallow response are separate. Data shows it is possible to swallow safely without a gag reflex. The time to safe swallow is much shorter than recommended in current protocols. However, we consider it safer to allow oral intake when both reflexes are present, if the gag is present pre FOB. Otherwise the patient should wait for 1½ hours post FOB as 88% have a returned gag reflex, if swallow response is also back. Nomination None.

Introduction Home monitoring in COPD may identify acute exacerbations earlier, enabling prompt treatment, thus improving morbidity and mortality. Reactance (X rs ), measured by forced oscillation technique has a potential role in home monitoring. The aim of this study was to determine within-and between-day repeatability of resistance (R rs ), X rs , and spirometry in stable COPD subjects. Methods Ten COPD subjects underwent seven consecutive home visits consisting of three measures of FOT (1 minute recording) and spirometry before and after 200 mcg ventolin via spacer. Results Subject characteristics Mean (SD) -Age 74.7 years (7.43), smoking history 48.6 pack years (17.3), post-BD (post-bronchodilator) FEV1 51.1% predicted (16.3), FEV1/FVC ratio 0.4 (0.11). Repeatability measures are reported as intra-class correlation coefficient (ICC) and SD of within subject variance (Sw). Introduction Chronic obstructive pulmonary disease (COPD) is the single most important risk factor for lung cancer (affecting 50-90% of those diagnosed). Considerable overlap exists between smokers who develop COPD and/or lung cancer, suggesting involvement of shared pathogenic pathways (inflammation, matrix remodeling and cell death). In a prospective study of high and low risk smokers we have combined SNPs from GWAS and candidate gene studies to develop a susceptibility score for lung cancer (LCSS).

Methods Seven hundred and twenty eight high risk individuals (chronic smokers, >40years old, >20 pack years, spirometric confirmed COPD), and 484 smokers without COPD were recruited and followed for a mean of 5 years. Cohorts were matched for smoking history, ethnicity, gender and age, thereby excluding confounding from these variables. All volunteers completed spirometry, modified ATS respiratory questionnaire and gave blood for DNA. iPLEX and Taqman systems were used to genotype the SNP panel. cases are in the high risk (COPD) cohort (6% over 5 years, mean score = 6.3) and 11 (21%) from the low risk cohort, normal lung function (2% over 5 years, mean score 3.4). The healthy unaffected smokers' mean score was 2.3. This prospective study confirms the risk status assigned by the LCSS with 41 (6%) vs. 11 (2%) lung cancers over the 5 year follow up (OR = 2.6 (%% CI 1.3-5.4, p = 0.005).The performance characteristics of the LCSS reported here, confirm its utility, in correctly identifying smokers at greatest lung cancer risk.

Conclusion In this prospective study, we show that the LCSS identifies those at greatest risk of lung cancer who might benefit from aggressive preventive strategies such as cessation and chemoprevention. The author is not aware of any conflict of interest. Malignant mesothelioma (MM) remains an incurable cancer and its global incidence is rising rapidly. Alternative therapeutic strategies are therefore required. Bacterial products have been trialled in an effort to enhance local immunity and have demonstrated tumouricidal activity. Staphylococcal enterotoxins (SE) are classic models of superantigens that have potent mitogenic activity on T cells and demonstrated anti-tumour effects in several cancer models. Intrapleural delivery of staphylococcal enterotoxin C (SEC) has been used in China for many years as a pleurodesing agent. However, it is unknown whether SEC actually kills cancer cells. In this study, we examined the efficacy of SEC in the treatment of MM. SEC was added at various concentrations (0-10 ng/ml) to several human and murine MM cell lines and a human benign mesothelial cell line in vitro. Dose dependant cytotoxicity was observed in all cell lines resulting in a significant reduction in viability at higher doses (10 ng/ml) when using trypan blue exclusion and WST-1 assays (0.001 < p < 0.05). In an effort to elucidate the mechanism of action of SEC, annexin V staining and flow cytometry were used to measure apoptosis. Results demonstrated a significant increase in apoptosis in MM cells when treated with SEC compared to untreated controls (0.001 < p < 0.05). On the contrary, benign mesothelial cells appeared to be resistant to the apoptotic effects of SEC at equivalent concentrations (p > 0.05). ELISA based assays were used to examine cytokine profiles in culture supernatants of SEC treated MM cells and benign mesothelial cells. Levels of the pro-inflammatory cytokine IL-8 decreased in SEC treated MM cells (0.001 < p < 0.01) compared to a significant increase in levels observed in benign mesothelial cells (0.01 < p < 0.05). These results suggest that SEC kills MM cells in vitro with some specificity and its activity against MM in vivo warrants investigation.

Conflict of Interest No.

Purpose We examined age trends in the distribution of stage at diagnosis in patients presenting with non-small cell lung cancer (NSCLC) at tertiary hospitals.

Methods We used the Queensland Integrated Lung Cancer Outcomes Project (QILCOP), a clinical registry which collects information on about 40% of all lung cancer patients in Queensland, to analyse the distribution of clinical (TNM) stage among 3,283 patients diagnosed with NSCLC between 2000 and 2005. Differences in stage distribution across age were analysed using tests of proportions and multivariable logistic regression with stage as the dependent variable and other demographic characteristics as covariates.

Results The median age at diagnosis of patients in the study was 68 years (range 26-95) and 68% were males. The overall proportions of stages I, II, III, and IV were, respectively, 30%, 9%, 29%, and 32%. The percentage of stage I disease increased with age (p < 0.001), from 19% in those younger than 55 years to 26%, 31%, and 37% in those aged 55-64, 65-75, and 75 years or older, respectively. Age differences in stage distribution remained significant in multivariable analysis controlling for gender, rural residence, and socioeconomic status. Among the other characteristics, only gender differences in stage was significant, with stage I cancer being more common in women compared to men (34% vs. 29%, p = 0.02). Australia has the world's highest incidence of mesothelioma, a disease which has no proven effective therapy. The median survival of less than 12 months and five year survival of 5% have not changed in two decades. Radical resection has a high attrition rate with most cases recurring locally, and few patients have durable responses to chemotherapy. Symptoms are related to local disease which compresses the lung and causes severe chest pain from enlarging tumour masses. Aim To improve local control of mesothelioma by high dose radiotherapy using advanced technologies that precisely define the active tumour and reduce toxicity to normal tissues. Methods All patients had 18 FDG PET scans co-registered with a simulation CT scan to define the target volume, and follow-up PET scans were analysed to assess the residual total glycolytic volumes (TGV) after radiotherapy. Acute and long term toxicities were assessed.

Results Between 2003 and 2009 thirty patients with incompletely resected pleural mesothelioma were treated with radiation doses of 30 to 60 Gy to part or all of one hemithorax. All patients who received chemotherapy had progressed prior to radiotherapy. In 2006 we introduced a program using a new technique called intensity-modulated radiotherapy (IMRT). TGVs reduced by 60% after radiotherapy, median survival was extended to 24 months and there were no major radiation toxicities, the most common being grade two pneumonitis. Relapses were frequent on extended follow-up, the majority in areas outside the radiotherapy field.

Conclusions IMRT is effective in maximising local control in mesothelioma patients who have had extrapleural pneumonectomies, and for selected patients with an intact lung. Toxicities are manageable and locoregional control is very good. High dose radiotherapy is recommended for most mesothelioma patients for long term palliation and control of locoregional progression.

Introduction Mortality benefits for LDCT screening are not yet known. The Queensland Lung Cancer Screening Study is screening up to 750 high risk volunteers based on the NLST/ACRIN protocol. Aims Observational cohort study to assess: disease detection rate; lung nodule work-up; cost; quality of life issues; smoking cessation; biomarker collection feasibility. Methods Recruitment via local advertisement and press release. Major inclusion criteria: age 60-74 years; smoking history ‡30 pack years; fit for surgery. Volunteers have one prevalence and two incidence scans and follow-up for three more years. LDCT parameters: Phillips Brilliance 64 slice multidetector scanner; low-dose protocol; 0.9mm slice width. Scan reporting: two radiologists independently; independent CAD reading (Phillips Brilliance software); final report is agreed by consensus.

Results See Table 1 -to be updated. Magnetic resonance imaging (MRI) is a useful modality for assessing chronic thromboembolic pulmonary hypertension (CTEPH) before pulmonary endarterectomy (PEA). Cardiac MRI provides more accurate right ventricular (RV) data than echocardiography. MR angiography demonstrates vascular changes reliably to a segmental level and MR perfusion shows disease distribution. Aim To examine the relationship between changes in MRI parameters with clinical and haemodynamic outcomes post-PEA. Methods RV end-diastolic volume (RVEDV), RV ejection fraction (RVEF), vessel abnormalities and lobar perfusion defects were determined with MRI before and after PEAs performed during [2004] [2005] [2006] [2007] . Changes in New York Heart Association (NYHA) functional class, six minute walk distance (6MWD), mean pulmonary artery pressure (mPAP) and cardiac output (CO) were collected retrospectively from patient charts. Results Nineteen patients assessed pre-PEA were of mean ± SD age 57 ± 12 years, NYHA class 2.8 ± 0.7, 6MWD 414 ± 103 metre and mPAP 42±10 mmHg. Immediately post-PEA, mPAP fell by 13 ± 7 mmHg which was related to changes in RVEDV of 26 ± 15% (r 2 = 0.38, p = 0.006). At 6-12 months post-PEA, 6MWD improvement (115 ± 99 metre) was related to changes in RVEF of 28±49% (r 2 = 0.40, p = 0.007) but angiographic changes had a weak relationship with NYHA class shift (r 2 = 0.22, p = 0.034). Perfusion generally improved after PEA relating weakly with RVEDV (r 2 = 0.3, p = 0.032) but not clinical outcomes. Conclusions This study shows that improvements in MRI parameters (RV data more than angiographic findings) after PEA correspond to clinical and haemodynamic outcomes. We have demonstrated a useful imaging test for monitoring patients post-PEA with no radiation exposure. Purpose Allergic reactions to antibiotics are very common in cystic fibrosis (CF) patients and can complicate treatment in patients with multi-or pan-resistant bacterial species. We hypothesised that post-transplant immunosuppression may reduce the requirement for desensitisation. Methods and Materials A retrospective review was performed in June 2009 to detect prescribing practices and any changes in allergy patterns before and following lung transplantation in CF. Since antibiotic desensitisation has not been used post-transplant at our institution, our aim was to review our experience with antibiotic rechallenge, without desensitisation, in the post-transplant setting. Results Fifty eight CF patients, 34 (58%) female, aged 34 years, range 15-50 years, 3 heart-lung, 3 heart-lung liver have undergone transplantation at our institution. 36 (62%) had a pre-transplant history of IgE (angioedema -8%) or non-IgE (e.g. rash, nausea, arthralgia or liver dysfunction -92%) mediated reactions to at least one antibiotic (29 % penicillin, 21 % cephalosporin, 13 % carbapenem, 9% aztreonam and 28% others). Desensitization to antibiotics with non IgE mediated reaction was attempted in 9 out of the 36 patients pre-transplant and successful on all occasions. In 27 other patients, alternative antibiotics were selected and desensitisation was not required. After transplantation, 18 (50%) patients with non IgE mediated reactions were rechallenged without desensitisation on 25 occasions. No life-threatening reactions were observed. Only two episodes required antibiotic cessation and both recovered without incident. New onset of adverse reaction to IV colistin and voriconazole occurred in two patients following transplantation. Conclusions Cautious antibiotic rechallenge can be successfully achieved without desensitisation in the majority of patients who have had non IgE mediated allergic phenomena to the same compound prior to transplantation. Idiopathic pulmonary fibrosis (IPF) is characterised by marked collagen deposition. The receptor subunit gp130 has been associated with the progression of fibrosis. The interleukin (IL)-6 family of cytokines all require gp130 to initiate signal transduction to activate either the extracellular regulated kinase (ERK) or signal transducer and activator of transcription (STAT) pathways. The IL-6 family of cytokines consist of IL-6, IL-11, oncostatin M (OSM), leukaemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), ciliary neurotrophic factor (CNTF), IL-27 and IL-31. Previous studies performed in our laboratory have demonstrated that exaggerated gp130-STAT3 signalling is fundamental to the development of bleomycin-induced lung fibrosis in a murine model. We hypothesise that pulmonary fibrosis is mediated by IL-6 family cytokine/gp130-STAT1/3 signalling. The aim of the current study was to identify which of the IL-6 family cytokines are important in the development of bleomycin-induced pulmonary fibrosis. Bleomycin or control saline was administered intranasally to individual IL-6 knockout (IL-6 -/-) mice and dual IL-6 and IL-11 a-receptor knockout (IL-6 -/-;IL-11aR -/-) mice. Collagen production was examined by histology and HPLC in lung tissue 30 days post treatment. No significant increase in collagen was observed in bleomycin treated IL-6 -/or IL-6 -/-;IL-11aR -/mice implicating a role for IL-6 in the development of pulmonary fibrosis. Interestingly, the histology of IL-6 -/-;IL-11aR -/mice displayed marked emphysema which was not observed in individual IL-6 -/mice suggesting this is an IL-11-mediated response. The role of IL-6 family cytokines in proliferation, myofibroblast differentiation and collagen expression were examined using fibroblasts isolated from wildtype (wt) and genetically engineered mice containing point mutations to prevent gp130-ERK1/2 signalling (gp130 757F ) or gp130-STAT1/3 signalling (gp130 STAT ). Overall, there was no significant increase in proliferation 48 hours post cytokine stimulation as assessed by WST-1 reagent. IL-6 and IL-11 did not stimulate a-SMA or collagen expression above control, measured by real time PCR. In conclusion, increasing evidence suggests that IL-6 plays an important role in the development of bleomycininduced pulmonary fibrosis but this does not appear to be induced by direct effects of IL-6 on fibroblast proliferation, differentiation or collagen production.

Mannose binding lectin (MBL) is a key mediator of innate immunity and efferocytosis (clearance of apoptotic cells) and is thus important in protecting against tissue damage. Reduced MBL is implicated in airways disease including infection, COPD and BOS, however, 'normal' plasma levels of MBL are highly variable due genetic polymorphisms complicating correlation with disease processes. We have previously shown reduced MBL and defective efferocytosis in BAL from patients with post-transplant BOS, but there are conflicting reports of the link between low plasma MBL levels, increased complement activation and graft rejection. To compare MBL levels in the peripheral blood and BAL compartments, we investigated MBL in paired plasma and BAL from 46 lung transplant recipients (10 stable; 32 stable with infection, 7 with lymphocytic bronchiolitis and 10 with BOS) and in plasma from 10 and BAL from 17 controls. In plasma, MBL levels were highly variable. No significant differences were noted among the transplant groups although levels were significantly reduced in all transplant patients vs. controls. There was no correlation between MBL and time post-transplant or pre-transplant diagnosis. In BAL, MBL levels were less variable and significantly reduced in patients with BOS (MBL ng/ml: Controls: 6.2 ± 1; stable 8.6 ± 3.8; stable infected 10.7 ± 2.7; BOS 2.2 ± 1.7). Interestingly, in all patients with LB, MBL levels were very low in both plasma (mean 35.8 ng/ml) and BAL (3 ng/ml). Low levels of MBL in the airway may play a role in reduced efferocytosis, leading to tissue damage and airways disease post-transplant. In normal subjects, external dead space with exercise is associated with a slower deeper breathing pattern compared at the same ventilation. With simulated lung restriction and constant intensity exercise, we tested the hypothesis that dead space combined with reduced exercise intensity to match ventilation, would alter pattern of breathing, reduce Inspiratory Reserve Volume (IRV) and thus increase dyspnea. Methods Eleven healthy male subjects, aged 28(8) (SD) years completed separate visits with (a) no restriction and (b) chest wall strapping to reduce FVC by 30 (7) Introduction Glossopharyngeal breathing (GPB) is used by competitive breath-hold divers to increase lung gas content above TLC to improve performance. This occurs by both lung expansion and gas compression. Whilst GPB is known to induce hypotension and tachycardia, little is known about the changes that occur to both the pulmonary circulation and the structural integrity of the thorax. The aim of this study was to investigate these changes within an elite cohort.

Methods Six male breath-hold divers were studied. Exhaled VC was measured before and after GPB. Subjects were studied in the supine position at baseline TLC and after maximal GPB above TLC at least 72 hours apart. Tc 99 m labelled macro aggregated albumin was injected and a computed tomography (CT) of the thorax was performed during breath-hold. Dynamic and single photon emission CT (SPECT) images were generated and analysed by two blinded Nuclear Medicine Physicians for perfusion intensity (Wilcoxon signed rank test) and dynamic regional blood flow. A paired t-test was used to assess physiological parameters. Registered CT images were used to determine structural change in the thorax.

Results Five subjects increased exhaled VC with GPB [mean (SD)] by 1.4 (0. 3) L (p < 0.001). There was a reduction in perfusion intensity following GPB in the anterior (p < 0.03) and inferior (p < 0.01) lung segments. There was no change in the timing of blood flow. 69% of the increase in expired lung volume above baseline TLC was via thoracic expansion (0.97 (0.3) L (p < 0.05)) with a caudal displacement of the diaphragm. One subject who was not proficient at GPB had no change in exhaled volume, CT appearance or lung perfusion. Background We have developed a sensitive method to determine conductance-lung volume (conductance profile) and distensibility-lung volume (distensibility profile) relationships using the forced oscillation technique (FOT). Using this method, we aimed to assess the effect of a short-acting bronchodilator (BD) on these profiles in asthma.

Methods Twenty two asthmatics and 20 healthy controls completed distensibility measurements (FOT) and lung function tests before and after BD. The conductance and distensibility profiles were described continuously and determined at specific lung volumes, residual volume (RV), FRC, TLC and midway between FRC and TLC (MID).

Results Following administration of BD: The conductance profile in the asthma group was shifted upwards, and the distensibility profile was altered such that significant increases in distensibility were observed at RV (p < 0.001) and FRC (p < 0.01), but not at MID or TLC. In contrast, no changes were seen in the conductance or distensibility profiles in the control group. Post-BD distensibility in asthma remained reduced compared to controls. Conclusion Using a sensitive method for determining conductance and distensibility profiles, we found that both conductance and distensibility are reduced in asthma across a range from low to high lung volumes. Both these profiles are altered in asthma after BD but not in controls. We propose that in asthma the remaining deficit in distensibility after BD will provide unique insight into to altered airway mechanical function due to airway remodelling. Cigarette smoke exposure is a major risk factor in susceptibility to serious respiratory infections, particularly in children. Although smoke exposure is known to alter immunity to infection, the underlying molecular mechanisms are not well understood.

Aim Identify regulatory mechanisms that drive impaired macrophage function.

Methods The MH-S alveolar macrophage cell line was exposed to a short 15 minute pulse of Cigarette Smoke Extract (CSE) prior to challenge with LPS or FITC-E.coli.

Results CSE blocked phagocytosis of E.coli and inhibited LPS activation of canonical and alternative TLR4 pathways. Both NFjB translocation and transactivation pathways were compromised as CSE inhibited IjBa degradation and p65 phosphorylation. CSE also blocked AP-1 activity by inhibiting p38, but not JNK or Erk1/2. We next excluded LPS tolerance mechanisms involving receptor internalisation or induction of negative regulators. As free radical species are abundant in CSE we investigated their role using the potent scavenger, reduced glutathione (GSH). Since GSH restored all responses, we screened a panel of oxidative/nitrosative stress markers and identified carbonylation as the only CSE inducible marker. Oxyblot analysis confirmed that CSE potently introduced carbonyl groups to many proteins (30-100 kDa range) in a dose and time dependent manner that inversely correlated with TNF-a expression. CSE treated macrophages also displayed heavily carbonylated pseudopodia that was reversed by GSH as determined by immunocytochemistry (ICC).

Conclusion Macrophage sensing and ingestion of pathogen is compromised by protein carbonylation of the outer membrane where phagocytic receptors cluster and also penetrates cytoplasmic regions where signalling moieties reside. Therefore, targeting single pathways will not restore macrophage function due to the global nature of CSE mediated carbonylation. Support NHMRC. Background Asthma shows varying levels of resistance to effective treatment by glucocorticoids. In studies on TGFb-induced epithelial mesenchymal cell transition (EMT) using the A549 type II human epithelial cell line, the regulatory effect of the glucocorticoid, dexamethasone (Dex, 0.1-1000 nM) on interleukin-1a (IL-1a)-induced interleukin-8 (IL-8) generation was markedly reduced in the presence of TGF-b 400 pM (n = 7; p < 0.05). Aim Our studies were designed to characterise the mechanism of the glucocorticoid resistance.

Results The resistance induced by TGF-b was: concentration dependent (4-400 pM); a glucocorticoid class effect as it also occurred with budesonide; independent of EMT: it was observed within 4 hours, whereas EMT requires 3 days; also observed in the central airway epithelial cell line, BEAS-2B and passaged, primary bronchial epithelial (NHBE) cells. Treatment of A549 cells with SB431542, a TGFb receptor type I kinase inhibitor, restored the Dex inhibitory effect on IL-8 release (from control 17 ± 7% to 45 ± 7%, inhibition in SB431542 1 lM, n = 9; p < 0.05). In A549 cells transfected with a glucocorticoid response element (GRE)-driven reporter gene, TGFb (40 pM) inhibited the GRE response to Dex (0.1-1000 nM) by more than 80%. In addition, TGF-b impaired Dex regulation of the GRE-dependent gene, IjB. PGE2 plays a protective role in asthma by inhibiting airway inflammation. It is predominantly produced by epithelial cells in response to pro-inflammatory stimuli and acts as an autocrine and paracrine mediator. Prostanoids have been shown to regulate expression of enzymes involved in their metabolism, as well as expression of their receptors and that regulation is tissue-and cell-specific. Despite its importance, however, mechanisms underlying the regulation of expression of enzymes involved in PGE2 metabolism and its receptors in human lung epithelial cells have remained elusive. Therefore, we hypothesised that PGE2 regulates expression of PGE2 synthase 1 (PGES1) and its receptors (E Prostanoid (EP) 1-4) in human airway epithelial cells.

Methods Real Time RT PCR and FACS analysis were used to assess mRNA and protein expression, respectively in human airway epithelial cells 16 HBE before and after PGE2 stimulation.

Results PGE2 up-regulates PGES1 in time and concentration dependant manner. In addition, EP receptors (EP1, EP2 and EP4) were up-regulated following PGE2 stimulation at mRNA level. However, these receptors show different dynamics in expression. While EP1 reaches peak in mRNA expression at 6 hour, peak expression for EP2 and EP4 is at 12 hour post stimulation. Monocyte derived Dendritic Cells (DCs) have been recognised for their potential role in immune responses and their functional relevance with regard to adaptive immune responses although more detailed knowledge of DC biology in human airways is required. The objective of this study was to modify the monocyte derived DCs from peripheral blood and direct the cells via exposure to pro-inflammatory conditions as seen in COPD, with a view to identifying novel targets for cellular therapy. We characterised monocyte-derived DCs in culture and evaluated the effects of human rhinovirus infected bronchial epithelial cells, pI:C (polyinosine-polycytidytic acid) and BC (bacterial extract) on directing DC differentiation and maturation in culture. We found an impaired adaptive immune response, and in particular, an impaired CD8 effector cell function in COPD patients. Our DC culture results showed that both MHC-I and MHC-II expression on DCs from COPD were significantly down regulated compare to healthy controls, which could affect MHC restricted Ag presentation, and lead to a failure to activate responder T cells. Furthermore, we tested the capability of monocyte-precursors to differentiate into functional DCs. Only a very small percentage of cultured monocytes from patients with COPD was capable of differentiating into mature DCs, compared with healthy controls. During DC activation, there was up-regulation of co-stimulatory (CD80/86) and maturation markers (MHCs), enabling DC to activate naïve T cells in mixed lymphocyte culture both in COPD patients and healthy controls. Our preliminary data indicated that this activation leads to the generation of effector T cells, further study is needed. Defective DC activation of T cells may underlie poor T cell responsiveness in COPD in response to inflammation and may, in part, determine the response to therapy. Our data suggest a promising role in vitro for pharmacologic treatment as a means of generating functional DCs and will further stimulate speculation regarding their potential clinical application. Support NHMRC Australia. Anxiety and depression are the two most common and the least treated comorbidities associated with Chronic Obstructive Pulmonary Disease (COPD). They have been found to have a statistically significant and independent adverse association with mortality, longer length of hospital stay, persistent smoking and worse physical and social function. Evidence for various interventions to overcome these symptoms in COPD is limited or inconclusive.

Methods This is a Cochrane review. All randomised controlled trials (RCTs) and cross over trials (COTs) dealing with pharmacological and/or psychological interventions for anxiety and/or depression in adults with COPD were considered. Search was performed via various medical search engines and Cochrane database register. Duration of follow-up in the studies was generalised as short-term (0-3 months), medium-term (3-6 months) and long-term (6-12 months). The data was analysed using the fixed effect model and difference in symptom control by interventions as mean difference (MD) or the standardised mean difference (SMD) depending upon the heterogeneity of various scales used.

Results Eight RCTs/COTs were included. Pharmacotherapy showed nil significant effect to control anxiety (SMD of -0.33, p value 0.16, n = 76), however, showed significant benefit in controlling depression symptoms (SMD -0.57, p value 0.02, n = 76) in COPD over short-term. On the other hand, CBT was found to be beneficial in controlling both anxiety (MD -5.0, p value 0.04, n = 30) as well as depression (MD -7.30, p value 0.02, n = 30) in COPD over short term.

Conclusion CBT is superior as compared to pharmacotherapy over short-term to control anxiety and depression in COPD. Background The emergence of clonal Pa and associated risk of cross-infection is a major cause for concern in CF centres in several countries, including Australia. Two clonal Pa strains (AES1 and AES2) have been detected in several eastern Australian CF centres, but the overall prevalence of these and other strains throughout Australia remains unknown.

Methods A cross-sectional study involving 18 CF centres (8 paediatric, 9 adult, 1 combined) was performed. In total, 838 sputum-producing children and adults with documented Pa infection provided two sputum samples, 6 months apart, and 3 Pa isolates from each sample were genotyped by repPCR-based cluster analysis.

Results Collectively, AES1 and/or AES2 strains were identified in 44% of Pa infected CF patients and found in all participating CF centres. Several other minor clonal strains were also identified in many centres. Only 25% of patients were infected with unique (non-clonal) Pa strains and 8% of patients were infected with more than one clonal strain.

Conclusion Clonal Pa strains are common in Australian patients with CF. There is marked variation in prevalence of both major and minor clonal strains between CF centres and within states. Longitudinal analysis of the clinical impact of clonal Pa infection is urgently required so as to allow an evidence-based approach to patient management and infection control. Reduced glutathione (GSH), a major component of anti-oxidant defence, is transported into the lung via CFTR. GSH protects against Myeloperoxidase (MPO)-induced oxidative stress by undergoing oxidation to GSSG and GSA. Excess MPO induces chlorination of tyrosine (3-CL-Tyr) via the production of hypochlorous acid. We undertook a cross-sectional survey of young children with CF participating in our early surveillance program that includes annual bronchoalveolar lavage (BAL) and chest CT scan. Markers of neutrophilic inflammation and of the GSH system were determined in BAL and the presence of bronchiectasis (B) and air trapping (AT) determined on chest CT. 188 samples from children with CF (mean age 3.35 years) and nine samples from children without CF (mean age 6.13 years) undergoing investigation for chronic respiratory symptoms (NCF) were studied. CF samples had more neutrophils that NCF samples (geometric mean 42.6 vs.

3.0 · 10 3 /ml fluid retrieved), more MPO (239.4 vs. 0.31 ng/ml, p < 0.001), lower levels of GSH (1393.7 vs. 3285.1 nM, p < 0.001) and a trend for a lower GSH:GSSG (46.2 vs. 95.2, p = 0.07). Within the CF samples levels of MPO correlated with GSSG (p = 0.01), and GSA (p < 0.001) and 3-Cl-Try correlated with GSSG (p = 0.005) and GSA (p < 0.001) indicating neutrophilic inflammation exceeding anti-oxidant defence capability. However, after controlling for age and the presence of free neutrophil elastase, there were no relationships between GSH, GSSG or GSA and either B or AT. While our data demonstrate GSH deficiency and defective anti-oxidant defence, these are not related to structural lung disease. Longitudinal studies will be required to determine the impact of GSH deficiency in the initiation and progression of lung disease in CF. Support CFFT, Inc (USA); NHMRC, ACFRT, MCRI and PMH Foundation (Aust).

Introduction There are no Australasian guidelines for the detection and eradication of Pseudomonas aeruginosa in preschool children with CF. The optimal eradication regimen for preschool children remains uncertain. Aims To develop Australasian guidelines for P. aeruginosa detection and eradication in preschool children with CF based on a national multi-centre randomized control trial.

Methods An electronic web-based questionnaire was sent to every tertiary paediatric CF centre in Australasia to determine current detection and eradication practices. Results All eleven centres completed the survey. A combination of positive oropharyngeal culture (OPC) and confirmatory bronchoalveolar lavage (BAL) culture was the most common method of P. aeruginosa detection (55%), with surveillance frequencies varying; annually (n = 3, 27%), every clinic visit (3, 27%) and clinically indicated (4, 36.4%). Eradication treatment was instigated on one positive culture (OPC n = 5, BAL culture n = 5 centres) for P. aeruginosa at any bacterial density (50%) or bacterial density ‡105 cfu/ml (40% of centres). Eradication regimens varied between centres with most (81%) using intravenous antibiotics either alone (n = -1); in combination with 3-12 months nebulised antibiotics (n = 3); or with 1-3 months nebulised and oral antibiotics (n = 5). Choice of regimen was influenced by clinical status in three centres. Two centres used combinations of inhaled and oral antibiotics alone. Failure to eradicate resulted in a change in treatment in 64% of centres. Inhaled tobramycin 80 mg (28 days and 12 months) was considered the least acceptable regimen for preschool children in terms of efficacy and burden of care with most favouring more aggressive IV treatments.

Conclusion This survey supports a call for evidenced based Australasian guidelines for the detection and eradication of P. aeruginosa in preschool children. Comparative trials of the most favoured eradication regimens would enhance this process. Pseudomonas aeruginosa is the most important respiratory pathogen in cystic fibrosis (CF). Although unproven, it is generally thought to be acquired from the environment. However, molecular typing studies indicate person-to-person transmission by some clonal strains may also occur. Clonal P.aeruginosa strains have not been compared previously with isolates collected from non-CF patients, animals or the environment. Aim To determine sequence-based clonality of P.aeruginosa isolates collected from several different ecological niches.

Methods MLST and sequence type (ST) analysis was performed on 519 isolates collected from CF patients (n = 216), non-CF patients (n = 116), animals (n = 107), and the natural environment (n = 80). CF isolates included each of the major and minor clonal Australian strains and a range of unique strains isolated from patients residing in SE Qld. Non-CF, animal and environmental isolates were collected from the same region.

Results Of the 282 individual strains detected, 51 (18.1%) were found in more than one niche. Overall, 29 unique and minor clonal CF strains were detected in at least one other niche; including 10 CF strains found in the environment. To date, none of the three major Qld CF clonal strains have been detected in another niche.

Conclusions In CF, environmental exposure to P aeruginosa seems important for acquiring unique and minor clonal strains. Finding that the three major clonal strains were confined to CF patients further suggests person-to-person transmission is occurring and/or strain associated adaptation to the CF lung. Support NHMRC, ACFRT, TPCH Foundation. Background Clostridium difficile colitis remains a rare but potentially life threatening complication in CF patients particularly in the post lung transplant setting.

Aim (1) To review the incidence of C. difficile colitis among non-transplant and post-lung transplant CF patients attending our centre.

(2) To identify the clinical features in CF patients presenting with CDAD. Method Retrospective study on C. difficile toxin status in all fecal samples collected in CF patients between 2000 to 2009 was reviewed. Patients with positive C. difficile toxin were identified as index cases, those with negative samples were selected as control cases.

Results Two hundred and twenty-three fecal samples were collected from 74 CF patients. Nineteen CDAD cases were identified in 15 patients including 13 non-transplant and two post-transplant patients. Thirteen had mild colitis and two had fulminant colitis. Incidence density of CDAD in non-transplanted CF patients (2.8/100 000 patient-days) is comparable to the transplanted group (two episodes/ 100 000 patient-days). Time to diagnose CDAD among post-transplant patients is shorter than non-transplant patients (1 vs. 6 days). A significantly proportion in the CDAD group had recent Ciprofloxacin when comparied to controls ( 38.5% vs. 0 %, p-value: 0.0006.). A significantly higher proportion of patients in the CDAD group are currently on gastric suppression therapy than control (92% vs. 59%, p-value: 0.03).

Conclusion The incidence density of CDAD is comparable between pre and post transplant CF patients. CDAD is more common among patients with prolonged Ciprofloxacin treatment and concurrent gastric acid suppression. Improving patient awareness by optimising patient education particularly during prescription of Ciprofloxacin or gastric acid suppression treatment can prompt early presentation and management of CDAD.

Conflict of Interest No.

G KARMAKAR 1 , D MILNE 2 , M WILSHER 1 1 Green Lane Respiratory Services, and 2 Department of Radiology, Auckland City Hospital, Auckland, New Zealand Introduction Major (massive or submissive) pulmonary embolism (PE) is a potentially lethal condition particularly if associated with cardiogenic shock. Thrombolysis is accepted as standard treatment for massive PE with hypotension, but it carries substantial risk of bleeding and risk may outweigh the benefit in sub-massive PE. The objective of this study was to examine risk factors for and the outcome of major PE in this institution.

Methods We collected data retrospectively from all patients with MPE requiring ICU admission in Auckland City Hospital (ACH) over a 5 year period. The primary outcome variable was mortality with secondary variables including precipitating factors and morbidity.

Results Twenty-eight subjects (12 massive PE) were identified. Eight of 12 with massive PE were thrombolysed and four were treated conservatively with 30 day mortality of 50% and 25% respectively. Twelve of 16 patients with sub-massive PE received thrombolysis with no mortality. Significant bleeding complications were reported in four of 20 thrombolysed patients. Prior surgery without DVT prophylaxis was identified as a precipitant in 10 patients.

Conclusions Massive PE carries significant mortality irrespective of thrombolysis but such treatment appears safe in sub-massive PE. In spite of evidence of efficacy, failure to offer prophylaxis of DVT in the perioperative setting appears an ongoing risk factor for major PE. Introduction There is a need to improve general understanding of the epidemiology, pathophysiology, outcome and therapies for rare (orphan) lung diseases. Aims 1) To establish an electronic reporting registry of orphan lung diseases in Australasia. 2) To provide a useful resource for physicians and patients.

Methods A website (www.arnold.org.au) was developed containing information on 30 orphan lung diseases, useful links and an on-line patient discussion forum. TSANZ members were invited to participate in reporting cases electronically by a quarterly email reminder. The following data were entered: first two letters of given and family name, date of birth, postcode and whether the patient was new or old to the physician.

Results Ethical approval in New Zealand is still awaited. Results Twenty-three H1N1 cases of mean ± SD age 41.7 ± 7 years were confirmed from 826 known LT recipients (incidence 2.8%). Cases peaked in New South Wales (n = 10) and Queensland (n = 6) consistent with epidemiology in the general community. Clinical manifestations included allograft dysfunction in 17 of 23 (73.9%), upper respiratory tract symptoms only 26.1%, fever 52.6%, myalgias 68.4%, hypoxia 26.3% and radiological infiltrates 42.1%. Mean hospitalisation was 11 ± 9.1 days. Cases were diagnosed in the hospital setting (n = 16) and in the community (n = 7). Other risk factors included obesity n = 7, diabetes n = 4 and malignancy n = 3. Treatment consisted of oseltamivir 75 mg bd initially for 5 days in all 23 cases, extension beyond 5 days n = 14 (mean 8 ± 1.4 days) due to ongoing symptoms, steroid therapy n = 17, mechanical ventilation n = 1 and noninvasive support n = 2.5 patients (21.7%) have not returned to baseline lung function and there were four deaths (BOS grade three n = 3 and grade 0 n = 1 prior to diagnosis).

Conclusions The incidence of H1N1 in the Australian LT population was less than that estimated for the broader community but mirrored the geographical distribution. The majority experienced allograft dysfunction with most deaths recorded in those with preexisting BOS grade 3. We recommend H1N1 vaccine (Panvax, CSL) for all LT recipients. As the only commonly transplanted organ exposed to the atmosphere, the lung allograft may be uniquely susceptible to IgA deficiency. Since IgG deficiency is common after transplantation, we hypothesised that IgA production may be similarly affected and may contribute to BOS pathogenesis.

Methods We conducted a cross-sectional evaluation of our transplant cohort. Total IgA, IgM, IgG, and IgG subclasses were measured in serum using ELISA. Demographic data, immunosuppression and BOS status were recorded.

Results One hundred and twenty three patients (85% of the total cohort, aged 43.7 years (range 13.6-64.9), 49% female, 39% CF, 39% COPD) were evaluated. The median IgA level was 1.5 g/l (normal range 1-4 g/l). 33 patients (27%) were IgA deficient, and 7 (6%) of these were pan-hypogammaglobulinaemic. IgA levels were lower in patients with BOS (median, IQ range; 1.1, 0.8-1.7 vs. 1.6, 1.0-2.2, p = 0.006). IgA deficiency was not associated with age, sex, diagnosis, transplant type or time post-transplant. The median IgG level was 7.6 g/l (normal range 7-16 g/l) and 52 patients (42%) were deficient. IgG levels were lower in BOS (median, IQ range; 6.6, 5.6-8.0 vs. 8.6, 6.3-10.5, p = 0.002) and IgG deficiency was more common in COPD (60%, p = 0.01). IgG levels were negatively correlated with age (r 2 = 0.20, p = 0.03). Multivariate logistic regression models identified IgA deficiency as independently associated with BOS (p = 0.04), while the association of IgG deficiency with BOS was explained by interaction between BOS, age and COPD. IgM deficiency was present in 17 patients (14%) and was more common in males (76%, p < 0.01), but was not significantly different in BOS. IgG, IgA and IgM levels were not associated with immunosuppression or the use of basiliximab induction Conclusions Serum IgA deficiency is common after transplantation and is independently associated with BOS. Impaired defence of mucosal surfaces because of IgA deficiency may contribute to BOS pathogenesis. Results RV infection alone led to induction of, pSTAT-1, CXCL10 and release of IFN-k siRNA, knockdown of MDA-5 reduced CXCL10, IFN-b and pSTAT-1 and also reduced IFN-k. Silencing of TLR-3 and RIG-I alone had no effect. When combined both siRNA for TLR-3 and MDA-5 had no additional effect. Treatment of BECs with BX795 inhibited the production of Type I IFN but only partially inhibited IFN-k release. Blockade of p38MAPK however led to substantial blocking of IFN-k release and also led to a marked reduction in the typeIIFN response.

Conclusion We found that following infection with RV, BECs Type I IFN responses, pSTAT-1 induction as well as release of IFN-k was dependent on MDA-5. Blockade of TBK-1/IKK by BX795 reduced Type I IFN response, but IFN-k release was only partially inhibited Blockade of p38MAPK resulted in suppression of both IFN-k and type IFN, suggesting this pathway is crucial in the antiviral response to RV infection.

Conflict of Interest None.

Introduction Pregnant women have increased susceptibility to respiratory virus infection. Human rhinovirus (HRV) and influenza are the most common respiratory viruses isolated during severe exacerbations in pregnant asthmatics and are high risk factor for respiratory-related maternal and neonatal morbidity and mortality. Understanding the innate and adaptive immunological processes underlying respiratory virus infection in pregnancy will lead to improved treatments, resulting in better health outcomes for both mother and baby.

Methods Cross-sectional study of 12 pregnant asthmatics, 10 pregnant non-asthmatics, 8 non-pregnant asthmatics and 10 healthy non-pregnant women. Blood mononuclear cells were cultured with HRV (RV43 or RV1B), influenza A (H3N2), phytohaemagglutinin or TLR3 and TLR7 agonists, polyinosinic:polycytidylic acid and Imiquimod, respectively. Protein concentrations of IFN-a, IFN-k IFN-c, IL-10 and IL-17 were quantified from culture supernatant by ELISA and CBA.

Results Pregnant asthmatics had significantly increased IL-17A and IL-10 (median 19.3 pg/ml and 258.5 pg/ml, respectively) compared to healthy women (median 0 pg/ml and 27.5 pg/ml, respectively, p < 0.004). IFN-c was significantly reduced in pregnant asthmatics (median 721.8 pg/ml) compared to healthy women (174.3 pg/ml, p = 0.003). IFN-a and IFN-k were induced by HRV and influenza In response to RV43, pregnant women had decreased IFN-a production (206.5 pg/ml) compared to healthy controls (460.8 pg/ml, p = 0.002) whilst IFN-k production was significantly reduced in both pregnant asthmatics (25.7 pg/ml, p = 0.001) and pregnant non-asthmatics (0 pg/ml p < 0.0001).

Conclusion Increased IL-10 and IL-17 production and reduced IFN-c, IFN-a and IFN-k are important inflammatory and anti-viral alterations during pregnancy and asthma; providing important insight into why pregnant women are more susceptible to respiratory virus infections. Support NHMRC.

Conflict of Interest No. Nomination Nil.

The incidence of NTMLD is increasing markedly in Australia. It is not known why patients with NTMLD are susceptible to these organisms, as most patients do not have identifiable risk factors or a documented immune defect. As cell-mediated immunity is crucial for control of mycobacterial disease, we assessed whether NTMLD is associated with diminished Th1 immune responses. Methods Our study cohort consisted of 27 patients with NTMLD at different stages of treatment, 15 offspring of 12 patients and 21 unrelated healthy controls. Plasma levels of CXCL10 and IL-18 were assayed on all subjects by Cytometric Bead Array or ELISA. In a subset of subjects, PBMC were assessed for production of IFNg, IL-5, IL-17 and IL-10 in response to stimulation with mitogen (SEB) and purified protein derivative (PPD). All data was analysed using non-parametric statistical tests.

Results Plasma levels of both CXCL10 and IL-18 were higher in NTM patients compared with unrelated controls and/or offspring (p < 0.001). CXCL10 levels were lower in patients who responded well to treatment compared to those who responded poorly (p = 0.03). Compared with healthy controls, PBMC from NTM patients produced similar levels of IFNg, IL-5 and IL-10, less IL-17 (p < 0.05) in response to SEB, but more IL-10 in response to PPD (p < 0.01).

Conclusions NTMLD is not associated with diminished Th1 responses. Elevated levels of CXCL10 indicate ongoing IFNg release in vivo. NTM patients may have a bias towards IL-10 production in response to mycobacterial antigens and/or harbour an intrinsic defect in Th17 immunity. Paracetamol is commonly used in infants as an analgesic and antipyretic. Cross sectional studies have reported an association between frequent paracetamol consumption in early life and risk of childhood asthma. To date, no study has controlled for indication for use of paracetamol, or confounders such as history of respiratory infections, which is independently associated with asthma. Aim To examine, in a prospective cohort study, whether frequent paracetamol exposure during early life increases the risk of childhood asthma.

Method Six hundred and twenty infants with an atopic family history were recruited. Paracetamol exposure was prospectively documented on 18 occasions to 2 years of age, including the number of days and the indication for use. An interviewer-administered questionnaire was used at 6 and 7 years to ascertain asthma in the previous 12 months.

Results Exposure to paracetamol occurred in 97% of participants by two years of age. Increasing frequency of use of paracetamol was associated with increased risk of childhood asthma (OR = 1.18, 95%CI 1.00-1.39 per doubling of days of use). Adjustment for frequency of respiratory infections substantially reduced the strength of these associations (aOR = 1.08, 0.91-1.29). Paracetamol use for non-respiratory tract infections and injury was not associated with asthma (OR = 0.95, 0.81-1.12).

Conclusions In children with a family history of allergic disease, we found no association between early paracetamol use and risk of subsequent allergic disease when adjusted for respiratory infections, or when only paracetamol use for non-respiratory tract infections was examined. These findings do not support suggestions that paracetamol use up to age two years increases the risk of asthma. Support NHMRC. Aim To determine whether a water-based exercise program was effective in improving exercise capacity and quality of life in people with COPD with physical co-morbidities compared to a land-based exercise program or no exercise.

Methods Participants with COPD referred to pulmonary rehabilitation and who had a physical co-morbidity were randomly allocated to one of three groups: land-based exercise, water-based exercise or a control group of no exercise. The two exercise groups trained for eight weeks, three exercise sessions per week. Participants underwent measurements of respiratory function, exercise capacity and quality of life by a blinded investigator at baseline and following intervention.

Results Of 53 participants (mean (SD) age 72 (9) Knowledge of airway dimensions is critical for bronchoscopists assessing airway stenoses requiring interventions. It is also important for evaluating phenotypic features of obstructive lung diseases (OLD). However, real-time quantification of airway dimensions during bronchoscopy is lacking. Inserted into the airways via a bronchoscope, anatomical optical coherence tomography (aOCT) is a light-based imaging technique with the unique capacity to obtain such measurements. We describe the validation, research and clinical applications of bronchoscopic aOCT. Methods (Study 1) aOCT was validated in a phantom model, excised porcine airways and in 4 human subjects. (Study 2) Airway compliance curves were constructed and compared from aOCT-based measurements in volunteers with and without OLD during bronchoscopy. (Study 3) Stenosis dimensions (length, calibre) were measured compared in patients with symptomatic airway stenosis using pre-procedure computed tomography (CT) and intra-procedure aOCT (Bland Altman analysis) to determine interventional strategy.

Results In phantom and porcine airways, aOCT measurements were accurate and reliable. Mean CT-aOCT diameter measurements differed by 0.4 ± 1.3 mm.

(2) Airway compliance was increased in COPD (n = 9) relative to control (n = 10) and asthma (16) subjects, which were similar. (3) In 14 patients, the mean difference between CT and aOCT-based stenosis measurements was 0.4 ± 8.6 mm. aOCT proved more reliable when CT image quality was poor or where a delay occurred between CT and bronchoscopy.

Conclusions aOCT provides real-time measurements of airway dimensions which are accurate and reliable and can be used for research and clinical applications. Nomination Ann Woolcock Young Investigator Award. Support NHMRC. Disclosure to declare Yes.

A notable feature of allergic asthma is the infiltration of mast cells into human airway smooth muscle (hASM) bundles. Thus, mast cells and hASM can likely exhibit mutual functional modulation via direct cell-cell contact or through released factors. To examine this possibility, we have used a human mast cell line (HMC-1) to evaluate mast cell modulation of hASM cell function.

Methods HMC-1 cells were transfected with human FcRIa, and FcRI expressing cells were flow sorted. The functional activity of these cells (HMC-1a) was examined by measurement of released cytokines via IgE/antigen stimulation. hASM cells were co-cultured with HMC-1a cells, or with conditioned media derived from HMC-1a cells, to examine the impact on cytokine release.

Methods HMC-1a cells were activated by IgE/antigen to release IL-8. The co-culture of hASM cells with HMC-1a cells, induced both IL-8 (n = 5, P < 0.05) and eotaxin (n = 5, P < 0.001) production from hASM cells and this effect was greatly amplified when HMC-1a cells were antigen-activated. The effect of HMC-1a co-culture could be reproduced by addition of conditioned media derived from activated HMC-1a cells. A Bio-PlexÔ cytokine array showed release of MCP-1 and MIP-1b was strongly induced from HMC-1a cells upon IgE/antigen stimulation. However, treatment of hASM cells with these cytokines did not elicit IL-8 release.

Conclusions Our study provides further evidence that the release of soluble mediators from activated mast cells can induce cytokine production from hASM cells. Further work is currently ongoing to identify the factor/s responsible for this effect. We have previously demonstrated that gp130-mediated STAT3 signaling is required for bleomycin-induced lung fibrosis in mice. To determine the role of phosphorylated STAT3 (pSTAT3) in the development of human lung fibrosis we examined STAT3 and the regulation of STAT3 expression in lung tissue from idiopathic pulmonary fibrosis (IPF) patients. Immunohistochemistry revealed nuclear localization of pSTAT3 in fibroblastic cells within fibrotic foci. Suppressor of Cytokine Signaling-3 (SOCS3) is a known negative regulator of gp130-induced STAT3 activation. We tested the hypothesis that reduced SOCS3 expression may account for elevated pSTAT3 in cells within the fibroblastic foci of IPF lungs. RT 2 PCR Profiler analysis of the JAK/STAT pathway demonstrated that IL-6 up-regulated SOCS3 mRNA in both IPF and HLF. Western blot analysis confirmed that SOCS3 expression was not aberrant in these cells, although a trend towards reduced SOCS3 expression was evident. Our analysis identified six JAK-STAT pathway associated genes that were significantly altered in IPF cells following IL-6 exposure for 30 minutes but of those, only IL-20 was up-regulated. Examination of other known regulators of STAT signaling including SOCS1, SOCS2, SOCS4, SOCS5, PIAS1, PIAS3 and protein tyrosine phosphatase non-receptor type 1 (PTPN1) was performed but only SOCS1 expression was reduced in IPF. In summary, dysregulation of SOCS3 does not appear to cause high STAT3 levels in IPF tissue but the potential regulation by SOCS1 is the subject of ongoing investigations. The phosphoinositide 3 kinase (PI3K) signal transduction pathway contributes to the airway remodelling associated with asthma; however, the precise roles of the specific PI3K isoforms are currently unknown. In this study, we investigated the roles of the class IA PI3K isoforms p110a, p110b and p110d in airway smooth muscle (ASM) cells derived from asthmatic subjects and ASM cells and lung fibroblasts from non-asthmatic subjects.

Methods Cells were stimulated with transforming growth factorb (TGFb; 1 ng/ml) and/or 10% FBS in the presence or absence of specific PI3K inhibitors PIK75 (p110a), TGX221 (p110b) or IC87114 (p110d) (all 0.01-1 lM) or vehicle control (DMSO). Fibronectin deposition, VEGF and IL-6 secretion were measured using ELISA, mitochondrial activity was assessed by MTT assay and proliferation by Bromodeoxyuridine (BrdU) incorporation assay.

Results In non-asthmatic ASM cells inhibition of p110a and p110b decreased VEGF and IL-6 secretion and cell proliferation (n = 11; p < 0.05), whereas in asthmatic ASM cells, only inhibition of p110a (n = 4-6, p < 0.05) but not p110b (n = 4-6, p > 0.05) had an effect. Furthermore, we demonstrated isoform specific roles with p110a (n = 4, p < 0.05) but not p110b (n = 3-4) or p110d (n = 3-5) modulating fibronectin deposition in ASM cells and lung fibroblasts.

Conclusion Specific PI3K isoforms have distinct roles in the regulation of inflammatory cytokines (IL-6), growth factors (VEGF) and extracellular matrix proteins (fibronectin) associated with airway remodelling. Intrinsic differences exist in the roles of the PI3K isoforms in asthmatic ASM. Acute Respiratory Distress Syndrome is characterized by inflammation and fibrosis. Cellular therapies potentially restore pneumocytes and reduce inflammation. Aims We evaluated the role of term human umbilical cord mesenchymal stem cells derived from Wharton's jelly (uMSCs) and Human Amnion Epithelial Cells (HAECs) in treating a Bleomycin-induced model of lung injury. Methods Cells were administered systemically into a mouse model of acute lung injury 24 hours following intra-nasal administered Bleomycin.

Results Both HAECS and UMSCs reduced inflammation with decreased TNF-a, IL-1, IL-6 and TGF-b. Collagen in the lung was significantly reduced by both uMSCs and hAECs as a possible consequence of increased degradation by matrix metalloproteinase-2 (MMP-2) and down-regulation of their endogenous inhibitors the tissue inhibitors of matrix metalloproteinases (TIMPs) -1 and -2. uMSCs were detected in the lung at 2 weeks postinjection, vs. 4 weeks for hAECs. In addition, uMSCs did not demonstrate lung differentiation while hAECS developed an alveolar phenotype.

Conclusions Both uMSCs and hAECs, have anti-inflammatory properties and reduce fibrosis in lung injury but hAECs adopt a lung phenotype Support Small Grant Monash University. Nomination Nil.

Background With improvement in clinical care and longer survival of patients with cystic fibrosis, pregnancy has become commonplace. However the impact of cystic fibrosis on maternal health and foetal outcomes requires ongoing review.

Methods A retrospective study of 20 pregnancies from 18 women with cystic fibrosis during the period 1995-2009 was performed. Changes in lung function, body mass index, and development of gestational diabetes were recorded. Foetal outcomes and maternal survival were examined and the influence of pre-pregnancy parameters on outcomes were evaluated.

Results Mean age of pregnancy was 29.1 years with a mean pre-pregnancy FEV1 of 65.6% predicted. Eleven out of twenty pregnancies had a pre-pregnancy FEV1 <60% predicted. During pregnancy, FEV1 fell by 4.76% (CI 1.59-7.92), but recovered to baseline within 6 months post-partum. Mothers gained a mean weight of 7.6 kg and gestational diabetes developed in 42.9% of women. All women delivered live births apart from one therapeutic abortion. Five infants were preterm and three had low birthweight for age. Four mothers either died or required lung transplantation after pregnancy on follow up. FEV1 <60% predicted and body mass index <20 kg/m 2 were significant predictors of foetal complications. Background Carrier screening for CF has been available for many years but there is no national program for population-based screening in Australia. Knowledge of Australian CF healthcare professionals' attitudes towards carrier screening would provide useful information about how a program could be implemented. The aim of this study was to investigate the attitudes of CF respiratory physicians and CF clinic coordinators in Australia towards population-based carrier screening for CF. Method A purposed designed questionnaire assessing knowledge and attitudes towards CF carrier screening was distributed to respiratory physicians and CF clinic coordinators throughout Australia. Results There were 111 respiratory physicians registered with the CF special interest group of TSANZ and 30 CF clinic nurses identified through the CF coordinators network. Seventy-five responded, 55 respiratory physicians (49.5%) and 20 coordinators (67%). Forty-two (56%) respondents were in favour of population-based carrier screening for CF. Sixty-four (85%) rated raising a child with CF as difficult/very difficult, 63 (84%) rated the shortened life span as a significant concern and 64 (85%) the daily treatment regimen as a significant concern. Disadvantages of screening were perceived anxiety amongst carriers (n = 65, 87%) and discrimination of carriers (n = 42, 56%). Respondents rated the following barriers as most important: limitations of predicting clinical outcomes (n = 47, 65%) and insufficient time and resources for providers (n = 45, 61%). Fifty-four (76%) of respondents believed they had a role in the development of a CF carrier screening program. Adherence to medication regimens in patients with cystic fibrosis (CF) vary substantially. Direct measures of adherence using electronic monitors attached to medication bottles enable the precise recording of usage. The macrolide antibiotic, azithromycin has demonstrated clinical benefit when used in CF patients with moderate to severe impairment of lung function. Aim This study compares the adherence levels of CF patients randomised to two different treatment regimens of azithromycin, measured by electronic monitoring. Methods Patients were prescribed the medication once (1000 mg) or three times (500 mg) a week. Data were collected over 24 weeks using electronic monitoring devices. Adherence measures were defined as: Total adherence (total amount of medication taken divided by total medication prescribed) and total number of days adhered (number of days where prescribed doses were taken divided by number of days monitored).

Results The study recruited 51 participants (57% male; mean age = 33.7 SD = 8 years, mean FEV1 % = 62.2, SD = 22.8). Total adherence in patients prescribed the weekly regimen (M = 100.19, SD = 6.3%) were significantly different compared to the three times a week regimen (M = 89.4, SD = 17.2%, p < 0.05). No significant difference was observed in total number of days adhered. FEV1% predicted negatively correlated with adherence to medication (total adherence r 2 = -0.28, p<0.05, days adhered r 2 = -0.29, p < 0.04) and to BMI (r 2 = 0.35 ,p < 0.01). Positive correlation was observed between age of the participant and adherence to medication (total adherence r 2 = 0.31, p < 0.01, days adhered r 2 = 0.41, p < 0.01).

Conclusion Participants adhered better to a once weekly regimen than a three times a week regimen. Preclinical studies in non-human primates (NHP) are essential to estimate effectiveness and safety in developing gene transfer protocols to treat cystic fibrosis (CF) airway disease prior to clinical trials. Lentiviral (LV) vectors can provide in vivo gene expression and persistence suited to long lasting CF airway correction 1 in mice. We have begun examination of LV gene transfer in lungs of marmosets (Callithrix jacchus), a small non-human primate with lung anatomy and physiology similar to humans. Methods Lysophosphatidylcholine (LPC, 0.1%) pre-treatment was followed by a LV vector encoding the lacZ (LV-lacZ) reporter gene, pseudotyped with the VSV-G surface protein. Doses were delivered into the trachea of four intubated marmosets. Trachea and lungs in two animals were examined after 1 week; blood taken daily was tested for presence of vector particles.

Results Epithelial cell lacZ gene expression was present primarily in conducting airways in a patchy distribution. A transient O2 desaturation was noted in some animals after LPC administration; behavioural and physiological indices were normal postoperatively. Limited patches of haemorrhage and neutrophil / mononuclear cell infiltration were deemed unremarkable by a veterinary pathologist. Serum p24 LV capsid protein levels that appeared after dosing were absent after day two.

Conclusions These first studies indicate LPC/LV dosing procedures are well tolerated and can induce target-cell gene expression. Further histological and immunological analyses are in progress. The remaining two animals will undergo longer-term assessment of the success of lentiviral lung gene transfer.

Background Bronchiectasis and air trapping are important features of cystic fibrosis (CF) structural lung damage, however data on disease progression in young children are lacking. Aim To assess longitudinal changes in CT-detected early structural lung damage in.

Methods Subjects included 117 children (age range 0.2 to 6.9 years) who underwent 327 annual CT scans, with 210 paired scans. Each CT scan consisted of three slices at endinspiration and three slices at end-expiration. The left and right upper, middle and lower zones were assessed for the presence and extent (none, less than 50%, more than 50%) of bronchiectasis and air trapping using previously described methods. Infection and inflammation were assessed using bronchoalveolar lavage at the time of CT scan.

Results Bronchiectasis was present in 37% of initial scans, persisting in 75% of subsequent scans. Median extent increased from initial to subsequent scan (p = 0.000). Previous PSA infection and neutrophilic inflammation was associated with increased prevalence of bronchiectasis at subsequent scan (OR = 2.9). Air trapping was present in 67% of initial scans, persisting in 86% of subsequent scans. Median extent increased from initial to subsequent scan (p = 0.005). Infection and inflammation did not increase risk of air trapping, but air trapping was more common in girls (OR = 2.0). Bronchiectasis and air trapping commonly occurred together. The 6 minute walk test (6MWT) and incremental shuttle walk test (ISWT) are commonly used to assess functional exercise capacity, prescribe the training intensity and measure the efficacy of pulmonary rehabilitation. No studies have compared these tests in patients with non-CF bronchiectasis.

Aims To compare peak dyspnea and heart rate (HR), and nadir oxygen saturation (SpO 2 ) during the 6MWT and ISWT in subjects with non-CF bronchiectasis.

Methods Twenty-seven participants (aged 64 ± 13year, FEV1 70 ± 17%pred, FVC 82 ± 16%pred) with non-CF bronchiectasis enrolled in a trial of pulmonary rehabilitation, completed two 6MWTs and two ISWTs in random order. Results The 6 minute walk distance (6MWD) and the incremental shuttle walk distance (ISWD) were significantly greater on the 2nd test (both p < 0.02). The mean (95% CI) increase in the 6MWD was 22 m (9 to 35 m); 4% (2 to 7%) and in the ISWD was 22 m (4 to 39 m); 6% (2 to 10%). The greatest 6MWD and ISWD was 560 ± 86 m and 446 ± 151 m respectively. There was a strong relationship between the 6MWD and ISWD (r = 0.89, p < 0.001). Peak dyspnoea was higher for the ISWT (4.2 ± 1.2 vs. 3.6 ± 1.2, p = 0.02) but there was no difference in peak HR (76 ± 11 vs. 75 ± 10% age pred maximal HR, p = 0.67) or nadir SpO 2 (93.5 vs. 93.3%, p = 0.65). Conclusion Although peak HR was similar, the externally paced, incremental nature of the ISWT may account for the higher dyspnea scores in these subjects with non-CF bronchiectasis. Future research will determine the responsiveness of the ISWT and 6MWT following pulmonary rehabilitation in this population. The six minute walk test (6MWT) is extensively used in clinical practice. However, the role of this test in people with dust-related lung disease remains unclear.

Aim The aims of the study were to investigate the relationships between exercise capacity measured by the 6MWT and the incremental peak and endurance cycle tests, the 6MWT and health-related quality of life, and the 6MWT and activity levels in people with dust-related lung disease.

Methods Thirty male participants with asbestos related pleural disease, asbestosis or silicosis performed two 6MWTs separated by 30 minutes with the better of the tests used for analysis. During the rest period, participants completed the St George's Respiratory Questionnaire (SGRQ). On a separate day, participants performed spirometry, lung volumes, DLCO and a peak and endurance cycle test. Participants wore an activity monitor (Sense-Wear Pro3) for a period of seven days. Results Mean (SD) age of participants was 71 (6) There was a significant correlation between 6MWT distance and peak watts (r = 0.67, p < 0.001) but not with endurance cycle time. There were significant correlations between the 6MWT and all components of the SGRQ, the strongest correlation being with the 'Activity' domain (r = -0.61, p < 0.001) and significant correlations between 6MWT and average daily steps (r = 0.57, p = 0.002) and average METs (r = 0.59, p < 0.001).

Conclusion Findings suggest the 6MWT may be a useful measure of exercise capacity and may reflect daily activity in people with dust-related lung disease. The 6minute walk test (6MWT) is used to assess prognosis and evaluate exercise capacity in interstitial lung disease (ILD), however the physiological load imposed by the 6MWT is unknown. This study compared cardiorespiratory responses to 6MWT and cardiopulmonary exercise testing (CPET) in ILD.

Methods Fifteen participants with ILD (nine IPF), mean age 70 (standard deviation 12) years and TLCO 57 (17) %predicted undertook CPET and 6MWT on the same day in random order. Pulmonary oxygen uptake (VO2), ventilation (VE), carbon dioxide production (VCO2), oxyhaemoglobin saturation (SpO2) and heart rate were compared between the tests using a portable metabolic cart. Relationships between 6 minute walk distance (6MWD) and peak cardiorespiratory responses on CPET were evaluated using correlations.

Results Peak VO2 measured during the 6MWT was lower than during CPET (15.1(3.5) vs 17.5 (2.6) ml.kg/min, p = 0.03). Oxygen consumption during 6MWT reached a mean of 87% of VO2peak achieved on CPET (95% confidence interval 76-98%VO2peak). Peak ventilation, carbon dioxide production and peak heart rate were significantly lower during 6MWT, but there was no difference in nadir SpO2 (90(4)% vs. 91(3)% on 6MWT and CPET respectively, p = 0.14). A higher 6MWD was associated with a higher peak work rate (r = 0.93, p < 0.001) but there were no relationships between 6MWD and peak cardiorespiratory responses on CPET.

Conclusions The 6MWT elicits a high but submaximal oxygen uptake in people with ILD. Given the poor relationship between 6MWD and peak cardiorespiratory responses elicited by CPET, the prognostic value of the 6MWT may be related to the degree of oxygen desaturation elicited by this test. Results There were no differences between groups at baseline for age, gender, body mass index or respiratory function. After twelve months both groups had similar improvement in FEF25-75%(mean 0.181 L/sec, 95% confidence interval 0.059 -0.303 L/sec). There was no significant effect on FEV1 or FVC due to either treatment allocation or time.

Both groups demonstrated significant improvements in all domains of both the SGRQ and LCQ but there was no difference between groups.

Conclusion The inhalation of both isotonic (0.9%) and hypertonic (6%) saline improved small airways function and improved quality of life over 12 months, however both treatments were equally effective. Introduction This project aimed to develop, implement and evaluate an innovative primary care model in community pharmacy for screening, monitoring and education of people with or at risk of sleep disorders (SD).

Methods A randomised control trial comparing two approaches was conducted: 1) risk assessment only (RAO) or 2) risk assessment plus overnight nasal flow monitoring using the FlowWizardÒ device (RA+). The risk assessment tool collected data on lifestyle, medical conditions, medications and included validated instruments for detecting SD. Twentythree pharmacies (12 RAO/ 11 RA+) recruited patients during a 4 month period. Patients at significant risk for a SD were provided with information and referred to a GP.

Results 295 patients were recruited (RAO n = 131, RA+ n = 164). Of these, 24.9% (RAO 19%, RA+ 29%) had an increased risk of daytime sleepiness, 27.6% (RAO 28%, RA+ 31%) were at risk of significant insomnia, 43.0% (RAO 37%, RA+ 47%) at risk of obstructive sleep apnea, and 36.9% (RAO 34%, RA+ 38%) at risk of Restless legs syndrome (RLS). Pharmacists recorded a total of 754 interventions and 94 patients were referred to their GP (1 of 3 screened). Preliminary results showed that 126 patients (RAO, n = 73, RA+, n = 53) have completed the follow-up questionnaire with 29 GP referrals being taken up and seven SD diagnosed (24% of those who took up a referral, RAO, n = 5, RA+, n = 2). Nine patients (41%) received a diagnosis other than a SD and 7 patients reported still awaiting sleep specialist assessment or testing.

Conclusion The results of this study indicate that community pharmacy is a potential site for SD screening. Support The Pharmacy Guild of Australia, Investigator Initiated Grants. Nomination Nil.

Conflict of Interest Nil.

JM FOSTER 1 , L SMITH 1 , SZ BOSNIC-ANTICEVICH 1 , T USHERWOOD 1 , SM SAWYER 2 , CS RAND 3 , HK REDDEL 1 1 University of Sydney, Australia, 2 Royal Childrens Hospital Melbourne, Australia, and 3 Johns Hopkins University, Baltimore, USA Aim To identify beliefs and behaviours associated with poor adherence which could be used to guide tailored interventions in primary care. Methods Patients aged ‡14 years with doctor-diagnosed asthma and a current ICS/LABA prescription completed questionnaires on beliefs and behaviours, side-effects, asthma control (ACQ), and underwent spirometry. Adherence with ICS/LABA was measured over 6 weeks by Smartinhalers which electronically recorded the time and date of each actuation. Univariate and multivariate analyses of 61 questionnaire items identified predictors of adherence.

Results Ninety-nine of 100 patients completed the study (57 female; mean ± SD FEV 1 % predicted 83 ± 23; ACQ 0.76 ± 0.76). Mean adherence was 75% ± 25 (n = 85). Thirty one beliefs or behaviours were significantly associated with poor adherence (p < 0.05). Factor analysis of these 31 items identified 7 themes: F1. Perceived necessity; F2. Safety concerns; F3. Acceptance of asthma chronicity and ICS/LABA effectiveness; F4. Advice from friends/family; F5. Motivation/routine; F6. Ease of use; and F7. Satisfaction with asthma management. Regression analysis demonstrated that 10 items in 5 themes independently predicted poor adherence (model adj. R sq. = 0.67; p < 0.001) including 'My preventer is necessary to keep my asthma under control'(F1), 'I get side effects from my steroid inhaler'(F2), 'I think I will have asthma for a long time'(F3), 'My family/ friends tell me I should use my preventer inhaler more often'(F4), 'I have a fixed daily routine for taking my asthma medications'(F5). Adherence was lower for patients who attributed dental deterioration or dry eyes to their ICS, but not for hoarseness. Conclusions This study identified 10 key beliefs or behaviours associated with poor adherence which may be amenable to change in patient-specific primary care interventions. Support Asthma Foundation NSW, GlaxoSmithKline (medications Investigation of pulmonary embolism with CTPA is often performed despite low clinical risk and results in unnecessary exposure to radiation and radiocontrast as well as inefficient use of medical resources. Risk stratification with a validated prediction tool (Wells score) complements clinical decision making and rationalises the use of CTPA to appropriate patient groups.

Methods Prospective assignment of Wells score by requesting clinicians on a formal algorithm form was instituted in 2009. All patients being investigated for pulmonary embolism were required to have the form filled prior to performance of CTPA. Patients stratified low clinical risk (Wells £ 2) did not proceed to CTPA unless a senior physician override was applied. Intermediate risk patients (Wells 2-6) proceeded to D-dimer measurement and if above the laboratory cutoff (0.3) proceeded to imaging. All high risk patients (Wells > 6) proceeded to CTPA directly. CTPA outcomes, D-dimer levels, request locations and dates were recorded. Data were collected from February to August 2009. Results A total of 333 patients were investigated with CTPA in this period. 65 patients (19%) did not have the Wells score assigned but 268 patients (81%) had complete data. 215 (64%) request originated from the emergency department, 107 (32%) from inpatient wards and 8 (2%) and 3 (1%) from ICU and outpatients respectively. The prevalence of pulmonary embolism in our study population was 13% similar to data from Wells and others. 57 (21%) patients were stratified to low risk, 169 (63%) to intermediate risk and 42 (16%) to high risk. The prevalences of pulmonary embolism were 9%, 12% and 24% respectively in these risk groups, comparable with published data. When evaluated against the same period in 2008, there was an absolute reduction of 136 (30%) CTPAs performed.

Conclusion Institutional implementation of a formal clinical prediction tool into the decision making process is feasible and yields significant reduction in CTPAs performed, with substantial cost savings and patient benefits. Aim To conduct an RCT to measure the impact of the Practitioner Asthma Communication and Education program (PACE) on general practitioner (GP) management of paediatric asthma.

Methods GPs recruited through local practice networks identified patients aged 2-14 with diagnosed asthma. GPs received two 3 hour interactive workshops.

Results Outcome data were collected from 57 intervention and 49 control GPs, and 106 intervention and 107 control families. A significantly higher percent of intervention GPs than control GPs reported frequently providing a written asthma action plan (23.2%, P = 0.03, NNT = 4.3).Intervention GPs reported higher rates of giving written instructions to adjust medication (18.4%, P = 0.01, NNT = 5.4) and of providing spacers (28.7%, P = 0.01, NNT = 3.5). A significantly higher percent of intervention group children had received a written asthma action plan in the last year (15.2%, P = 0.03, NNT = 6.6).

Fewer intervention group children with infrequent intermittent symptoms were using regular ICS (24.0%, P = 0.03, NNT = 4.2). Intervention GPs had higher improvements in confidence (21.5%, P = 0.03), helpfulness (20.7%, P = 0.04) and frequency of using the taught communication strategies (21.1%, P = 0.03).

Conclusion The PACE program is the most robustly evaluated program of GP asthma education in Australia. Our results provide high level evidence that paediatric asthma management is improved by PACE. PACE may be useful for educating other health professionals involved in chronic disease management. Support Australian Government Department of Health and Ageing. Nomination Nil.

Conflict of Interest Nil.

VINCENT SIAW, KARMEN YAI, ANAND ROSE Department of Respiratory Medicine, Flinders Medical Centre, Bedford Park, South Australia, Australia

Pulmonary Embolism is a common cause for presentation to the emergency departments of tertiary hospitals. If undiagnosed it has a 30% mortality. The diagnostic algorithm includes a clinical assessment, D'dimer assays and imaging in the appropriate patient. The preferred tool in our institution for confirming a diagnosis of a pulmonary embolism is the CT Pulmonary Angiogram (CTPA). We decided to audit our practise of doing a clinical assessment using a standardised risk score (eg.Wells score) prior to requesting a CTPA. Aim To audit the use of standardised clinical risk assessments prior to requesting a CTPA when a pulmonary embolism is suspected.

Methods CTPA requests from the emergency department from February and March 2009 were retrieved. Cases notes were screened for mention of the Wells or Geneva scores. Individual symptoms were also studied in attempt to reconstruct the score from the notes.

Results Of the 189 CT Pulmonary angiograms performed -52 requests were from the Emergency Department. Of these requests 15.4% (8 patients) were positive studies. Systematic clinical risk assessment had been used in 23.1% (12 cases). When a systematic clinical score was performed 33.3% of the CTPA studies were positive. This was greater than when no risk score was performed (10% of CTPA studies returned positive). We aimed to compare GP and parent reports of asthma management styles from an RCT of Practitioner Asthma Communication and Education (PACE). Methods GPs recruited through local networks identified patients aged 2-14 with diagnosed asthma. Intervention GPs participated in two 3 hour workshops of patient education and communication techniques. Results At 12 months, 106 GPs (57 intervention, 49 control) and 213 parents (106 intervention, 107 control) provided data. More intervention GPs (50.0%) reported checking device use (vs. 39.1%; diff = 10.9%, p = 0.33). Intervention parents (53.6%) reported that GPs checked their device use more frequently (vs. 47.5%; diff = 6.1%, p = 0.47). More intervention GPs (83.9%) reported providing educational messages (vs. 72.3%; diff = 11.6%, p = 0.24). However, more control parents (40.4%) (vs. 35.7%; diff = -4.7%, p = 0.59) reported receiving messages. More control GPs (56.5%) said they asked patients about new medication fears (vs. 52.6%; diff = -3.9%, p = 0.85), but more intervention parents (8.5%) reported being asked about this (vs. 5.6%; diff = 2.9%, p = 0.58).

Conclusions GP and parental reports of device use checking were consistent. Reports of educational messages and communication were less consistent, though these may have been provided or used but not recognised by parents. These findings highlight that parents and their GPs can have very different perceptions of some aspects of a child's asthma management. Care should be taken when selecting outcome measures for clinical trials. Support Australian Government Department of Health and Ageing. Nomination Nil.

Conflict of Interest Nil.

TO 080

Background Smoking cessation interventions in outpatient settings has been clearly demonstrated to be one of the most cost effective strategies available in reducing disease burden. Given the evidence of superior benefits with over nicotine replacement therapy, we aimed to evaluate its benefit in the inpatient setting for smokers admitted with acute smoking related events.

Methods Adult patients (n = 151, 20-75 years) recruited from the Respiratory, Cardiology, Neurology, Vascular and general medical wards of The Queen Elizabeth Hospital, Lyell McEwin Health Service and the Royal Adelaide Hospital were randomised to receive either VT (varenicline tartrate) plus Quit SA counselling (n = 77) or Quit SA counselling alone, (n = 74).

Results Preliminary analysis shows that after three months of follow-up, smoking abstinence was achieved by 28.4% in the control and 44.2% in the intervention group, (p = 0.062). Preliminary subgroup analysis indicates that cardiac patients, (n = 71) have gained the most benefit with 49.3% obtaining continuous abstinence.

Conclusion Whilst a beneficial smoking cessation trend is evident at three months, these are only preliminary results. Our recruitment target sample size is likely to provide sufficient power to identify significant differences in abstinence rates between treatment and control groups, and permit sub-group analyses of treatment effect based upon inpatient characteristics. Support Nil. Nomination Nil. Introduction Cigarette smoking prevalence has been in decline in Australia over many decades but prevalence remains high in lower socioeconomic groups. Hospital employees span the socioeconomic spectrum but there are few data on smoking prevalence from these sites. The visibility of smoking on campus conflicts with the health message that hospitals should promote but cessation services are often not provided. The Queen Elizabeth Hospital (TQEH) has had an ongoing Stop Smoking Service (using cost-price NRT and counselling) provided by TEJ since 1995 and 5-yearly surveys are conducted to assess benefits and ongoing need. Methods Employees of three metropolitan teaching hospitals (Royal Adelaide -RAH, Flinders Medical Centre -FMC and TQEH) and the Alice Springs Hospital (ASH) were sent a single page questionnaire asking about smoking status and views about smoking on campus. Returns were voluntary but encouraged via a small monetary prize. TQEH was surveyed thrice (1997, 2002 and 2007) , the other hospitals were surveyed once (late 2004/ early 2005) .

Results Almost all employees reported knowing smoking is a health hazard. Most employees (smokers & non-smokers) at all hospitals, thought smoking in public view was unacceptable but support for a total ban was less than for suitable areas where smoking was allowed. TQEH smoking prevalence is much lower than the comparator hospitals where prevalence is similar to national prevalence ( Introduction Interleukin-17A is a cytokine released from T helper 17 (Th17) cells which induces and mediates various pro-inflammatory responses. As a result, IL-17A has been linked to many immune/autoimmune related diseases but its role in COPD has not been explored. In the present study we investigated whether IL-17A regulates cigarette smoke (CS)-induced lung inflammation.

Methods Wild-type (WT) or mice deficient in IL-17A (IL-17A -/-) were placed in a perspex chamber and exposed to CS generated from nine cigs per day for 4 days. In separate experiments, CS-exposed WT mice were treated with anti-IL-17A antibody. On the fifth day, mice were killed, the lungs lavaged with PBS and then harvested for genomic analysis.

Results WT mice exposed to CS for 4 days had significantly more BALF macrophages (4.3 ± 0.3(SEM) · 10 5 ) and neutrophils (3.8 ± 0.3 · 10 4 ) than sham-exposed mice (1.0 ± 0.2 · 10 5 and 0, respectively) (n = 5-26, p < 0.05). However, CS-exposed IL-17A -/mice had significantly fewer macrophages (2.1 ± 0.1 · 10 5 ) and neutrophils (0.6 ± 0.1 · 10 3 ) than CS-exposed WT mice (n = 5-26, p < 0.05). Macrophage and neutrophil numbers in sham-exposed IL-17A -/mice (1.2 ± 0.1 · 10 5 and 0.3 ± 0.2 · 10 3 ) were similar to those of sham-exposed WT mice. Gene expression analysis by QPCR showed that CS-exposed IL-17A -/mice had markedly reduced MCP-1, TNFa, IL-17A, IL-23 and MMP-12 expression compared to CS-exposed WT mice. Treatment of CS-exposed mice with anti-IL-17A antibody significantly reduced CS-exposed BALF macrophages and neutrophils (n = 8, p < 0.05). In addition, we found that lungs of NOD-SCID mice deficient in T & B lymphocytes expressed IL-17A in response to CS.

Conclusions These data show that IL-17A regulates CS-induced lung inflammation and that targeting IL-17A may have therapeutic utility in inflammatory lung diseases where CS plays a role. Introduction In utero exposure to tobacco constituents may contribute to respiratory health problems later in childhood. Glutathione S-transferases (GSTs) are important in detoxification of xenobiotics. A reduction in the mother and fetus's detoxification ability due to genetic variation in GSTs could expose the fetus to higher levels of toxins.

Objective To investigate the interactive effects of maternal smoking during pregnancy with maternal and infant GST genotypes on airway responsiveness (AR) and lung function in infancy at 1, 6 and 12 months and longitudinally throughout the first year. Methods GSTT1, GSTP1 and GSTM1 were genotyped in infants and mothers using PCR. In utero exposure to maternal smoke was evaluated by questionnaire, AR was assessed by histamine challenge and V'maxFRC was measured using the rapid thoracoabdominal compression technique.

Results GSTT1 non-null in infants, mothers or both was associated with reduced AR at 12 months and throughout the first year and increased V'maxFRC at 6 months. Maternal GSTP1 Val/Val or Ile/Val was associated with increased V'maxFRC at 6 months. In infants exposed to in utero smoke, GSTT1 non-null infants, mothers or both was associated with reduced AR at 1 month and throughout the first year and increased V'maxFRC throughout the first year. There were no significant associations with GSTM1.

Conclusion GST genes may be especially important during fetal development as they may modify, through proficient detoxification, the effects of in utero maternal smoke exposure on AR and lung function in infants.

Funding NHMRC.

Conflict of Interest No.

Introduction There are few birth cohort studies in which frequent, contemporary measures of tobacco smoke exposure have been related to lung function and airway responsiveness in later childhood. Aim To examine the effects of in utero and post natal exposure to ETS on lung function and airway responsiveness at age 8 years.

Methods Children with a family history of asthma were recruited antenatally into a randomized trial of house dust mite avoidance and dietary modification 1 Results A total of 220 subjects were enrolled (105 Indigenous Australians, 115 Indonesians). In the Indigenous Australian setting the SGRQ total score was independently associated with exacerbation frequency and lung function (% predicted FEV1) whilst the symptom score was associated more strongly with AE frequency and activity score with lung function. In Indonesians with PTB the total SGRQ score correlated with treatment response over time as well as lung function (% predicted FVC), exercise tolerance (6MWT) and the extent of involvement on CXR.

Conclusions In an Indigenous Australian and Indonesia, setting respiratory-related QoL using a modified SGRQ correlates with lung function, exercise performance, disease activity and treatment. These tools should be a useful addition to evaluating interventions in this setting. Background Epithelial mesenchymal transition is a process in which airway epithelial cells disaggregate and then migrate through the reticular basement membrane (Rbm) into the lamina propria to become myofibroblasts. The aim of this study was to identify if EMT is active in the airways in smokers, and whether relevant to COPD. Methods Endobronchial biopsies (ebb) from current smokers with COPD (CS; n = 17) and ex-smokers with COPD (ES; n = 15), smokers with normal lung function (NS; n = 16) and never-smoking controls (NC; n = 15) were stained for EMT markers, S100A4 a fibroblast protein, epidermal growth factor receptor (EGFR) and matrix metalloproteinase-9 (MMP-9). Computer-assisted image analysis was used to quantify the expression of markers in biopsies and slides were counted by an observer blinded to subject and diagnosis. We used non-parametric statistics.

Results Compared to NC, there was significant fragmentation of the Rbm in CS, ES and NS groups (p < 0.001), which was especially marked in CS and was positively related to pack years in COPD subjects (R = 0.41, p = 0.02). CS, NS and ES demonstrated increased staining for: basal epithelial S100A4 (p < 0.004), epithelial EGFR (p < 0.001) and MMP-9 (p < 0.002) for cells in Rbm 'clefts', and Rbm cell S100A4 (p < 0.001) compared to NC. There was increased Rbm cell S100A4 staining in CS vs. ES and NS (p < 0.007). Basal epithelial cells staining for S100A4 correlated negatively with airflow limitation (R = -0.49, p = 0.04) in CS, and dual staining revealed that basal S100A4 positive cells co-stained with vimentin (an additional mesenchymal marker).

Conclusions Our findings suggest that EMT is active in smokers, and is most evident in current smokers with COPD, suggesting a role in COPD pathogenesis. Pulmonary emphysema is a major component of the Chronic Obstructive Pulmonary Disease (COPD), and also predisposes affected individuals to lung cancer. Emphysema can be a familial or acquired disease, with the great variation in development of disease in atrisk populations reflecting the influence of other susceptibility determinants. In this regard, the IL-6 cytokine family has been linked with emphysema pathogenesis. However, studies into the definitive mechanisms by which these cytokines cause emphysema have been hampered by the absence of informative animal disease models. To address this issue, we have utilized a sophisticated animal model (gp130 F/F mice) with a subtle mutation in the IL-6 cytokine family receptor gp130 which, as a consequence of abolishing binding of both SHP2 and SOCS3, simultaneously mediates STAT1/3 hyper-activation and impaired SHP2-MAPK and -PI3K activation. The gp130 F/F mice spontaneously develop emphysema by 6 months of age characterized by increased static compliance. Lung Stereology has further confirmed emphysematous changes, revealing increases in volumes of airspace and lung. Among the IL-6 cytokine family, IL-6 expression is significantly up-regulated in the lungs of gp130 F/F mice, and genetic ablation of IL-6 in gp130 F/F mice prevents the development of emphysema. Notably, an increased apoptosis of alveolar cells has been identified as the underlying cellular mechanism associated with the emphysema in gp130 F/F mice. Collectively, our observations identify for the first time that deregulated gp130 signalling by IL-6 cause's alveolar cells to undergo apoptosis, which coincide with the pathogenesis of emphysema. Furthermore, this mouse model has the enormous potential to allow us to explore common mechanistic links between COPD and lung cancer.

Supported by The NHMRC, Australia.

Conflict of Interest No.

Introduction Despite smoking cessation, susceptible COPD patients continue to decline in lung function. Understanding biological pathways and their gene ontologies would help to develop better treatments and diagnostic methods for COPD. The aims of this study were to identify gene ontologies associated with mild and moderate COPD by (i) profiling mRNA and (ii) miRNAs and their predicted targets.

Methods Profiling was performed on total RNA extracted from lung tissue of 30 COPD patients undergoing resection for lung cancer. Microarray platforms (Operon V2 and Agilent G4470 V1) were used to characterise mRNAs and miRNAs respectively. Analysis was performed using BRB Array Tools V8.3 and GSEA.

Results The 30 patients were Caucasian former smokers with mean (SD) age 68 (6), FEV1 72 (17) % predicted, KCO 70 (10)% predicted and pack years 71 (44). We identified authentic candidate genes (p < 0.01) that predicted COPD progression with 70% accuracy in in-house and public datasets. Genes involved in cell cycle, proliferation, development and growth were identified. Increasing expression of miR-34c, a candidate miRNA for emphysema progression, on lung fibroblast and epithelial cells downregulated predicted mRNA targets with potential biological role in COPD.

Conclusions We have identified multiple gene ontologies associated with COPD severity. These targets have promising biological roles in COPD and can be further developed as biomarkers or therapeutic targets. Cigarette smoke (CS)-induced oxidative stress is known to drive the pathogenesis of COPD. The antioxidant glutathione (GSH) is essential for efficient macrophage functions including phagocytosis of apoptotic cells (efferocytosis) which we have shown to be defective in COPD. GSH synthesis is controlled by a CD98/xCT cysteine transporter pathway. CD98 is also a ligand for galectin-3 (gal-3), a lectin important for macrophage phagocytosis and GSH synthesis. We hypothesised that targeting oxidative stress in COPD by increasing GSH would increase gal-3 levels and improve efferocytosis. We investigated (a) Ex vivo: oxidative stress markers (8-isoprostane; MMP9), GSH and gal-3 in BAL from 20 controls and 14 current-and 13 ex-smoker COPD subjects (b) In vitro: the effects of CS on alveolar macrophage production of gal-3 and GSH (c) In vivo: the effects of treatment with a GSH precursor, Procysteine, on efferocytosis, gal-3 and GSH in smokeexposed mice. Procysteine was administered in semi-solid mouse feed. Efferocytosis was investigated in lung tissue and BAL macrophages. 8-isoprostane and MMP9 were significantly increased in BAL in current-and ex-smokers with COPD. GSH and gal-3 were decreased in COPD (Gal-3, ng/mL: current 0.66 ± 0.11, ex-smoker 0.96 ± 0.26 vs. controls 3.0 ± 0.62). In vitro CS treatment decreased gal-3 expression. In vivo, CS caused decreased efferocytosis that was significantly improved by Procysteine (Control; smokeexposed; Procysteine + smoke-exposed: BAL 26.2%; 17.66%; 27.8%; Tissue 35.9%; 21.6%; 34.5 %). GSH and gal-3 were also significantly increased by Procysteine (Gal-3, ng/ml: control 1.74 ± 0.21; smoke-exposed 0.26 ± 0.042; Procysteine + smoke-exposed 1.26 ± 0.29 ng/ml). Targeting oxidative stress is a viable approach to improve macrophage dysfunction in COPD. Support NHMRC, ARC.

Introduction Our knowledge about the effects of inhaled corticosteroids (ICS) on airway remodelling in chronic obstructive pulmonary disease (COPD) is limited. We have previously reported that in bronchial biopsies (BB) from COPD subjects the reticular basement membrane (Rbm) is fragmented and hypervascular. In this study we have examined the effects of ICS on these airway remodelling changes in COPD.

Methods In a double blind and randomised study we compared the effects of 6 months of fluticasone propionate (FP, 0.5 mg/twice daily) with placebo. BB were stained with collagen IV antibody to mark vessel endothelial basement membrane. The length of Rbm splits and the number and area of vessels in the Rbm were compared before and after treatment.

Results COPD subjects were randomized 2 : 1 to receive either FP (n = 15) or placebo (n = 7). There were no differences between the groups before treatment. Introduction COPD is a complex disease characterised by fixed airflow obstruction and neutrophilic airway inflammation. Markers of systemic inflammation such as serum amyloid A (SAA) are elevated in COPD. However, little is known about the relationship between airway and systemic inflammation. This study tested the hypothesis that systemic inflammation is associated with airway neutrophils in COPD.

Methods Participants with COPD (n = 65, >55 years, with FEV1/FVC <70 and FEV1% predicted <80) and healthy controls (HC; with normal lung function n = 32 > 55 years) underwent clinical assessment, spirometry, blood collection for SAA, IL-6 and CRP and sputum induction. Sputum was processed for differential cell count and mediators.

Results Airway proportions of neutrophils and eosinophils, levels of IL-8, total MMP-9 and gene expression of IL-6 were increased in participants with COPD. Serum IL-6 (median q1-q3; (2.9 (1.7-4.9)) vs. Asbestos-related lung cancers (ARLC) account for 4-12% of all lung cancer, and are difficult to distinguish from non-asbestos related tumours (NARLC) by clinical and histological criteria. We hypothesised that whole genome array comparative genomic hybridization (aCGH) profiling could identify regions of gain and loss common and specific to asbestos-related lung cancer. Methods The aCGH profiling by Agilent CGH 44B arrays was performed on 64 primary non-small cell lung cancers obtained from The Prince Charles Hospital (TPCH) lung tumour bank. Lung cancers occurring in individuals with >=20 asbestos bodies/gram wet weight (AB/gww) of lung tissue were defined ARLC and individuals with 0 AB/gww were defined NARLC. Genome breakpoints were called using the Circular Binary Segmentation algorithm implemented in DNACopy. Recurrent regions of amplification and deletion were identified using the Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm developed by the Broad Institute, controlling for false discovery rates (q < 0.05).

Results GISTIC identified recurrent copy number gains in 3q28 and NARLC at q < 0.05 but none for ARLC at the same threshold. TO 093

Introduction The relationship between asbestos exposure and asbestos related diseases (ARD) such as asbestosis, lung cancer and mesothelioma are well established. Less is known about asbestos exposure and non-ARD respiratory diseases. Aim To investigate respiratory symptoms and lung function in former workers and residents from Wittenoom who have not developed an ARD. Methods An annual review, which includes lung function, plain chest x-ray and respiratory questionnaire, is conducted on a cohort of ex-workers and ex-residents from Wittenoom. Only those who had been reviewed within the previous 5 years and had not developed an ARD, nor had plain chest radiographic evidence of asbestosis, were included in the analyses. The prevalence of respiratory symptoms was determined and standardised lung function z-scores calculated. Predictors of symptoms and lung function were assessed using both multiple logistic and linear regression.

Results Questionnaire data was available for 690 subjects (264 women, 264 ex-workers; mean age 61.7 ± 10.7 years), while acceptable lung function data was available for 631 subjects (249 women, 258 ex-workers). The prevalence of reported symptoms ranged between 20 and 30% for wheeze, cough, sputum, shortness of breath and bronchitis. Pack years of smoking and/or being an ex-worker were the main risk factors for symptoms. Standardised lung function scores (95%CI) for the total group were -0.66 (-0.75--0.57), -0.80 (-0.89--0.71) and 0.36 (0.27-0.44) for FEV, FVC and FEV/FVC respectively. Both pack-years and cumulative asbestos exposure were independently associated with reduced FEV and FVC.

Conclusions People previously exposed to asbestos, particularly ex-workers, have high rates of respiratory symptoms which are mostly related to smoking. Reduced lung function in the cohort was associated with both smoking and cumulative asbestos exposure.

Conflict of Interest None.

Introduction Malignant Mesothelioma (MM) is an aggressive cancer with a very poor prognosis. Interactions of the components of the extracellular matrix (ECM) are now known to be important for the growth and regulation of cancer cells. TGFb is an important regulator of the ECM and in particular collagen. Previous data in our laboratory has shown that blocking TGFb signaling by using TGFb antibodies inhibits collagen production and MM growth.

Aim to determine the signaling pathways downstream of TGFb that are important in the regulation of collagen expression in MM.

Methods Components of the TGFb pathway were inhibited by use of chemical inhibitors and overexpression of the endogenous inhibitor Smad7 in control and MM cell lines. Collagen levels were measured by realtime PCR.

Results Collagen regulation is thought to occur through the classic Smad2/3 signaling pathway. Our data show that Smad7 overexpression inhibits TGFb-induced collagen production in normal mesothelial cells and the mesothelial cell line MET-5A but not in the MM cell lines investigated. Therefore, the Smad2/3 pathway for collagen regulation appears to be altered in malignant mesothelioma. It was shown that Smad2/3 are expressed, phosphorylated and activated by TGFb in the MM cell lines. Our results indicate that nuclear import of Smad4, which is responsible for the nuclear import of Smad2/ 3, is altered in MM. Aim To characterise impedance variability at 6 Hz in asthma and its relationship to asthma severity. Methods A school-based cohort of 38 non-asthmatic children, aged (mean (SD)) 9.5 (1.8) years (UPTECH feasibility study) were tested on two occasions 2 weeks apart. An asthma camp cohort of 22 asthmatics, aged 10.5 (1.

2) years, were tested daily for 5 days. Mean Resistance (Rrs 6 ) and reactance (Xrs 6 ) of at least three technically acceptable one minute recordings were reported. Medications were not withheld. Variability was assessed by Intraclass Correlation Coefficient (ICC) and within-subject Standard Deviation (SD W ) using first and last testing day data, and all 5 days of data for SD W severity comparison amongst asthmatics.

Results Repeat FOT measures at 6 Hz were obtained in 34/38 non-asthmatic children. Mean (SD) Rrs 6 and Xrs 6 was 6.89 (1.1) and -1.57 (0.52) for the UPTECH cohort, and 5.68 (1.12) and -1.27 (0.55) cmH 2 O/l/s in the asthma camp cohort respectively. Rrs 6 variability was increased in asthmatics. Rrs 6 variability tended to be higher in persistent vs. intermittent asthmatics but did not reach statistical significance (p = 0.07).

Non asthmatic (n = 34) Introduction Our Cochrane review examining the efficacy of using FeNO to tailor the dose of inhaled corticosteroid showed that FeNO cannot be routinely recommended for clinical practice at this stage and remains uncertain. However all the 6 studies used a single FeNO cut-off. In this RCT we determined if asthma monitoring using FeNO (using two different cut-offs dependent on atopy) is better than control (symptoms and FEV 1 ) in preventing asthma exacerbations in children on inhaled corticosteroids. Methods Over 12-months, children underwent spirometry, FeNO, QOL and asthma/ cough diary during every visit. Treatment for asthma was adjusted according to pre-determined criteria taking into account atopy status and dependent on allocation group (FeNO or control).

Results About 63 children were randomised-FeNO group (N = 31, median age 10.2, IQR 5.75), or control group (N = 32, median age 10.1, IQR 5.69). Significantly fewer children in the FeNO group had asthma exacerbations compared to the control group (6 vs. 15; p = 0.021) over 12-months. Number needed to treat (NNT) to prevent one child from having any exacerbation in 12 months = 4 (95%CI 3, 24). Parental QOL improved in FeNO group at final visit in comparison to the QOL in control group (p = 0.042). FEV 1 increased in both groups over the duration of the study but there was no difference between the groups when measured at baseline (p = 0.661) and at final (p = 0.385).

Conclusion Tailoring of asthma medications in accordance to FeNO levels (compared to usual management), taking into account atopy status, reduces asthma exacerbations and improves asthma QOL. However both strategies equally improved FEV 1 . Background Inhaled corticosteroids have a modest effect on improving symptom control in preschool asthmatic children. Delivery of inhaled steroids with pMDI-spacers are influenced by children's proficiency in spacer technique, and adherence to prescribed medication.

Aim To investigate the influence of an incentive spacer (Funhaler), on spacer technique, adherence to treatment, and asthma control in preschool asthmatic children.

Methods About 132 children aged 2-6 years, and being prescribed regular inhaled steroids in the community were randomised to receive regular inhaled fluticasone through either an Aerochamber Plus Ò , of a Funhaler Ò . Subjects were followed up three monthly for a year. Proficiency in spacer technique was measured at each visit by measuring the amount of salbutamol inhaled from spacer onto a filter interposed between subject and spacer. Adherence was monitored by Smartinhaler Ò electronic devices. Symptoms were recorded on diary cards for a week before each study visit.

Results There was no difference between the Funhaler group and the Aerochamber group in terms of adherence to medication or measures of asthma control (p > 0.05). Spacer technique was significantly better in the Funhaler group in subjects younger than 4 years of age at time of randomisation (p < 0.00). There was large inter subject variation in drug dose inhaled on filter, ranging from 0 -100% (drug dose recovered from filter, as percentage of total dose recovered), and mean adherence over each 3 month period ranging from 0-100%. Discussion The Funhaler Ò does not improve clinical outcome, but improves spacer technique in children younger than 4 years of age. The large variability in adherence and drug delivery should encourage both efforts to improve adherence, and efforts to standardise inhaled drug delivery in preschool children. 1990-1994 and 2005-2007 . About 75% of OB cases were notified within 1 year of arrival. 30 of the Australianborn cases were close household contacts of an adult TB case. About 18 cases had culture confirmed disease (15 fully sensitive to first line drugs, one multidrug resistant). 70% had pulmonary and 23% had lymph node TB. About 82 cases completed the treatment, two were lost to follow-up and one died. Compared to adult TB cases, children were more likely to be refugees (OR 2.1 (CI 1.1-3.7)), diagnosed on contact screening (OR 14.4 (7.9-25.8)), have lymphatic TB (OR 2.54 (CI 1.5-4.3)), and less likely to be culture-confirmed (OR .07 (CI .04-.12)). The PNG child visitors' cases diagnosed in Queensland had a higher level of severe and culture-confirmed disease. Conclusion Queensland has a very low burden of childhood TB, indicating low levels of TB transmission in the community. HRGM children, especially refugees, will remain at risk due to infection acquired overseas. Contact screening is an important method of diagnosing early TB, and refugee screening and preventive treatment may play a role in protecting this group. Funding Support Nil.

Conflicts of Interest Nil.

Introduction In response to injury, normal and efficient epithelial repair is essential in order to maintain barrier integrity and immune function. However, aberrant repair has been suggested as a contributor to disease progression in asthma. Many studies have only included subjects with atopic asthma and thus any intrinsic epithelial abnormality common to all asthmatic phenotypes is difficult to isolate. This study aimed to assess whether epithelial repair is dysregulated in asthmatic subjects and if this is common to the disease or is phenotype specific. The regulatory mechanisms promoting the cellular proliferation and migratory aspects of the repair process were also assessed.

Methods Paediatric airway epithelial cells (pAEC) of atopic and non-atopic healthy and asthmatic subjects were isolated by non-bronchoscopic bronchial brushings. Culture monolayers were wounded using an in-house wounding device, and the percentage of wound closure determined daily. Proliferation and migration were also assessed over the course of repair using Western Blot.

Results pAECs from healthy non-atopic (pAEC HNA ) and healthy atopic (pAEC HA ) subjects successfully achieved full wound closure between 8-10 days. In contrast, atopic asthmatic (pAEC AA ) and non atopic asthmatic (pAEC NAA ) subjects failed to fully repair and only achieved 40% wound closure by 10 days. Protein analysis showed a 4-fold increase in proliferation and 2-fold increase in migratory markers during repair in pAEC HNA . However, reduced proliferation and no migration activity were seen in pAEC AA. Conclusion Atopic and non-atopic asthmatic epithelial cells possess dysfunctional repair profiles in response to mechanical wounding. Results suggest dysregulated repair is an intrinsic epithelial abnormality in asthma and this appears to be independent of phenotypic criteria or atopy. Introduction Refractory chronic cough is associated with increased cough sensitivity. Speech pathology intervention has been shown to be an effective intervention for refractory cough but the mechanism behind the improvement is not known. This study provides objective measures of the mechanism and the number of treatments required to effect a response.

Methods Adults with chronic cough (n = 17) were assessed before, during and after speech pathology intervention. The primary outcome measures were capsaicin cough reflex sensitivity, automated cough frequency detection and cough-related quality of life.

Results Participants responded to the treatment with a significant improvement in coughrelated quality of life, p = 0.002, cough reflex sensitivity, C5: Mean ± SD 13.2 ± 15.8 vs. C5:174.9 ± 227.3 lMol/L, p = 0.013, cough frequency CF: 72.5 ± 55.8 vs. 25 ± 27.9 coughs/hr, p = 0.009, cough threshold CT: 4.21 ± 3.83 vs. 46.9 ± 69.1 lMol/L, p = 0.009, and urge-to-cough UTC: Median (IQR), 5(1) vs. 1(4), p = 0.01. Conclusion Speech pathology management is an effective treatment for refractory chronic cough. The mechanism behind the improvement is due to reduced laryngeal irritation which results in decreased cough sensitivity, improvement in cough symptoms, laryngeal symptoms, and cough quality of life. Introduction Airway hyperresponsiveness (AHR) is a characteristic feature of asthma. In young asthmatics, severity of AHR is related to exhaled nitric oxide (eNO), a marker of eosinophilic airway inflammation, and ventilation heterogeneity in the conducting airways (Scond). With increasing age, eosinophilic inflammation decreases and ventilation heterogeneity in the very peripheral, acinar, airways worsens. Aim To determine if the predictors of AHR differ in young and older asthmatics. Methods About 61 young (18-46) and 41 older (50-80) asthmatic subjects underwent baseline spirometry, body plethysmography, eNO, multiple breath nitrogen washout (MBNW), and methacholine (MCh) challenge. AHR was expressed as dose response slope (DRS = %fall FEV1/lmol MCh). Ventilation heterogeneity of the conducting (Scond) and acinar (Sacin) airways were calculated from the MBNW. Predictors of AHR in each group were determined by multiple linear regression. Results Compared to younger asthmatics, older asthmatics had lower values of eNO, less severe AHR, worse acinar heterogeneity; however there were no differences in Scond values. In younger asthmatics, AHR was predicted by FEV1/FVC (partial r 2 = 0.29), eNO (partial r 2 = 0.13) and Scond (partial r 2 = 0.06) (overall r 2 = 0.48, p < 0.0001). In older asthmatics, AHR was predicted by RV % predicted (partial r 2 = 0.29), Sacin (partial r 2 = 0.17) and FEV1 % predicted (partial r 2 = 0.05) (overall r 2 = 0.51, p < 0.0001). Conclusions The predictors of AHR are different in young and old asthmatics. In older asthmatics, eNO is not a significant predictor of AHR, which may reflect the changing inflammatory profile associated with aging. The association between AHR and both RV and Sacin suggests that AHR in older asthmatics is determined by abnormalities in very peripheral airways. Introduction In this systematic review and meta-analysis, we sought to establish if maternal asthma is associated with an increased risk of adverse perinatal outcomes associated with size at birth and timing of birth. Methods Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between 1975 and March 2009 were considered for inclusion. 103 articles were identified, and 40 publications involving 1,637,180 subjects met the inclusion criteria, by reporting at least one perinatal outcome in pregnant women with and without asthma. Meta-analysis was conducted with subgroup analyses by study design and active asthma management. Results Maternal asthma was associated with an increased risk of low birth weight (relative risk [RR] 1.46, 95% confidence interval [CI] 1.22, 1.75), small for gestational age (SGA, RR 1.22, CI 1.14, 1.31), very SGA (RR 1.27, CI 1.18, 1.37), significantly reduced mean birth weight (weighted mean difference -93 g, CI -169, -25 g), and reduced risk of high birth weight (RR 0.84, CI 0.74, 0.95). Maternal asthma was associated with an increased risk of preterm labor (RR 1.71, CI 1.14, 2.57), early preterm labor (RR 1.93, CI 1.58, 2.34) and preterm delivery (RR 1.41, CI 1.22, 1.61). The risk for preterm labor and delivery was reduced to a non-significant level in those studies reporting active management of asthma during pregnancy (RR 0.95, CI 0.73, 1.26; RR 1.07, CI 0.991, 1.26). Conclusion Pregnant women with asthma are at increased risk of perinatal complications which affect the baby's size and timing at birth. Active asthma management may reduce the risk of preterm labor and delivery.

With threats of new pandemic strains of influenza A virus and resistance to anti-virals there is a need for novel therapeutics that reduce viral replication and lung pathology. The pathology arising from pandemic influenza is due to an excessive host response characterised by a rapid, massive infiltration of inflammatory cells of the innate immune system into the airways leading to excessive reactive oxygen species (ROS) production. Thus, we investigated the primary enzymatic source of inflammatory cell ROS, Nox2-containing NADPH oxidase, as a novel target against lung inflammation and pathology caused by influenza A viruses of varying virulence. WT and Nox2 -/--mice were

10 4 PFU/mouse) or high virulence

Following infection with X-31, lungs of Nox2 -/-mice displayed a significant reduction in viral titre (~40-50%), macrophages, peribronchial inflammation and MCP-1 compared to virusinfected WT mice. Lung levels of IL-1b were approximately 3-fold higher in Nox2 -/-mice. BALF macrophages, neutrophils, and T lymphocytes of Nox2 -/-mice produced minimal superoxide compared to controls. The magnitude of BALF and spleen influenza-specific DbNP366+ and DbPA224+ CD8 + T cells were similar in WT and Nox2 -/-mice indicating that the major mechanisms of the adaptive immune response that effectively clear influenza A virus are preserved in Nox2 -/-mice. In vivo administration of the Nox2 inhibitor apocynin (5 mg/kg/day) significantly suppressed viral titre, airways inflammation and inflammatory cell superoxide following infection with X-31 or PR/8 strains. In conclusion, Nox2 inhibition should be considered for seasonal and pandemic control of the mortality/ morbidity induced by influenza A virus, irrespective of the strain

Department of Respiratory Medicine

Australia, 3 Cooperative Research Centre for Asthma and Airways, New South Wales, Australia, and 4 Department of Respiratory Medicine

Therefore the aim, of this study was to examine the impact of a standard, 8-week exercise-based PR program on PAL. Methods About 19 subjects (65 (9) years) with COPD (FEV1% predicted = 58 (22)) completed PR where they undertook twice weekly exercise classes consisting of one hour of upper and lower limb strengthening exercise and aerobic exercise. PAL was estimated using a multi-sensor device (SenseWear, Healthware Bodymedia) worn for a 7 day period. An index of PAL was derived by dividing total daily energy expenditure in metabolic equivalents (METS) by whole night sleeping energy expenditure (average of 3 nights sleeping). PAL was measured in the week immediately prior and in the immediately following PR. Results Despite a significant increase in six minute walk distance (6MWD), PR resulted in no change in PAL

COPD patients failed to increase their PAL. While changes in PAL may take longer to elicit i.e. the change in PAL may be delayed following PR, it is possible that the current focus of PR on increasing outcomes such as 6MWD may be too narrow to elicit changes in PAL

Little is known regarding the use of ACTs in patients admitted with AECOPD in Australia. This survey aimed to identify current practice and opinion of Australian hospital physiotherapists concerning ACTs. Methods Paper-based surveys were distributed to physiotherapists of 112 'large' and 'principal referral' Australian public hospitals (identified via a Government health report). A response rate of 81% (n = 95 hospitals) yielded 189 surveys for analysis. Results Most physiotherapists (65%) prescribe ACTs for 60-100% of patients with AE-COPD, with 90% of ACT treatments lasting 5-20 minutes. The techniques most frequently used for airway clearance were physical exercise (57%) and the active cycle of breathing technique (41%). The main influences on choice of ACT were precautions or contraindications to individual techniques (78%) and the degree of patient dyspnoea (72%). Many physiotherapists (68%) prescribe ACTs with the aim of enhancing a patient's recovery from AECOPD and 73% perceive airway clearance to be fairly or very important to the overall management of AECOPD. There was mixed awareness of the evidence for ACTs in AECOPD, with 43% of physiotherapists citing it as supportive

Conclusion Australian physiotherapists frequently use ACTs for patients with AECOPD and perceive their role to be important. Physical exercise is the present modality of choice to achieve airway clearance

Acknowledgements NH&MRC, Cure4CF Foundation SA. Conflict of Interest No. Aim To examine the health outcomes of 2,483 children first exposed to blue asbestos at Wittenoom when they were less than 16 years of age. Methods Standardised Mortality Ratios (SMR's) calculated to compare Wittenoom children's mortality with the Western Australian population. Results About 1,204 females and 1,279 males were children at Wittenoom, mean age of arrival 4 years (SD 4 years); 419 (17%) were born there or moved there soon after birth. Median duration of residence was 19 months (IQR 7-41 months). There were 228 deaths (75 females and 153 males) between 1950 and end of 2006. 40 deaths were from malignant mesothelioma (17% of all deaths -12 females, 28 males, -39 pleural, 1 peritoneal). Among males, there was excess mortality from all causes (SMR = 1.89), all cancers (SMR = 3.70), MM (SMR = 73), accidents, injuries and poisonings (SMR = 1.54) and circulatory disease (SMR = 2.21). Mortality from suicide and transport accidents were also in excess but not statistically significantly increased. Among females there was excess mortality from all causes (SMR = 1.62), and all cancers (SMR = 2.25) and MM (SMR = 155). Conclusion Former children of Wittenoom experience high cancer mortality. Support NHMRC. Nomination Nil. Conflict of Interest Nil.

Introduction Blue asbestos (crocidolite) was mined and milled at Wittenoom between 1943 and 1966 . Tailings from the mine were distributed and used extensively throughout the town. Exposure to children also occurred from the laundering of workers clothes at home. Earlier work has shown a lower risk of malignant mesothelioma (MM) in children from Wittenoom than in those exposed to blue asbestos as adults.A case report of a 69 year old ex-forestry worker with an 80 pack year smoking history is presented. He was referred with two distinct periods of hemoptysis, one 7 months prior to referral for which he declined investigation or follow up, and another three weeks prior to referral. On each occasion, he described two tablespoons of hemoptysis daily lasting approximately 1 month. He lives on an acreage at Mt Kilcoy, 94 km north of Brisbane, with his wife, one goat, three dogs, one cat, 51 deer and wild birds. Emphysema manifesting as gradually worsening exertional dyspnoea with wheeze, had been diagnosed years ago by his local doctor. He described symptoms of obstructive sleep apnoea including witnessed apnoea, choking arousals and loud snoring. He also reported intermittent diarrhoea for 2 years but denied weight loss or rectal blood or mucous. A CT chest showed multiple bilateral nodules of varying size the largest being 3.6 cm, and multiple low density liver lesions. The provisional diagnosis was metastatic colorectal cancer. Bronchoscopy with EBUS guidance did not yield the diagnosis which was eventually made by trans-thoracic needle aspiration without complication. Echinococcus serology performed post procedure was >1024, consistent with echinococcus infection. This case of echinococcus disease is presented and the vectors discussed. Echinococcus disease was previously prevalent in Australia and New Zealand, with a reduction in incidence from improved animal husbandry. With an increasing deer population in South East Queensland and subsequent rising human contact, clinical awareness is necessary to avoid potential complications from biopsy and ensure cases are promptly treated rather than mistakenly diagnosed as incurable disease. Introduction Community-acquired pneumonia (CAP) is a leading cause of mortality, morbidity and hospital admission places strain on our healthcare system. Procalcitonin (PCT) is a biomarker of bacterial infection which may help gauge the severity and prognosis of patients with CAP. Aim To examine the role of PCT measurement in reducing hospital admissions, length of stay (LOS), and antibiotic (AB) usage in patients with CAP. Methods Prospective, single-blinded, externally controlled study of consenting adult patients admitted with CAP. PCT levels were obtained on day 1 and day 3 (if indicated). The investigator evaluated clinical parameters and the PCT values to determine the timing of oral AB switch and discharge. This process was used to compare with standard practice but was not actually implemented for the purpose of this study. Results Sixty patients were included in the study. The mean age was 66.5±21.2y and 56.3% were male. The average PSI was 91 ± 40 (Class IV) and the median CURB-65 was 2. The mean LOS for this cohort was 5.32±4.56 d and the calculated LOS using PCT guidance pathway was 3.68±2.81 d. (p = 0.00006) A multivariate analysis will be presented. Conclusions Our study supports the hypothesis that the incorporation of PCT levels can reduce the requirement for hospital admission and LOS in patients with CAP. A randomised prospective clinical trial is planned to help clarify these findings. Support Nil. Introduction Children in the highlands of Papua New Guinea (PNG) suffer on average 4.3 acute lower respiratory infections (ALRIs) before age 18 months, 1/3 of which are moderate or severe. While Streptococcus pneumoniae and Haemophilus influenzae are the primary bacterial cause of ALRI in PNG, the role of viruses in the aetiology of ALRI is uncertain. Aim Determine identification rates of respiratory viruses in nasal samples collected from children with moderate/severe ALRI and healthy children aged <18 months in PNG. Methods As part of a neonatal pneumococcal conjugate vaccine trial in the PNG highlands, we collected pernasal swabs from children with moderate/severe ALRI (n = 49) and at routine follow-up (n = 48). RT-PCR methods were used to identify a broad range of respiratory viruses. The frequency of viral detection was compared between groups of samples collected during an ALRI and routinely using Chi-square analysis. Results Several viruses were detected more frequently in ALRI than routine samples: adenoviruses 33.3/12.5 (% of ALRI samples positive/% of routine samples positive) p = 0.032, influenza viruses 22.5/7.9 p = 0.023 and respiratory syncytial virus (RSV) 8.2/ 0.0 p = 0.043. Human metapneumovirus and parainfluenza viruses were detected in four and three samples, with no difference between groups. Human coronaviruses and human rhinoviruses (HRV) were less commonly detected in ALRI than in routine samples (4.2/8.3 p = 0.042 and 57.1/72.3 p = 0.178, respectively). A total of 62 different HRV strains were identified. Conclusion In young children in PNG, viral identification rates are high, with RSV, adenoviruses and influenza viruses associated with moderate/severe ALRI and a large amount of genetic diversity of rhinoviruses in both sick and healthy children. Introduction To increase the documentation and documented provision of an electronic Asthma Action Plan (e-AAP) to children discharged with asthma from the Emergency Department (ED) at CHW. Methods An electronic AAP (e-AAP) was introduced in April 2008 by a multidisciplinary team comprising representatives. At CHW, AAPs were available to be printed off by the intranet. To be entered into the electronic medical record (eMR), the medical officer had to photocopy the completed plan which would then be scanned into the eMR. Evidence suggested that busy doctors, particularly in the ED, were either not providing patients with AAPs on discharge or not photocopying them for the medical record. The evaluation of the e-AAP consisted of a review of the documented provision of asthma action plans in the hospital wide eMR (Powerchart) for a year pre & post the introduction of the e-AAP, a review of patients discharged from the ED with a diagnosis of asthma for similar six month periods pre and post intervention and a medical staff satisfaction survey. Results The total number of plans recorded in eMR increased by 816%, from 2007-2008 to 2008-2009 . The number of plans recorded for ED discharges increased significantly from 2% to 73% [p < 0.001]. The number of patients recorded as leaving the ED with a plan increased significantly from 20% to 79% (p < 0.001). The use of the e-AAP in the ED is now standard of care and this is also being adopted hospital wide as more staff became familiar with its usefulness.Conclusion The e-AAP significantly increased the number of recorded AAPs and patients discharged with a recorded AAP. Support Nil. Nomination Asthma/Allergy. Conflict of Interest No.

LISA WOOD 1,2 , MANOHAR GARG 2 , AMBER WOOD 1,2 , PETER GIBSON 1,2 1 Centre for Asthma and Respiratory Diseases, University of Newcastle, New South Wales, Australia, and 2 Nutraceuticals Research Group, University of Newcastle, New South Wales, AustraliaIntroduction Dietary fat activates innate immune responses, leading to an increase in systemic inflammation. However, the effect of dietary fat on airway inflammation has not been investigated. We hypothesised that a high fat intake may lead to increased airway neutrophilia in asthma. The aim of this study was to examine the effect of a high fat versus low fat food challenge on airway inflammation in asthma. Methods Non-obese subjects with asthma were randomized to receive a high fat/ high energy (HF) (n = 14) or low fat/ low energy (LF) (n = 16) food challenge. 16 obese subjects also received a HF challenge. Subjects on the HF challenge consumed a meal containing 4480 kJ, including 52% of energy (60 g) from fat. Subjects on the LF challenge consumed a meal containing 840 kJ, including 13% of energy (3 g) from fat. At baseline, hypertonic saline challenge and clinical assessment were performed. Induced sputum samples were collected at baseline and at 4 hours. Airway inflammatory markers included induced sputum total and differential cell counts, IL-8 and neutrophil elastase, measured by commercial assay. TLR4 mRNA expression from sputum cells was measured using RT-PCR. Results At 4 hours after the food challenge, subjects on the HF challenge, had a significantly higher increase in %sputum neutrophils (16.4 (4.4 (SEM)) % vs. 3.4 (4.1) %, p = 0.044) and higher fold increase in TLR4 mRNA expression (2.06 (1.3-5.4 (IQR)) vs. 1.00 (0.6-1.4), p = 0.037), compared to the LF challenge. Subjects on the HF challenge also had an impaired bronchodilator response, with a lower increase in FEV1/FVC% at 4 hours compared to the LF challenge (1.0 (-2.0-2.6 (IQR)) % vs. 4.5 (2.7-6.8) %, p = 0.001). There were no differences in the responses of obese vs. non-obese asthmatics to the HF challenge. Conclusions A high fat/ high energy challenge causes an increase in airway inflammation and suppresses bronchodilator response in asthma. Strategies aimed at reducing dietary fat intake may be useful in reducing inflammation in asthma. Support NHMRC project grant. Introduction Longitudinal FEV 1 data in children with non-cystic fibrosis (non-CF) bronchiectasis is contradictory and there is no multi-factor data on the evolution of lung function and growth in this group. We longitudinally reviewed lung function and growth in children with non-CF bronchiectasis and explored biologically plausible factors associated with changes in these parameters over time.Methods Fifty-two children with ‡3 years of lung function data were retrospectively reviewed. Changes in annual anthropometry and spirometry at year-3 and year-5 from baseline were analysed. The impact of gender, age, aetiology, baseline FEV 1 , exacerbation frequency, radiological extent and period of diagnosis was evaluated. Results Over 3 years, the group mean FEF 25-75 %predicted and BMI z-score improved by 3.01 (p = 0.04, 95%CI 0.14-5.86) and 0.089 (p = 0.01, 95%CI 0.02-0.15) per annum, respectively. FEV 1 %predicted, FVC %predicted and height z-score all showed non-significant improvement. Over 5 years, there was improvement in FVC %predicted (slope 1.74, p = 0.001) annually but only minor improvement in other parameters. Children with immunodeficiency and those with low baseline FEV 1 had significantly lower BMI at diagnosis. Frequency of hospitalized exacerbation and low baseline FEV 1 were the only significant predictors of change in FEV 1 over 3 years. Decline in FEV 1 %predicted was large (but nonsignificant) for each additional year in age of diagnosis. Conclusions Spirometric and anthropometric parameters in children with non-CF bronchiectasis remain stable over 3-5 year follow-up period once appropriate therapy is instituted. Severe exacerbations result in accelerated lung function decline. Increased medical cognizance of children with chronic moist cough is needed for early diagnosis, better management and improving overall outcome in bronchiectasis. Introduction It is well established that many survivors of very low birth weight (VLBW; <1500 g at birth) have impaired lung function. The aim of this study was to determine whether abnormal lung function at 25 years of age is established in childhood. A second aim was to see if abnormal lung function at 8 years of age tracks through the period of normal lung development to predict impaired maximal lung function and may be a precursor to COPD in adult years. Methods A cohort of VLBW (n = 210) and normal birth weight (NBW; >2500 g at birth; n = 60) has been followed for 25 years. Very Low Birthweight participants completed spirometry and lung volumes at 8, 11, 14, 18 and 25 years of age and NBW at 14, 18 and 25 years of age. Restricted maximum likelihood modeling was used for longitudinal FEV 1 z-score as it allows for analysis of data from different time points that are not necessarily evenly spaced, without being affected by missing data. Results About 137 VLBW children completed lung function testing at 8 years of age, 20 (14.6%) had abnormal FEV 1 z-scores (defined as >2 SD's below the mean). VLBW survivors showed minimal 'catch-up' in FEV 1 z-score over the 13 years of the study; those without (bronchopulmonary dysplasia) FEV 1 improved 0.034 (p = 0.014) z-scores, those with BPD FEV 1 improved 0.033 (p = 0.039) z-scores. VLBW with BPD survivors did not return to within normal limits. Conclusions The reduced lung function in adult survivors of low birth weight is established in early childhood. While there is some improvement in growth of those with abnormal FEV 1 z-scores in early childhood, those with BPD remain below two SD's from the mean, and at the age of 25 have a reduced peak lung function. Introduction Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Although there is evidence that individuals with a history of BPD have respiratory abnormalities in childhood, there remains a paucity of evidence regarding the outcome of the disease in adulthood. In a pilot study we recently described high resolution computed tomography (HRCT) appearances of emphysema in young adults with a history of BPD. Aims To describe the structural pulmonary sequelae of bronchopulmonary dysplasia in adulthood and to evaluate a scoring system originally designed for paediatric subjects. Methods About 51 adult survivors of BPD underwent HRCT of the chest, along with lung function testing (spirometry, lung volumes and diffusing capacity) and a respiratory health survey. The CT studies were scored by two thoracic radiologists blinded to the patient's clinical details, using a previously described system developed for children and adolescents who were born prematurely using 14 parameters. Results Abnormal findings were seen in all scans, the most common findings were subpleural triangular opacities (94%), linear opacities (90%), air trapping (65%) and emphysema (47%). Agreement between the two observers for total score and common abnormalities varied with a linear weighted kappa value of 0.18 for linear opacities, 0.71 for triangular opacities, 0.76 for air trapping, and 0.66 for emphysema. Conclusions Linear and sub-triangular opacities on HRCT chest are almost universal in young adults with a history of BPD. Findings of emphysema and gas trapping are common and there is good interobservor agreement for these abnormalities. Introduction Pulmonary surfactant (PS) is synthesised by alveolar type II epithelial cells to regulate the surface tension at the air-liquid interface of the air breathing lung. Developmental maturation of PS is controlled by many factors including oxygen, glucose, catecholamines and cortisol. The intrauterine growth restricted (IUGR) fetus is hypoxemic and hypoglycaemic, with elevated plasma catecholamines and cortisol. Aim To determine the impact of IUGR induced by chronic placental restriction via the carunclectomy model on PS maturation. Methods We investigated the expression of surfactant protein (SP) -A, -B and -C and their genes in lung tissue of fetal sheep at 133 days and 141 days gestation (term, 150 ± 3 days) from control and carunclectomised Merino ewes. Results Placentally restricted (PR) fetuses had a body weight <2 SD from the mean of control fetuses and a mean gestational PaO2 <17 mmHg. PR fetuses had a reduced absolute, but not relative lung weight, decreased plasma glucose and increased plasma cortisol concentration. Lung SP-A, -B and -C protein and mRNA expression were reduced in PR compared with control fetuses at both ages. SP-B and -C, but not SP-A mRNA expression and SP-A, but not SP-B or -C protein expression increased with gestational age. Mean gestational PaO2 was positively correlated with SP-A, -B and -C protein and SP-A and -C mRNA expression. SP-A and -B gene expression were inversely related to plasma cortisol concentration. Conclusion Chronic placental restriction and hypoxemia results in an inhibition of PS maturation and thus IUGR fetuses are at risk of lung complications, especially if born prematurely. Support by The ARC & NHMRC. Nomination Nil. Conflict of Interest Nil.

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Sue JENKINS 1,2,3 , Nola CECINS 1,2,3 1 Sir Charles Gairdner Hospital, Perth, Western Australia, Australia, 2 Curtin University of Technology, Perth, Western Australia, Australia, and 3 Lung Institute of Western Australia, Perth, Western Australia, AustraliaIntroduction The 6MWT is widely used to assess patients with chronic lung disease (CLD). Anecdotal reports and studies in small numbers of patients suggest that adverse events associated with the 6MWT are rare in patients with CLD. This study reports observed adverse events and predictors of oxygen desaturation during the 6MWT in patients with stable CLD referred to an out-patient pulmonary rehabilitation service. Methods About 741 consecutive patients completed the 6MWT in accordance with a standardised protocol that included continuous monitoring of oxygen saturation (SpO 2 ) and heart rate (HR, Polar). The respiratory diagnoses of the patients were chronic obstructive pulmonary disease (COPD), n = 565 (76%); interstitial lung disease (ILD), n = 84 (13%); bronchiectasis, n = 46 (6%) and asthma n = 39 (5%). Results Observed adverse events occurred in 43 tests (6%). One test was terminated when the patient reported chest pain and one patient developed persistent tachycardia (HR > 200 bpm) immediately following the test. In 35 tests (5%), the tester instructed the patient to stop walking due to profound oxygen desaturation (SpO 2 <80%). Six patients prematurely terminated the 6MWT due to intolerable symptoms. Forty-seven per cent (n = 345) of patients demonstrated oxygen desaturation, defined as a decrease in SpO 2 ‡4% to <90% during the test. Pre-exercise SpO 2 was a significant predictor of desaturation in the COPD (1.79, 1.54 to 2.08, adjusted odds ratio [OR], 95% confidence intervals) and ILD (OR 1.40, 1.11 to 1.77) cohorts with FEV 1 also a predictor in patients with COPD (OR 3.02, 1.77 to 5.15). Conclusions Profound oxygen desaturation is the commonest adverse event observed during the 6MWT in patients with stable CLD. This finding questions the American Thoracic Society guidelines for the 6MWT which state that oximetry is optional. Introduction There is weak support for use of opiates in palliation of refractory dyspnea; respiratory depression is perceived as a major risk. We evaluated the effect of i.v. morphine on dyspnea in controlled conditions and related this to concomitant respiratory depression. Methods With ethical approval, 6 healthy subjects received 0.07 mg/kg morphine sulphate or saline on separate days in a randomised controlled design. Before and for 2 hours after administration, subjects performed (i) dyspnea responses (measured with a Visual Analog Scale) to increasing P ET CO 2 with ventilation () constrained at resting levels (ii) Unconstrainedresponses to increasing P ET CO 2 to assess respiratory drive. Results Pre morphine with constrained , all subjects tolerated an elevated P ET CO 2 of 50-55 mmHg; mean dyspnea rating was 56% (7(SEM)). Post morphine, at the same P ET CO 2 , mean dyspnea rating fell to 29 % (5, p < 0.05, paired t). All subjects reported reduced dyspnea at 20 minutes and this was sustained for 2 hours. No changes in dyspnea scores were seen following saline. With unconstrained, at equivalent levels of P ET CO 2 , morphine, but not saline, was associated with a lower in each subject for up to 2 hours; mean fell from 30 (3) to 22 (2) l/min (p < 0.05). To assess if respiratory depression could account for reduced dyspnea, scores were compared at the different P ET CO 2 levels that induced equivalent unconstrainedlevels with and without morphine; mean dyspnea scores were not different (54 (10) vs. 52 (10) %). Conclusion A clinically moderate dose of morphine results in substantial and sustained relief of laboratory dyspnea in a small group of healthy subjects consistent with the associated degree of respiratory depression. Support Breathlessness Research Charitable Trust UK; NIH, USA. Nomination Nil.

Introduction Pulmonary rehabilitation (PR) is a cornerstone of management for patients with chronic obstructive pulmonary disease (COPD) and its efficacy is supported with Level 1 evidence. Despite the known benefits of PR, up to one third of those people with COPD who are referred to PR choose not to participate. There is little information regarding perceived barriers to attendance in an Australian health care context. Methods Nineteen people with COPD (10 women and nine men, GOLD stage I-IV, age range 53-86 years) who had declined to take part in an outpatient PR program at a metropolitan teaching hospital participated in a qualitative study. Semi-structured interviews were used to establish reasons for failing to attend the PR program. These interviews were transcribed verbatim and analysed using the principles of grounded theory. Results Three major themes were identified regarding barriers to attendance at PR. The first related to difficulties with getting there, including a lack of available transport and poor mobility. The second theme related to a lack of perceived benefit, including perceptions that PR would not improve their health or that they were currently doing enough exercise. The third major theme involved restrictions imposed by underlying medical conditions and included the influence of comorbidities and pain. Minor themes that arose included competing demands, age, fatigue and program timing. Conclusions In Australia many patients with COPD who are invited to attend PR do not perceive the program would be beneficial, feel they are too unwell to attend or have difficulty with access. Further support should be offered to PR candidates and alternative methods of delivering PR to enhance uptake should be considered. Introduction Pulmonary rehabilitation has emerged as recommended standard care for people with chronic lung disease. However potential demand to access these services far exceeds the available resources. This study's aim was to determine if baseline measures of the BODE Index, dyspnea (Modified Medical Research Council questionnaire), 6 minute walk distance (6MWD), physical activity, Taunton Respiratory quality of life questionnaire (TRQ), smoking status, and frequency of hospitalisations can predict responders to pulmonary rehabilitation. Methods We retrospectively evaluated all participants with a diagnosis of COPD, who attended the pulmonary rehabilitation program at the Prince Charles Hospital between 2004 and 2007. A participant was considered a responder to pulmonary rehabilitation if benefit was achieved in exercise capacity ( ‡20% increase in 6MWD) and/or quality of life ( ‡0.5 SD decrease in TRQ as described by Cohen's Effect Size). Prediction of responders was assessed using chi square cross tabulations and t-tests with significant measures analysed using a binary logistic regression model. Results One hundred and forty-two participants (76 males, mean age 69 (9 SD) years, mean FEV1 50.4 (20.3) %) who completed pulmonary rehabilitation were analysed. Sixtyfive (47.8%) people were categorised as responders using the above criteria. Significant mean differences were: TRQ 40.9 (25.2) for responders vs. 18.5 (16.3) for non-responders p < 0.001; BODE Index 3.4 (2.4) vs. 2.5 (1.7) p = 0.02; 6MWD 368 (123) m vs. 422 (96) m p = 0.004. The binary logistic regression model showed a higher TRQ score was the only factor that predicted a responder to pulmonary rehabilitation. No other measure added to the predictive power of the model. Conclusion Higher TRQ scores may be useful in predicting which participants are most likely to benefit from referral to pulmonary rehabilitation. Further study is underway investigating other factors that may improve these findings. Support Nil. Nomination Nil. Conflict of Interest No.