key: cord-0042033-kezgvn4q
authors: nan
title: TSANZ Oral Presentations
date: 2018-03-14
journal: Respirology
DOI: 10.1111/resp.13267
sha: 5b6cdf01c0558e1ef1e62318c2e6ded1627eb11e
doc_id: 42033
cord_uid: kezgvn4q

nan

significant cause of death in Australia but access to Palliative Care is limited. In addition, previous studies indicate that patients with chronic lung disease are more likely to have their first encounter with palliative care in a critical care setting.

Aim: Cabrini Hospital developed a shared model of early referral and access to palliative care for patients with advanced COPD integrated across the Respiratory Continuing care program and Palliative Homecare team, through: Enabling patients to live as actively as possible with focus on quality of life; Reducing time in hospital and optimizing utilization of continuing care services to support preferred place of care; Optimizing function and comfort physically, psychosocially, emotionally and spiritually; Minimizing physical and psychosocial symptoms.

Providing adequate knowledge and open communication for patients and carers to help timely and informed decision-making; Supporting carers throughout the person's illness; and Supporting patients and carers when death is inevitable and through the bereavement period.

Preliminary Results: Patient and families reported positive patient experience; improvement in preferred place of death; patients did not feel abandoned or "handed over' to another service; family end of life experience improved due to patient and family being well known to palliative homecare staff and respiratory nurses ; direct admission to inpatient palliative care services prevented a visit to emergency; prevention of hospital admission during final year of life improved quality of life; reduction in emergency calls to ambulance service due to breathlessness and anxiety;

Conclusion: A shared model of early referral and access to palliative care markedly improved quality of services for patients with advanced, non-malignant lung disease. Training is required to support palliative homecare nurses to deliver care to patients with non-malignant disease, and equally for chronic disease nurses to support and deliver a palliative care approach. ical utility is emerging with this commercial equipment but the prognostic value of performing preschool MBW (defined as age 2-6 years) remains unclear. We have previously shown an association between higher preschool Lung Clearance Index (LCI) values and greater medication use and incidence of bacterial isolation within our clinic. This study aimed to explore the association between those preschool LCI values and later spirometry, a well established clinical tool in older CF subjects.

Methods: Current spirometry values (FEV 1 , FEV were collated on the original 37 preschool children who had MBW performed at mean (SD) age 5.0 (1.2, range 2.8-6.9) yrs: median (range) LCI 8.0 (6.5-14.3) . Spirometry results were expressed as z-scores (GLI reference equations). Abnormal preschool LCI was defined based on recently published preschool healthy control data using identical equipment and testing protocol 1 (ULN for LCI 8.0).

Results: Technically acceptable spirometry data were available in 35/37 (95%) (one had moved out of state, one has autism) at mean (SD; range) age 7.7 (1.4; 4.8-9 .8) years, which was 2.7 (0.4; 1.0-3.3) years after the original MBW testing time point.

Later spirometry (z scores) Results: 23 children (9F; 17 with SMA II, median age 108 months)

were included. Median FVC% predicted (z score) was 61% (n=19, -3.32); Rrs 8 z-score: 2.19 (n=11); Xrs 8 z-score: -2.03 (n=11); SNIP z-score: -2.53 (n=10) & LCI: 7.36 (n=12). Median (IQR) REM related Apnea-hypopnea index (rAHI) was high at 5.9 (2.9-17.5;n=19). 10 children (9 with SMA II) required long-term nocturnal NIV initiated at a median age of 94 months; 5 (50%) after an acute respiratory illness. These children were older (127 vs 84 months; p=0.03) with significantly worse FVC-z scores (-4.8 vs -1.18; p<0.01); rAHI (26.5 vs. 4.2; p=0.05), LCI (8.8 vs. 7.1, p=0.01) & SNIP z-scores (-3.5 vs. -1.47 p=0.001). Predictors of NIV need will be analysed using a logistic regression model once the prospective arm is completed.

Conclusion: Most children with SMA II need nocturnal ventilatory support beginning in early childhood and FVC may be a predictor. FOT, SNIP and LCI were deranged and may help in predicting early respiratory insufficiency, particularly in early years. School of Human Sciences (Physiology), The University of Western Australia, Perth, Australia, and 2 Centre for Neonatal Research and Education, School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia Introduction/Aim: Chorioamnionitis is associated with preterm birth and the development of airway disease in later life. Chorioamnionitis promotes lung inflammation, but its effect on airway smooth muscle (ASM) function is unknown. Postnatal steroids are given to preterm infants with severe lung disease and may have beneficial effects on airway development. This study examined the separate and combined effects of chorioamnionitis and postnatal steroids on ASM contraction in a preterm ovine model.

Methods: Chorioamnionitis was induced by ultrasound-guided intraamniotic (IA) injection of lipopolysaccharide (LPS) into time-mated ewes (127d gestation; term=150d). Postnatally, LPS-exposed lambs received intravenous low-dose dexamethasone (LPS/Dex) or saline (LPS/Sal: n=6) commencing within 2 h of birth. Postnatal controls received IA saline at 127d gestation and daily intravenous low-dose dexamethasone (Sal/Dex: n=9) or saline (Sal/Sal: n=6) postnatally. Lambs were delivered via caesarean section at 129d gestation, receiving respiratory support as required, and euthanised after 7d (i.e., 136d postconceptional age). A fifth group of naïve fetal control lambs were euthanised immediately at 136d gestation as maturational controls. Bronchial rings were studied in organ bath chambers. Isometric force production to acetylcholine was measured and dose-response curves constructed to determine maximal response, slope and sensitivity. ASM thickness was determined histologically after Masson's Trichrome.

Results: Maximal response, slope and sensitivity were similar between maturational and postnatal (placebo) controls, indicating ASM contraction was unaffected by preterm delivery. Maximal response was increased by IA LPS administration (p<0.05) and not significantly affected by postnatal dexamethasone. Dose-response slope was reduced by postnatal dexamethasone (p<0.05) in LPS-exposed lambs. ASM thickness was lower in animals treated postnatally with dexamethasone, irrespective of prior exposure to LPS (p<0.05). asthma but its efficacy is limited by β 2 -adrenoceptor desensitisation. Free fatty acid receptors 1 and 4 (FFAR1, FFAR4) are expressed in mouse and human lungs (Mizuta et al., AJP Lung, 2015) and their agonists cause relaxation of mouse airways with greater efficacy than salbutamol (Bourke et al., AJRCMB, 2017) .

Aims: To compare bronchodilation to salbutamol, GW9508 (FFAR1/ FFAR4 agonist) and TUG891 (FFAR4 agonist) under conditions of β 2adrenoceptor desensitisation, test potential FFAR1/FFAR4 desensitisation and assess FFAR expression in mouse airways from a model of chronic allergic airways disease and human airways from subjects with and without asthma.

Methods: Precision cut lung slices were prepared from 6-8-week-old male BALB/C mice. Airway relaxation to GW9508, TUG891, and salbutamol were compared after overnight incubation with 10μM salbutamol, 100μM GW9508, or vehicle. Immunohistochemistry for FFARs was performed on lung sections from saline control (C) and ovalbumin (OVA)sensitised mice and airway biopsies from non-asthmatic (NA) and asthmatic (A) subjects.

Results: Salbutamol and FFAR agonists relaxed airways precontracted with methacholine (%relaxation: 10μM salbutamol 50AE6%; 100μM GW9508 28AE7%; 100μM TUG891 44AE10%, n=7, 4, 6) . Overnight incubation with salbutamol reduced subsequent relaxation to salbutamol (to 4AE2%, n=7, p<0.0001 cf control), but not to GW9508 or TUG891 (27AE6%, 42AE10% respectively, n=6,5). GW9508 incubation did not affect salbutamol-or GW9508-mediated relaxation (44AE6%, 26AE7% resepectively, n=6, 6) . Both FFAR1 and FFAR4 expression was similar in C and found a single bout of moderate-intensity exercise decreased exhaled nitric oxide in physically inactive, but not in physically active, adults with asthma. The aim of this study was to examine the acute effects of exercise intensity on airway inflammation in adults with asthma, and to examine whether this differs by usual exercise levels.

Methods: In a randomised controlled trial, adults with asthma were randomised to complete either 45 minutes of moderate-intensity exercise (55-70% HRmax) on a cycle ergometer (n=19), 30 minutes of vigorousintensity exercise (70-85% HRmax) on a cycle ergometer (n=19) or 30 minutes of rest (n=18). Sputum cell counts were obtained the day prior to and 4 hours-post exercise/rest.

Results: Sputum eosinophil count was lower following moderateintensity exercise [0 (-26, 23]x10 6 /mL) versus rest [9 (3, 42)x10 6 /mL, p=0.0249]. However, sputum eosinophil count did not change following vigorous-intensity exercise [8 (-21, 47)x10 6 /mL, p=0.380] versus rest. Participants who reported performing exercise causing breathlessness or sweating ≤once per week had a significant decrease in sputum eosinophil count [-3 (-89 , 0) vs 7 (3, 142)x10 6 /mL, p=0.006] and sputum %eosinophils [-0.3 (-0 .7, 0)% vs 0.5 (0.1, 2.0)%, p=0.012] following moderateintensity exercise, compared to rest. Participants who became breathless or sweaty during exercise ≥twice/week had no change in sputum eosinophil count (p=0.395) or sputum %eosinophils (p=0.449) following the exercise challenge.

Conclusion: This study demonstrates that an acute bout of moderate-intensity, but not vigorous-intensity, exercise reduces sputum eosinophils in adults with asthma. This change was only evident in physically inactive participants, suggesting that regular physical activity may protect against airway inflammation. Methods: Randomized, double-blind, placebo-or active-controlled studies of VX-440 and VX-152 (phase 2), and VX-659 (phase 1) in TC were conducted in CF patients with F508del/MF (n=80) or F508del/ F508del genotypes (n=40; the latter with VX-152 and VX-440 only; after 4 weeks of TEZ/IVA pretreatment). Primary objectives were safety and tolerability; efficacy and pharmacodynamic effects were assessed by absolute change in ppFEV 1 and sweat chloride from baseline, respectively.

Results: Baseline characteristics were balanced. NG TC regimens were well tolerated; most adverse events (AEs) were mild or moderate. AEs leading to discontinuation included increased alanine aminotransferase/aspartate aminotransferase (VX-440 TC, n=1), pneumonia (VX-152 TC, n=1), and respiration abnormal/sputum increased (placebo, n=1). After 2 to 4 weeks, significant improvement from baseline in ppFEV 1 of 9.6 to 12.0 percentage points was seen with all 3 NG TC regimens in F508del/MF patients, and significant improvement from baseline of 7.3 to 9.5 percentage points was seen with VX-440 or VX-152 TC on top of TEZ/IVA in F508del/F508del patients (vs TEZ/IVA baseline). Significant reductions from baseline in sweat chloride were also seen with TC regimens vs placebo or TEZ/IVA alone.

Conclusion: This is the first demonstration of substantial improvements with NG TC regimens in patients with CF with F508del/MF genotype, in whom previous CFTR modulators have failed, and in patients with CF with F508del/F508del genotype. Ongoing studies will guide development of TC regimens.

Introduction: Cystic Fibrosis(CF) results in insulin deficiency from birth and progresses to Cystic Fibrosis-related diabetes (CFRD) [1] . CFRD has a significant impact on lung function, respiratory infections, and nutrition, and leads to an increase in mortality [2] . However, the prevalence of early hyperglycaemia and impact on respiratory tract infections in young children with CF remains unknown.

Aims: To determine the prevalence of hyperglycaemia in children with CF using Continuous Glucose Monitoring (CGM) To correlate hyperglycemia on CGM with presence of CF pathogen and neutrophil percentage in routine bronchoalveolar lavage (BAL).

Methods: A single-centre study of children with CF <5years. The CGM device (CGM Medtronic MiniMed) was inserted when clinically well during routine bronchoscopy/BAL and worn for 3 days. CGM outcomes included peak glucose, time spent >7.8mmol/L and Area Under Curve (AUC) >7.8mmol/L. BAL samples were cultured and cell count and differential determined. A t-test and regression analysis was undertaken to examine the relationship between hyperglycaemia and the presence of CF pathogen, and neutrophil percentage on BAL.

Results: 14 children (3 female) had CGMs performed, 12/14 had neutrophil percentage results available. Median age 2.44 years (range 1-5.5 ). 3 day glucose mean=5.89AE0.49mmol/L (meanAE SD). 43% (6/14) had diabetic range (≥11.1mmol/L) glucose levels. Participants who had positive cultures spent a greater period of time >7.8mmol/L on CGM (mean time 9.9%) compared with culture negative participants (3%, p=0.02), and had a greater glucose AUC>7.8mmol/L (p=0.04). There was a positive correlation with peak glucose (r 2 =0.4, p=0.02) and AUC>7.8mmol/L (r 2 =0.4, p= 0.04) with neutrophil burden on lavage.

Conclusion: Young children with CF have demonstrated diabetic range hyperglycaemia on CGM. CF pathogens are more likely to be present when glucose abnormalities are more severe and a significant correlation between neutrophil count and hyperglycemia was demonstrated. Further research is underway to determine whether abnormalities on CGM in this cohort has an impact on nutrition, pulmonary inflammation and lung function.

Introduction/Aim: The Imaging and Medical Beamline (IMBL) at the Australian Synchrotron was designed to be the world's widest synchrotron x-ray beam, to facilitate clinical imaging and therapeutic applications in humans, as well as for imaging large animal models. Our group is currently interested in imaging the airways of newly-developed CF animal models that display human-like lung disease, such as the CF pig. We hypothesise that the ability of the lung to clear inhaled particulates by mucociliary transit (MCT) can be used as an outcome measure for assessing the effectiveness of CF airway therapies. This study extends findings from ex vivo sheep and pig tracheal tissue studies previously performed at the IMBL, and was designed to determine whether the design of the IMBL is suitable for imaging pig airways.

Methods: A small sample of 200 μm diameter high refractive index (HRI) glass bead marker particles were delivered into the tracheal airway surface of eight live piglets. Automated analysis algorithms were used to track and quantify deposited-particle motion, including the response to aerosol delivery of hypertonic saline. A high-resolution computed tomographic (CT) whole-animal post-mortem scan of one pig was also performed to verify the large-sample CT capabilities of the IMBL.

Results: MCT tracking particles were visible in all animals, and our automated MCT tracking algorithms were able to identify and track particles. A CT of the whole animal was successfully acquired, and visualisations were successfully made from the CT dataset. Due to unexpected IMBL technical and equipment issues shuttering of the X-ray bean was sometimes poorly controlled, resulting in high radiation doses for some animals.

Conclusion: This study demonstrated that the IMBL is suitable for large animal tracheal MCT imaging and CT. Radiation doses must be carefully and reliably controlled for future non-recovery studies, and will enable estimation of the minimum achievable doses with this experiment design.

Medical Imaging, St Vincents Hospital, Fitzroy, Australia, 11 Medicine, University of Tasmania, Hobart, Australia, and 12 Royal Prince Alfred Hospital, Camperdown, Australia Introduction/Aim: Idiopathic Pulmonary Fibrosis(IPF) is a progressive scarring lung disease of unknown cause with limited treatment and a median survival of 2-3 years. Our aim was to identify potential occupational and environmental exposures associated with development of IPF in Australia.

Methods: Cases were recruited by the Australian IPF registry.

Patients completed a questionnaire about demographics, smoking, family history, environmental and occupational exposures, and medical history.

Clinical, radiological and histopathological data were reviewed by a multidisciplinary panel. Population based controls were recruited by random digit dialling, frequency matched on age, sex and state, and interviewed to collect comparable data. Multivariate logistic regression was used to assess associations with IPF as Odds Ratios(OR) and 95% confidence intervals(95%CI), adjusted for age, sex and smoking.

Results: Data were from 374 cases assessed by multidisciplinary discussion as definite, probable or possible IPF, and 902 controls. The meanAESD age of cases was 71.2AE7.8 and controls 70.8AE8.4 years. 72% cases and 69% controls were male. Current or past tobacco smoking was associated with increased risk of IPF: OR=2.24 (95%CI 1.72, 2.91), but marijuana use appeared protective: 0.43 (0.26, 0.70). A family history of pulmonary fibrosis was associated with 14.1 (7.14, 27.9) fold increased risk of IPF. No domestic environmental exposures were associated with increased risk, but pet birds or standing water appeared protective (OR=0.51; 0.34, 0.78 and 0.57; 0.36, 0.89 respectively). Self-reported occupational exposure to asbestos was associated with increased risk: OR=1.38 (1.06, 1.79) , but silica appeared protective: 0.60 (0.42, 0.85). Self-reported occupational exposures to gases, fumes, chemicals or dust were not associated with IPF.

Conclusion: Preliminary findings suggest that the burden of IPF could be reduced by continued tobacco control measures and preventing ongoing exposure to asbestos. More detailed assessment of occupational exposures will be undertaken using the Finnish job exposure matrix Alliance for Research in Exercise, Nutrition and Activity (ARENA), Sansom Institute, School of Health Sciences, University of South Australia, Adelaide, Australia, and 2 School of Health Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia Introduction/Aim: Longitudinal surveillance of firefighter lung function is highly valuable, especially considering its utility in determining changes in function following disastrous exposures. Studies investigating the long-term rate of change in lung function parameters of firefighters, however, have produced mixed findings. We aimed to determine the rate of change in FEV 1 and FVC of a contemporary cohort professional South Australian Metropolitan Fire Service (SAMFS) firefighters.

Methods: Spirometry was conducted in 5 stages between 2007 and 2016 on all available and consenting full-time firefighting staff, in accordance with ATS/ERS criteria using a Viasys MasterScreen ® spirometry system. We examined serial FEV 1 and FVC measurements to determine the average rate of change using linear mixed effects modelling.

Results: Participation at each stage of data collection ranged from approximately 48-64%. Data from 838 individual male firefighters, each contributing an average of 2.6 AE 1.1 (range 1-5) measurements, were included in the analysis. Fifty per cent of included firefighters had at least three measurements. Preliminary analyses show that the proportion of firefighters below the lower limit of normal (LLN) at baseline was 0.7% for FEV 1 , 0.0% for FVC and 14.2% for FEV 1 /FVC, while longitudinally, FEV 1 (adjusted for baseline age and height) declined by 34 (95% CI, 30 to 37) mL/yr while FVC declined by 24 (95% CI, 20 to 29) mL/yr.

The SAMFS firefighters observed in this study showed normal levels of FEV 1 and FVC at baseline; unsurprising given that they are selected, in part, based on their physical fitness. Early results indicate that the cohort have a normal rate of change in FEV 1 and FVC, suggesting that their lung function remains relatively unaffected by their occupation. Indigenous children and young adults (aged 3 to 25 years) from seven Queensland communities. Questionnaires and medical charts were reviewed to identify healthy participants (no respiratory and/or atopic illness ever).

Results: Acceptable FeNO measurements were achieved by 553 children (≤12 years) and 288 adults (>12 years). Participants with a history of respiratory and/or atopy conditions were excluded resulting in a healthy cohort of children (n=401, 72.5%) and adults (n=193, 67%). The geometric mean FeNO results for children and adults were 11.1ppb and 12.5ppb respectively. Table 1 summarises the distribution of healthy FeNO results for each ethnic group according to current cut-off ranges.

Conclusion: Although the majority of participants had FeNO results within the age-respective normal ranges, we found a proportion of healthy participants with elevated FeNO results in all groups. The greatest proportion of elevated results was seen in Torres Strait Islander children and adults, and Aboriginal/Torres Strait Islander children. This suggests that the recommended cut-off ranges may not be appropriate for these groups. Further investigation is still needed. Aim: To analyse the efficacy of LDCT in detection of lung cancer in an asbestos-exposed population over a 5-year period.

Methods: In 2012, the Asbestos Review Program (based at Sir Charles Gairdner Hospital) began performing annual LDCT to screen an asbestos-exposed population for asbestos related lung disease and lung cancer. Population: Wittenoom miners and residents, other individuals with >3 months cumulative full time exposure. All participants had a prone LDCT scan with annual health questionnaire (including smoking status), spirometry and gas transfer.

Results: 5907 LDCT scans were performed on 1760 individuals with a median age of 70 years (IQR 63-76), 1490 (85.1%) were male and 1115 (63.7%) were ever-smokers. Lung cancer was diagnosed in 17 participants (0.97% of the cohort), 15 (pre-operative stage 1a or b) underwent treatment with curative intent, 2 underwent non-curative chemo-radiation. Lung cancer was prevalent in 10 (59%), and incident in 7 (41%) individuals (see Table  1 ). One participant died 4 months after surgery (found to have M1a disease during operation); no participants treated curatively have had reoccurrence to date. Mesothelioma was diagnosed in 7 other individuals. Asbestosis was present in 40.3% of the ARP population and 64.0% had pleural plaques, confirming significant asbestos exposure. The median radiation exposure per LDCT was 0.20mSv (IQR 0.14-0.52).

Conclusions: A carefully controlled LDCT screening program is effective at diagnosing and treating early-stage lung cancer in this population. Occupational exposure to asbestos should be accounted for in assessing risk for lung cancer. Editorial material and organization © 2018 Asian Pacific Society of Respirology. Copyright of individual abstracts remains with the authors.

] parts per billion. Increasing exposure to NO 2 was associated with reduced T L co in a dose-response manner [p-for-trend<0.001]. Compared with the lowest quartile of NO 2 exposure, the reduction in T L co was equivalent to 7.7% of predicted for the highest NO 2 quartile (95%CI: −10.8 to −4.5) independent of smoking, and was significantly lower for those with current asthma [p (interaction) =0.005]. There was a trend to reduced TLC [pfor-trend=0.02], and reductions in post-BD FVC for non-and past but not current smokers exposed to the highest NO 2 quartile [non-smokers −2.6% pred, p=0.042, p (interaction) =0.056]. There were no statistically significant relationships with post-BD FEV 1 /FVC, FEF 25-75% or gas trapping (RV/TLC).

We provide evidence for a moderate adverse association between NO 2 exposure and T L co at relatively low pollution levels, that varies with current asthma status. Other non-obstructive features favour a lung parenchymal process, although co-existent small airway narrowing may be masked by reduced FVC levels. This new knowledge supports environmental policy to reduce NO 2 levels to as low as feasible. Introduction/Aim: Accelerated adult lung function decline is a major pathway to chronic obstructive pulmonary disease. We sought to investigate associations and interactions between life span factors and lung function decline during middle age.

Methods: Post-bronchodilator lung function was measured at 45 and 53 years in 842 participants from the Tasmanian Longitudinal Health Study. We used multivariate linear regression to investigate associations of factors in adulthood (current asthma, smoking, atopy, BMI, BMI change, occupational exposures and traffic related air pollution), childhood (pneumonia, asthma, parental asthma and parental smoking) and

Glutathione S-transferase gene polymorphisms, with the rate of lung function decline between 45 and 53 years. Interactions between factors were also investigated.

Results: Current asthma (-6; 95%CI: -11,-1 mL/year), current smoking (-16; -21,-10 mL/year), atopy (-5; -9,-0.7 mL/year), all at 45 years, lifetime occupational exposure to vapour/gas/dust/fumes (-6; -11,-1 mL/year) and increased BMI during the follow-up period (-2; -2.6,-1.5 mL/year per kg/m 2 increase) were independently associated with accelerated FEV 1 decline after controlling for age, height, sex, socioeconomic status and lung function at baseline (45 years). Current smoking (-12; -18,-6 mL/ year) and BMI change (-2.5; -3.2,-1.9 mL/year per kg/m 2 increase) were associated with greater FVC decline. GTTM1 polymorphism modified the effect of occupational exposure (p=0.06 and 0.07), and heavy maternal smoking during childhood modified the effect of personal smoking (p=0.03 and 0.02) on both FEV 1 and FVC decline. The effect of occupational exposure was only significant for carriers of the GSTM1 null genotype, and the effect of personal smoking was augmented in those also exposed to maternal smoking.

Conclusion: Lung function decline in this middle-aged sample was predominantly influenced by adult factors. Exposure to maternal smoking during childhood and genetic susceptibility may predispose people to being more susceptible to adulthood exposures. 

Introduction/Aim: Personal vaporizers ("electronic-cigarettes") aerosolise a liquid "e-juice" producing an aerosol which is inhaled. There is no regulation of e-juice ingredients. There are tens-of-thousands of different flavours, nicotine concentrations and excipient blends available from thousands of suppliers. Furthermore, while many ingredients are approved as food additives, inhalation toxicology data may be unavailable. We aimed to test the physico-chemical properties of a range of e-juices and aerosols to (i) identify potentially toxic substances and (ii) to see whether ingredients match labelling.

Methods: 18 e-juices were obtained from Australian and US retailers.

E-juice chemistry was analysed via GC-MS. Aerosols were generated using a custom-made device based on an Innokin MVP2 vaporizer / Innokin iClear30 cartomizers set at 2.1Ω and 4.2V. Aerosols were collected for 30 minutes using appropriate filters and collection tubes. We assessed levels of carbonyls, volatile organics, polycyclic-aromatics, nicotine, particulate matter and metals. Aerosol mass and size distributions were measured using an optical particle spectrometer.

Results: 28 different chemicals were detected in e-juices including known respiratory irritants such as 2-chlorophenol and 1,2,3-butantriol. Nicotine was detected in 6 apparently "nicotine-free" juices. Seven metals were identified in aerosols, including titanium, chromium and nickel. We also identified 7 carbonyls, however only formaldehyde, acetaldehyde and acetone were common. Sixteen volatile organics were identified. The solvents hexane and 2-ethoxy ethanol were ubiquitous in all samples. No poly-cyclic aromatics were detected. Aerosols contained particulate matter at hugely varying levels (3.3 to 63mg/m 3 ) and particle size distributions also varied considerably, apparently based on the excipient mixture.

The physico-chemical properties of e-juices and aerosols vary widely and hence their potential to impact health is also likely to vary. Importantly, nicotine was found in many "nicotine-free" juices, which has implications for addiction. Introduction/Aim: COPD is an incurable, progressive illness, with associated significant morbidity and mortality. Accurately determining prognosis in severe COPD is well-recognised to be challenging, as is diagnosing "active dying".

Aim: To audit the use of diagnostic tests in both recognising active dying and after establishing the "Goal of Care" (GOC) was palliation in COPD patients dying in hospital. Methods: General practices (n=43) were block-randomised into ICG (interdisciplinary care group) or UCG (usual care group). Patient participants with spirometry-confirmed COPD in UCG practices received routine care from their GP and Quitline referral, if appropriate. ICG participants received the RADICALS model of care, coordinated by a research assistant, GPs and staff at each clinic. The model comprised individualised smoking cessation support, a home medicines review (HMR) from a consultant pharmacist, and home-based pulmonary rehabilitation from specifically trained physiotherapists. The primary endpoint is change in Health Related Quality of Life (HRQoL), as measured by the St George's Respiratory Questionnaire (SGRQ), at 6 months from baseline. Other outcomes include changes in lung function, dyspnoea, COPD assessment test (CAT) score and EuroQol-5D at 6 and 12 months.

Results: A total of 275 patients with COPD were included -161 in ICG and 114 in UCG. Their mean (AESD) age was 64.4 (AE11.0) years; 171 (62%) were male and 168 (61%) were current smokers. Mean/ median baseline SGRQ, CAT and mMRC scores were 32.3 (AE18.2), 13.1 (AE7.8) and [1] [2] . A total of 85 ICG participants received the HMR, 71 completed home-based pulmonary rehabilitation, and 62 received both components. Six month follow-ups are complete (n=208); 12 month follow-ups are in progress and will be completed by February 2018.

Conclusion: An interdisciplinary model of care for COPD has been developed, implemented and evaluated in general practice. HMR and home-based pulmonary rehabilitation had moderate acceptance as interventions by GPs and patients.

Grant/in-kind support: NHMRC, Lung Foundation Australia, Boehringer Ingelheim, Eastern Melbourne PHN, Cyril Tonkin Scholarship Conflict of Interest: Funding was received from Boehringer Ingelheim. Boehringer Ingelheim was involved in project discussions, planning and progress review, but had no involvement in the design of the intervention program and will not be contributing to decisions regarding data analysis and dissemination of findings. Introduction: LFA undertook a survey to gain insight into the key issues facing consumers and carers, and to understand how LFA meetsor can better meettheir needs.

Methods: 9,000 surveys were distributed (via email and post) to consumers with any lung disease that subscribe to the LFA network.

Results: 1700 surveys were completed, representing a response rate of approximately 19%. Of these, 65% were female, 57% were aged between 65-79 years, 87% had a lung disease and 13% were carers.

Respondents indicated that 39% see family and friends less often, 29% feel isolated from society and 59% do the things they love less often because of their lung disease. When asked specifically about how they felt at time of diagnosis, 30% felt less deserving of help than people with other medical conditions, 23% felt shame, guilt or fear of being discriminated against, 41% felt stigmatised by the view that lung diseases are self-inflicted and smoking-related and 58% felt they had all the support they needed to deal with the diagnosis. Suggestions were received about additional LFA supports; responses highlighted the need for psychosocial support through more telephone, online and face-to-face connection with LFA and other consumers, as well as the need for additional education seminars and webinars, and more information on specific disease treatments and research.

Conclusion: People impacted by lung disease face many challenges. This survey has detailed the effect on community and social interactions, with feelings of isolation and less contact with loved ones highlighted. Also it demonstrates the shame, stigma and guilt some people may experience when diagnosed with a lung disease. Methods: Cultures of bronchial AEC (bAEC) lines, and from control and COPD donors differentiated at an air-liquid interface (ALI) were exposed to 10% cigarette smoke-extract (CSE) and NTHi. Markers of xenophagic flux and intracellular NTHi were assessed using western analysis, immunofluorescence and transmission electron microscopy (TEM).

Results: AEC exposed to 10% CSE exhibit a block in autophagic flux and down-regulation of the xenophagy-microbial adapter protein NDP52.

Immunofluorescence analysis resolved intracellular NTHi within AEC exposed to 10% CSE in proximity to the autophagic apparatus marker LC3. Importantly, control ALI cultures exposed to NTHi for 24h contained no detectable infection and evidence of normal autophagic activity, whereas COPD-derived bAEC contained multiple infective particles ( Fig.1) , some which remained intact within autophagosome-like vesicles. Further, TEM analysis demonstrated the expulsion of autophagosome-like vesicles.

Conclusion: NTHi is able to avoid xenophagic degradation in AEC exposed to 10% CSE or in cultures of COPD-derived AEC, and may usurp the defective autophagic apparatus as a mode of persistence and extracellular propagation. Hence, modes of therapeutic intervention which restore normal xenophagic activity in AECs will significant utility to improve the clearance of intracellular NTHi infection, and thereby decrease the influence of this damaging pathogen in the airways afflicted by COPD. Grant Support: Thoracic Society of Australia and New Zealand/ AstraZeneca NTHi, and considerable autophagic activity (evidenced by dark electron dense regions) within vesicular structures. Conversely, NTHi was readily evident in AEC derived from COPD donors and in close proximity to similar vesicular structures.

Respirology ( Introduction/Aim: Influenza is a significant global burden with 5 million cases per year, 10% of which are fatal and thus, there is an urgent need for new therapeutics. Toll like receptor 7 (TLR7) is a pattern recognition receptor, which drives a powerful anti-viral signalling pathway that helps clear virus infections. The aim of the present study was to determine the effect of the TLR7 agonist imiquimod on morbidity, lung inflammation, oxidative stress and antibody production caused by influenza A virus (IAV) infection in mice.

Methods: Saline or imiquimod (50μg/mouse) was delivered intranasally to anaesthetised male C57BL/6J mice one day (d-1) prior to infection with a low (10 3 PFU/mouse) or high dose (10 5 PFU/mouse) of the mouse adapted Hong Kong X31 virus strain and everyday thereafter until mice were culled day 3 (d3) or 7 (d7) post-infection for analysis. Bronchoalveolar lavage (BAL) was performed to assess airways inflammation, and inflammatory cell oxidative burst (by L-012 enhanced chemiluminescence). In addition, BAL fluid and serum was used to determine antibody titres. The lungs were then harvested and used to assess inflammation (H&E staining) and pro-inflammatory cytokine gene expression by qPCR. Bodyweights were recorded daily during the experimental process.

Results: Imiquimod significantly suppressed body weight loss caused by IAV infection with a maximum reduction of~60% starting from day 4 (d4) (10 3 PFU/mouse, n=7-13, p<0.001). At d3 post infection, imiquimod treatment caused a significant reduction (~50-60%) in airway and peribronchial inflammation and BALF neutrophil populations (10 5 PFU/mouse, n=8-15, p<0.01) but had no effect on macrophage and lymphocyte populations, and the oxidative burst. TNF-α and IL-6 mRNA expression was supressed by~60% (p<0.01 and p<0.05, respectively), whilst IFN-β and IL-1β mRNA expression were unaffected. Day 7 data showed a modest but significant increase in IgE, IgM, IgG1, and IgG2a (p<0.05) in BALF following imiquimod treatment compared to control. There were no changes in antibody titres within the serum.

Our findings highlight a potential of imiquimod as a therapeutic option for the treatment of influenza disease. there is a lack of understanding of host immunity during respiratory infection with CoVs. In this study, we characterised the innate immune responses of differentiated primary bronchial epithelial cells (pBECs) to infection with related less-virulent OC43-CoV and 229E-CoV.

Methods: Human pBECs were grown at the air liquid interface (ALI) until differentiation was observed (25-30 days), and infected at a multiplicity of infection (MOI) 0.1 with OC43-CoV or 229E-CoV for 0, 24, 96 hours and 7 days. Supernatants and RNA were collected to measure pro-inflammatory-and anti-viral-cytokines and viral replication. Using microarray, the gene expression profile of OC43-CoV and 229E-CoV infection was analysed (n=1). A549 cells transduced to overexpress Interferon-induced transmembrane proteins (IFITM) 1, 2 and 3 were infected with OC43-CoV or 229E-CoV. Viral replication was measured at 0, 8, 24 and 48 hours post-infection.

Results: OC43-CoV and 229E-CoV demonstrated different viral replication kinetics. 229E-CoV replicated earlier and more efficiently, peaking at 24 hours. This was associated with a delayed but robust activation of the innate host response, with induction of type I and III interferons (IFNβ, IFN-λ1/3), IFN stimulated genes and IP-10. In contrast, replication of OC43-CoV peaked between 96 and 168 hours, with attenuated levels of IFN-β, IFN-λ1/3 and IP-10. Microarray data also identified IFITM protein upregulation during 229E-CoV infection. In A549 cells over-expressing IFITM 1, 2 or 3, 229E-CoV replication was suppressed by IFITM 1 and 3, while the IFITM2 clone displayed similar replication kinetics to the control. OC43-CoV replication was unhindered by over-expression of all IFITM proteins.

Conclusion: This study demonstrated that both OC43 and 229E-CoVs replicated in differentiated pBECs, but they induce a divergent innate immune response potentially linked to their different replication kinetics. Understanding the host-virus interaction for these less virulent coronaviruses will give insight into pathogenic mechanisms underpinning SARS-CoV and MERS-CoV-induced respiratory disease. Results: In the acute model, TGFB was over-expressed for 2 days prior to IAV infection. These mice experienced more severe bronchitis and pneumonia, increased inflammatory cell infiltrates and enhanced cytokine and chemokine production in bronchoalveolar lavage (BAL) fluid compared to mice with normal TGFB levels. These mice also demonstrated a suppressed innate immune response that was associated with enhanced viral titres. In the chronic model, TGFB was over-expressed for 8 weeks, which resulted in thickening of the respiratory bronchiole epithelium and surrounding smooth muscle, and an emphysematous appearance within the airspaces, resembling phenotypic changes characteristic of asthma and COPD. Preliminary results in this model demonstrate that IAV infection is more severe compared to mice with normal TGFB levels.

Conclusion: Our transgenic mouse model provides us with a unique tool to evaluate the direct effects of TGFB on viral infection, or in the context of chronic inflammatory lung disease, and to investigate potential therapeutic strategies to combat viral-induced disease exacerbation. Aim: The primary source of airflow limitation in COPD is small airway (SA) fibrosis and obliteration. We previously showed that epithelial mesenchymal transition (EMT) is an active process in small airways contributing to fibrotic pathogenesis. Myofibroblast is highly active fibrotic cells that excessively secrete extracellular matrix (ECM). Here we explore the consequence of SA myofibroblast proliferation and relate them to physiological outcomes and airway remodeling in smokers and COPD patients.

Methods: SA lung resections, from non-smoker controls (NC), normal lung function smokers (NLFS), COPD current (CS) and ex-smokers (ES) were stained with anti-human αSMA, collagen-1, and fibronectin. αSMA+ cells were enumerated in Reticular basement membrane (Rbm),

Lamina Propria (LP), and adventitia and represented as per mm of Rbm and mm 2 of the respective area surveyed. Collagen-1 and fibronectin are represented as a percentage change. All measurements including the sub-epithelial LP and adventitia thickness were measured using Imageproplus 7.0.

We observed a general increase in sub-epithelial LP and adventitia thickness in all pathological groups compared to NC. Similar increases in αSMA+ myofibroblasts was observed in sub-epithelial Rbm, LP, and adventitia in the pathological groups compared to NCs, though the changes were prominently higher in the LP. Further, the increase in myofibroblast population in the LP was strongly associated with a decrease in lung function, and an increase in ECM proteins collagen-1 and fibronectin deposition in the LP. Finally, we observed EMT markers expressed in epithelial basal cells and Rbm, correlated to the increased SA myofibroblasts and airway thickness.

Conclusion: This is the first report that systematically characterizes the myofibroblasts in COPD based on their localization and statistically correlates them to lung function. The increase in myofibroblast population also directly related to pathological changes in ECM proteins. Driving these changes is likely to be EMT activity in the basal epithelial cells. Introduction/Aim: Skeletal muscle wasting is a major comorbidity of COPD and a powerful predictor of mortality. Current therapeutic strategies aim to increase muscle mass by augmenting protein synthesis and reducing protein degradation. Muscle mass can also be increased through the activation of satellite cells, which play a pivotal role in skeletal muscle regeneration. However, the role of satellite cells in COPD is not fully understood. Thus, we explored whether muscle regeneration in response to injuring the Tibialis Anterior (TA) muscle is impaired in mice exposed to cigarette smoke (CS).

Methods: Male BALB/c mice were exposed to room air (sham) or CS generated from 9 cigarettes/day, 5 days/week for 8 weeks. After 8 weeks of CS exposure, the right TA muscle was injured by injection of 40μl barium chloride (BaCl 2 ). The mice were then exposed to CS for another 7, 14 and 21 days at which time the contractile properties of the right TA muscle were measured. Mice were then culled and both the uninjured left TA and injured right TA muscles dissected out, weighed and used to examine the expression of genes associated with muscle regeneration (e.g. Pax 7) and for histological assessment of muscle injury.

Results: BaCl 2 -induced injury significantly decreased the weight of the TA muscle at 7 days post injury and this was further exacerbated in CS-exposed mice (n=10, p<0.05). BaCl 2 also caused significant muscle injury as demonstrated by centrally located nuclei and altered tissue architecture when assessed 7 days post injury. However, muscle injury was even greater in CS-exposed mice when compared to injured sham mice (n=8, p<0.05). Injured TA muscle from CS-exposed mice had at least a two-fold increase in Pax 7 mRNA expression compared to injured TA muscle from sham-exposed mice at 7 days post injury (n=8, p<0.001). Moreover, TA muscle contractile function was significantly impaired in the injured CS-exposed mice compared to the injured sham-exposed mice (n=7, p<0.05).

Conclusion: Skeletal muscle regeneration and function is impaired in experimental COPD. Introduction/Aim: Airway distensibility is reduced in patients with COPD. Transforming growth factor alpha (TGF-α) is increased in the serum of COPD patients and produces airway remodelling in mouse models. We hypothesised that TGF-α overexpression reduces airway distensibility. Our aim was to determine the effect of TGF-α and its regulatory gene, early growth response one (Egr-1), on airway thickness and distensibility.

Methods: Conditional expression of TGF-α in the airways of transgenic mice (Clara cell secretory protein-rtTA(+/-)/[tetO] 7 -TGF-α(+/-)) was induced by doxycycline (Dox). Mice were Egr-1 homozygous (+/+) or heterozygous (+/-). At 4 weeks of age, mice were fed Dox in chow or a control diet for 3 weeks and then anaesthetised, mechanically ventilated and had lung function measured using low frequency force oscillation. Airway conductance (G) was measured at trans-respiratory pressures of 0 (G 0 ) and 5cmH 2 O (G 5 ). Distensibility was calculated from the change in conductance (G 5 -G 0 ). Lungs were fixed for morphometry and stereology.

Results: Dox-fed mice had increased thickness of the airway epithelium, inner and outer wall and airway smooth muscle layer. While the increase in thickness of the epithelium and inner wall was greater in Egr-1 +/-mice, other changes were not affected by genotype. Dox-fed mice had reduced airway distensibility independent of genotype.

Conclusion: Increased TGF-α expression within the airway wall is associated with increased wall thickness and reduced airway distensibility. The effects of TGF-α were largely unaffected by partial modification of the Egr-1 gene. Findings suggest that TGF-α signalling may contribute to airflow limitation in COPD by reducing airway distensibility. Gold Coast Hospital and Health Services, Southport, Queensland, Australia, and 2 School of Medicine, Griffith University, Southport, Queensland, Australia Introduction/Aim: COPD patients with peripheral eosinophilia may have increased frequency of COPD exacerbations, respond better to oral corticosteroids and reduced mortality. Peripheral eosinophilia in COPD patients (eosinophil count of ≥ 2% of white blood cell count) has a prevalence in the range of 37-45%. To our knowledge, there is little epidemiological data of Australian COPD patients concerning peripheral eosinophilia, its prevalence and its association with rehospitalisation rates, steroid responsive disease and mortality rates. With this literature gap in mind, records of patients presenting with COPD exacerbations were audited retrospectively to determine the prevalence of peripheral eosinophilia in an Australian population.

Methods: Consecutive patients with spirometry confirmed COPD admitted to our institution with a COPD exacerbation during the period of July 2016 -December 2016 were considered for the study. These patients' records were subsequently followed up until June 2017. The variables recorded were white blood cell count, absolute and relative eosinophil count, readmission rate, decompensated type 2 respiratory failure rate, non-invasive ventilation initiation rate, intensive care admission rate and mortality rate.

Results: 240 patients were included for analysis and of these 37% had peripheral eosinophilia. Using Pearson's coefficient, there appeared to be a statistically significant correlation between increasing peripheral eosinophil count and increased number of readmissions (R=0.175, p=0.007) but not with decompensated type 2 respiratory failure, noninvasive ventilation initiation rate, intensive care admission rate or mortality rate. Two-sample t-Test for equal means when comparing those with peripheral eosinophilia ≥ 2% and those without was also in keeping with a statistically significant difference in readmission rates (t=-2.367, p=0.019).

patients was similar to overseas cohorts. In congruence with findings in previous overseas studies, Gold Coast patients with eosinophilia were prone to readmission but not increased type 2 respiratory failure, noninvasive ventilation, intensive care admission or mortality. As such peripheral eosinophilia can be used in Australian COPD patient cohorts to predict rehospitalisation rate. Future studies should look to prospectively evaluate the effect inhaled corticosteroids have on readmission rates in patients with peripheral eosinophilia.

Grant Support: None Introduction: Increased airway smooth muscle (ASM) mass is part of overall structural changes observed in COPD, and is correlated with severity of the disease and has been found to negatively impact lung function. Thus, there is clear unmet clinical need for finding new therapies for COPD which can target airway remodeling and disease progression. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed MAP3K activated by various stress stimuli, including ROS, TNF-α, and LPS. However, the role of ASK1 in airway remodeling is not established.

In this study, we aimed to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from wellestablished COPD patients.

patients have greater proliferative capacity to variety of mitogens in vitro.

We used human lung tissue samples and primary human ASM cells obtained from COPD patients and healthy controls. IHC revealed increased expression of ASK1 in COPD lung when compared with non-COPD lung. Pre-treatment of human ASM cells with highly selective (IC50:14 nM) and orally available ASK1 inhibitor; TCASK10 resulted in a dose-dependent reduction in mitogen (FBS, 10%; PDGF and EGF; 10 ng/ml, 72 hours)-induced ASM growth as measured by CyQuant assay. Furthermore, ASK1 siRNA prevented mitogen-induced human ASM cell growth, while immunoblotting revealed that the anti-mitogenic effect of ASK1 inhibition or silencing is mediated by JNK and p38MAP kinase-signalling pathways evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinase respectively with no effect on ERK1/2 signalling.

Conclusions: Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targeted to reduce or prevent excessive ASM mass in COPD. Introduction/Aim: Excessive pro-coagulant activity drives recurrent inflammation and fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF). Coagulation factors promote healing during damage, but can also exert pro-fibrotic cellular effects. Coagulation factor XII (FXII) has been identified as a potential mediator of lung fibrosis. The aim of this study is to further define a role for FXII in fibrogenesis.

Methods: Blood from 35 IPF patients was collected repeatedly (0-15 months) and compared to age and gender-matched healthy controls. Plasma FXII and IL-6 were measured. Immunohistochemical analysis for FXII was performed on paraffin-embedded lung tissue from IPF patients and non-diseased controls (NDC). In vitro effects of FXII on primary IPF and NDC fibroblasts were evaluated for cytokine production, proliferation and migration. The effect of a novel, fully human monoclonal antibody against FXII (CSL312) was evaluated.

Results: Baseline and longitudinal levels of FXII in IPF patients with progressive disease was elevated compared to those with stable disease (27.7 vs 17.6μg/ml, p=0.04 baseline; 26.3 vs 20.6μg/ml, p=0.014 longitudinal) but were not increased in IPF compared to healthy controls. Baseline plasma IL-6 was elevated in IPF patients when compared to healthy controls (3.9vs 1.5 pg/ml, p=0.001). IHC analysis revealed significant FXII staining in IPF lung tissue with minimal staining observed in non-fibrotic lung tissue. Activated FXII induced IL-6 production and enhanced proliferation/migration in primary lung fibroblasts. Migration and IL6 production were effectively inhibited by CSL312.

Conclusion: FXII is elevated in the lungs of progressing IPF patients and can drive pro-fibrotic and pro-inflammatory functions of fibroblasts. An anti-FXII antibody (CSL312) can inhibit these activities. The ability of FXII to drive IL-6 production in lung fibroblasts may contribute to elevated IL-6 levels seen in IPF patients' blood. Blocking FXII activity may be novel avenue to treat IPF and other inflammation-driven interstitial lung diseases. Introduction/Aim: Lung transplantation (LTX) provides a unique opportunity to investigate the dynamics of viruses present within the human pulmonary virome which is transplanted into the recipient within the donor lungs. The aim of our study was to elucidate interactions between viral species within the respiratory virome of the LTX recipient and describe their impact on allograft function.

Methods: A prospective, longitudinal study of viral dynamics after LTX. Multiple sample types were collected. Samples were processed and assayed using multiple uniplex PCRs for human rhinovirus (HRV), respiratory syncytial virus (RSV), influenza A and B, (Flu A, B), parainfluenza (PIV) 1,2,3 and human metapneumovirus. Clinical outcomes were analysed and compared with microbial detection.

Results: 52 consecutive LTX were recruited. Swabs of explanted lungs were positive for viruses in 18/52 despite recipient vaccination and negative recipient NPS. Day 1 BAL showed Flu A (n=28), HRV (n=9) and PIV (n=1). Donor swabs showed influenza (A=1, B=1), and HRV (n=3). Donor transmission of Flu A was observed. 47/52 recipients had BAL positive samples for viruses (38/47 on multiple BAL) and viruses persisted for up to 14 weeks.

114 paired transbronchial biopsies and viral PCR on BAL were performed. 21 patients showed evidence of acute cellular rejection on biopsy (Grade A2B0=3, Grade A1B1=6, Grade A1B0=12). Of these, 11/21 had viruses detected in the BAL collected concurrently. Conversely, in patients who showed no evidence of cellular rejection on biopsy, 51 were virus positive, while 42 were virus negative. Analysis using Fisher's exact test (2 tailed) indicated no significant correlation (p=1.00) between viral detection and the presence of acute cellular rejection.

The finding of frequent donor transmission and early acquisition of viruses (particularly influenza A) support the importance of respiratory virome surveillance after LTX to direct acute therapies. In this cohort, viral presence after LTX was not correlated with acute rejection events. Introduction/Aim: Previously we reported the therapeutic effect of BMPR2 augmented endothelial progenitor cell therapy in a rat PH model.

We know there is little direct cell integration into the pulmonary endothelium following intravenous injection, thus we attribute the positive physiological effects of our cell therapy to cell-to-cell communication via secreted factors such as exosomes (exos). In this study we look at comparing PAH-EPC and control-EPC protein profiles via mass spectrometry, and we assess their capacity to interact with and transport BMPR2 into endothelial cells (EC).

Methods: EPCs are isolated and cultured from 15mL of PAH or control peripheral blood. Cells were either transduced with AdBMPR2 or AdTrackLuc, or untransduced for subsequent exo isolations. Exosomes are isolated via differential centrifugation, and characterised with a Nano-Sight, TEM and SEM. Exosome protein profile was via mass spectrometry. Exo-Quick™ treated exos and GFP-exos labelled were used to view exo localisation within the target ECs both live and fixed via confocal microscopy. BMPR2-Exos were incubated on ECs for 48hrs before being washed off, and the cells lysed for western blot analysis.

Results: Exosomes were positively identified as 40-200nm via Nano-Sight, TEM and SEM. Protein profiling of exos showed differential protein expression in the PAH vs control for 326 proteins, including a relative down-regulation of BMPR2 in PAH exos. Exosome interaction with ECs demonstrated localisation around the nucleus of the cell, both in live and fixed EC samples. Additionally, BMPR2 expression was significantly increased in cells treated with BMPR2-Exos.

Conclusion: Differential protein expression between exos derived from PAH compared to control EPCs was shown. Additionally, we have characterised exos interaction with ECs and shown that they are involved in BMPR2 transfer from BMPR2 transduced EPCs to naïve ECs. These results indicate the potential role of exos in our BMPR2-cell therapy. Pharmacy. Alfred Health, Melbourne, Australia, 6 Cystic Fibrosis Service, Alfred Health, Melbourne, Australia, and 7 Lung Function Laboratory, Alfred Health, Melbourne, Australia Introduction/Aim: Lung transplant (LTx) recipients are at a high risk of lower respiratory tract infection (LRTI) secondary to immunosuppression, while altered respiratory physiology can make it difficult to clear secretions. Inhaled mucoactive agents alter mucus properties and/or facilitate mucocilliary clearance in suppurative lung disease. However there are no randomised controlled trials (RCTs) studying these effects post LTx. We aimed to evaluate the safety and efficacy of nebulised dornase alfa compared to isotonic saline during LRTI > 2 months post LTx.

Methods: Inpatient adults with LRTI and sputum production following bilateral sequential LTx were eligible for this assessor blinded RCT. Randomisation was stratified by LTx indication (AEcystic fibrosis (CF)). Participants received either 5ml isotonic saline, or 2.5ml dornase alfa, nebulised once daily for 1 month followed by 2 months symptom diary only. The primary outcome was change in lung clearance index (LCI) measured by multi-breath washout. Secondary outcomes included adverse events; spirometry; quality of life; readmission; length of stay and self-reported exacerbations at baseline, 1 month and 3 months.

Results: 32 participated, 16 each group (18M,14F), mean(SD) age 50AE14, FEV1% 58AE22, median(IQR) length of stay 7AE5, days since LTx 1275AE2482. LTx indications included CF (n=11) and chronic obstructive pulmonary disease (n=11). There were no significant between-group differences in LCI at any time point (one month mean difference -0.34, 95% confidence interval (CI) -1.57 to 0.89; three months mean difference -0.76, 95% CI -2.29 to 0.78, both favouring dornase alfa). Secondary outcomes were not different between groups.

Poor tolerability and large variation in efficacy of pirfenidone is a significant barrier to best patient outcomes. This study aims to investigate whether an in-vitro fibroblast test can identify patients most likely to benefit from pirfenidone therapy.

Methods: Primary lung fibroblasts were derived from the apex and base of the lungs from patients with IPF (N=10), patients with other endstage non-IPF ILDs (N=10) and normal donors whose lungs were deemed unsuitable for transplantation (NDC)(N=10). Determined by in-cell western, αSMA and GAPDH levels in fibroblasts were measured before and after treatment with pirfenidone (0-1mM) and in the presence/absence of transforming growth factor-β (TGFβ) (0-10ng/mL). Sensitivity to pirfenidone was defined by a decrease in αSMA/GAPDH level from baseline by ≥10%.

Results: Treatment with pirfenidone decreased αSMA levels in N=9 fibroblast lines at 72 hours ( Figure 1 ). Fibroblast αSMA levels correlated with the extent of αSMA decline in response to pirfenidone (Spearmans' R = -0.76, p=0.037). In patients with IPF, basal αSMA level of the fibroblast line correlated with forced vital capacity (FVC, % predicted) of the patient from whom the line was derived (Spearmans' R = 1, p=0.016).

The response of lung fibroblasts to pirfenidone may identify patients with IPF who would benefit from said treatment. Our data suggest that patients who have high numbers of αSMA+ fibroblasts would in particular benefit from pirfenidone therapy, although further screening is required. Variation in αSMA level of fibroblasts may be reflective of the overall lung fibrotic burden as it correlated with FVC.

Grant Support: None Methods: EPCs were isolated from PAH and control patient's peripheral blood (15mL). Following characterisation and expansion, cells were exposed to either normoxia (5%CO 2 / atmosO 2 ) or hypoxia (1%O 2 /5% CO 2 /94% N 2 ). Proliferation and apoptosis were assessed using MTT assays and flow cytometry. Protein analysis was conducted via western blots.

Results: EPCs originating from PAH patients proliferated at a similar rate to control EPCs in normoxia (increases of 198%AE60% and 206%AE

17% over 72hrs respectively). However, under hypoxic conditions proliferation of control cells was 88% less than PAH cells (7%AE36% and 95%AE 11% increase over 72hrs respectively). Preliminary data suggests this continued proliferation could be due to apoptosis resistance in PAH lines as assays revealed lower apoptosis levels after hypoxia exposure for 72hrs in PAH lines (2.8%) than in control lines (8.5%). Activated SMAD 1/5/8 was decreased by 68% in hypoxic PAH cells compared to controls.

Conclusion: EPCs isolated from peripheral blood of PAH patients are functionally different under hypoxic conditions to those isolated from control subjects. Most notably, the PAH EPCs appear to possess a higher resistance to apoptosis and hypoxia. These findings suggest EPCs could play a role in the pathogenesis of PAH as they can contribute to the aberrant proliferation, apoptosis and vascular remodelling seen in PAH. Grant Support: NHMRC, RAH Research Fund. to an exacerbation of COPD is associated with poor clinical outcomes and increased mortality. Non-invasive ventilation (NIV) is part of the standard of care but can be poorly tolerated.

We have shown Nasal High Flow therapy (NHF) produces a small reduction in transcutaneous CO 2 tension (PtCO 2 ) in stable COPD.

Our aim was to compare NHF and NIV in hypercapnic COPD.

Methods: Design: Single-blind randomised controlled two-way crossover trial.

Setting: Single centre institute in New Zealand recruiting participants from hospital databases.

Participants: 24 participants with a doctor's diagnosis of COPD, FEV 1 :

FVC ratio <0.7, ≥40 years, smoking history of ≥10 pack years, PcapCO 2 >45.0mmHg, BMI <35kg/m 2 , no recent exacerbations and no diagnosis of obstructive sleep apnea or obesity hypoventilation syndrome.

Interventions: NHF at 45Lmin and BiPAP at 15/4cmH 2 O, each for 60mins with a 15min washout in between.

Primary outcome measure: PtCO 2 at 60mins, adjusted for baseline. Secondary outcomes included tolerability and the proportion of participants with a decrease in PtCO2 ≥4mmHg and ≥8mmHg at 60 minutes.

Results: PtCO 2 was 2.5mmHg (95% CI -4.5 to -0.5) lower with NIV compared to NHF, p=0.016.

The proportion of participants with a reduction of PtCO 2 ≥4mmHg with NIV versus NHF was 45.8% versus 25.0%. For a reduction in PtCO 2 ≥8mmHg it was 25% versus 8.3%. These differences were not statistically significant. Participants rated NHF significantly better for ease of application, comfort, fit and willingness to use in the future.

In stable COPD patients with chronic hypercapnia, NIV resulted in a small reduction in PtCO 2 compared with NHF, which is of uncertain clinical significance. NHF was better tolerated. NHF may be a therapeutic option for some people with hypercapnic respiratory failure and studies in acute exacerbations of COPD are required. Methods: Nasopharyngeal viral PCR, sputum culture, C-reactive protein, chest X-ray, troponin I (hs-TnI), N-terminal pro brain natriuretic peptide (NT-proBNP) and Hospital Anxiety and Depression Scale (HADS) were used to construct a cumulative aetiological phenotype for each AECOPD using a simple acronym: A=airway viral infection, B=bacterial infection, C=coinfection, D=depression/anxiety, E=embolism (pulmonary), F=failure (cardiac), G=general environment, X=unknown.

Results: Aetiologies identified among 155 unique AECOPD admissions were diverse (viral=35, bacterial=61, coinfection=8, no infection=44) and often multifactorial, with 1 aetiology in 31%, 2 in 48.4%, 3 in 5.2% and no identifiable aetiology in 5.8%. Baseline lung function and symptoms were similar across exacerbation subtypes. Infective exacerbations were associated with lower eosinophils (p<0.001) and non-infective exacerbations with lower pH (p=0.004). NIV requirement was higher in non-bacterial v bacterial (p=0.03). AECOPD patients with no identifiable aetiology (X) were generally "frequent exacerbators" with severe acute presentations but prompt stabilization. Admissions ≤4 days were most common in non-infective groups (viral 22.9% v bacterial 39.3% v co-infection 12.5% v non-infective 47.7%, p=0.06). Subclinical cardiac dysfunction was highly prevalent in both infective and noninfective AECOPD with elevated hs-TnI in 27.3% and elevated NT-proBNP in 61.7% overall. Anxiety/depression was prevalent in all aetiological subgroups (overall population HADS mean/SD =16.7/8.7). Survival at 12 months post discharge was lower in non-viral versus viral AECOPD (p=0.03).

Conclusion: Hospitalized AECOPD are multidimensional and multifactorial. Subtyping by infection type identified significant differences in comorbidities, health care utilization, laboratory parameters, inpatient management and post exacerbation survival. Anxiety/depression and cardiac dysfunction appear prevalent but underdiagnosed. Our clinically oriented methodology provides a feasible framework for clinicians and researchers to address AECOPD complexity and target therapeutic interventions.

Grant Support: This project was supported by an unrestricted educational grant from GlaxoSmithKline.

Editorial material and organization © 2018 Asian Pacific Society of Respirology. Copyright of individual abstracts remains with the authors. Introduction: Treatment with β-adrenoceptor agonists may not overcome symptoms of severe asthma. Relaxin (rhRLX), an RXFP1 receptor agonist, exerts cardioprotective effects in acute heart failure and elicits vascular relaxation via RXFP1 and nitric oxide signalling. Although we have previously established its bronchodilator efficacy in rat airways (Lam et al., 2016) , its effects in other species and its potential to enhance β-adrenoceptor-mediated relaxation have yet to be explored.

Aim: To compare the bronchodilator effects of relaxin alone and in combination with the β 2 -adrenoceptor agonists, isoprenaline (ISO) or salbutamol (SAL) in multiple species.

Methods: Tracheal rings or bronchi were dissected and/or precision cut lung slices (PCLS) containing intrapulmonary airways were prepared from mice, rats, guinea pigs and marmosets and human lungs (unused donor). rhRLX alone and in combination with ISO or SAL were added to airways pre-contracted to MCh.

Results: rhRLX (100 nM) elicited partial relaxation in rat airways that was more rapid in PCLS than trachea but was ineffective as a direct bronchodilator in guinea pig trachea or mouse PCLS. rhRLX markedly increased the potency of ISO by 10-fold in rat PCLS without increasing maximum relaxation, and of SAL by 27-fold in guinea pig trachea. SAL only elicited partial relaxation in mouse PCLS but synergism was evident between rhRLX and SAL (maximum relaxation: rhRLX no response; SAL 41AE5%; rhRLX/SAL 90AE6%; n= 4-7; P<0.001). Preliminary data showed rhRLX elicited relaxation and potentiated SAL-mediated relaxation in marmoset and human small airways.

Conclusion: rhRLX elicits airway relaxation in some species and enhances responsiveness of both small and large airways to salbutamol across all species tested. Since rhRLX increases the potency of salbutamol, further investigations are warranted to define its therapeutic potential as an add-on asthma therapy in human lungs, particularly when responsiveness to current dilator therapy is limited. (1). The aim was to determine the effect of Cgp91 treatment on the lung pathology induced by a highly pathogenic strain of IAV.

Methods: Male C57Bl/6J mice were treated daily via intranasal administration with Cgp91 (0.2mg/kg) or DMSO (2%; control) over a 4day period. Mice were infected with the PR8 (H1N1; 500 PFUs) strain of IAV or PBS control, one-day post initial drug treatment and analysed at day 3 post-infection. Bronchoalveolar lavage (BAL) fluid collected from mice was used to assess airway inflammation. Histopathological analysis of lung was assessed using H&E stain and scored for alveolitis, inflammatory cell infiltrate and peribronchiolar inflammation. Superoxide generation in the BAL was measured using L-012 enhanced chemiluminescence and changes in cytokine and viral mRNA expression in the lung were quantified using real-time QPCR.

Results: Cgp91 treatment significantly (P<0.05) reduced airway inflammation, neutrophil influx, and pulmonary inflammation as measured by the degree of alveolitis, inflammatory cell infiltrate and peribronchiolar inflammation. Additionally, Cgp91 attenuated ROS generation and influenza viral mRNA expression in PR8-infected mice.

The spatial inhibition of NOX2 in endosomal compartments with Cgp91 could be used as a potential treatment strategy for highly pathogenic influenza A virus infections.

Grant Support: NHMRC Australia (Project Grant ID 1122506,

Introduction: Based on limited available data, amoxycillinclavulanate is the current recommended first-line empirical oral-antibiotic treatment for non-severe bronchiectasis exacerbations in children. Azithromycin is an attractive alternative because of its long half-life, reduced dosing schedule, and good safety profile in children. We tested our primary hypothesis that oral azithromycin is non-inferior (within 20% margin) to amoxycillin-clavulanate at achieving resolution of exacerbation by day-21 of treatment in children with bronchiectasis.

Methods: We conducted a multicentre, parallel group, doubledummy, double-blind placebo-controlled RCT trial in 4 centres. At the start of an exacerbation, 179 children were randomised to receive either amoxycillin-clavulanate (22.5 mg/kg bd)/placebo or azithromycin (5mg/kg/ day)/placebo for 21-days. Our primary outcome was resolution of exacerbation (defined as 'return to baseline') by 21-days. Study was powered for 90% (α=0.05, 1-sided) with 20% non-inferiority margin to detect 80% resolution rate by day-21. Secondary outcomes were cough-specific quality of life (PC-QoL) and duration of exacerbation. Generalised linear model was used to calculate relative differences between groups.

Results: Baseline characteristics of the 2 groups (amoxycillinclavulanate n=97 and azithromycin n=82) were similar. By day-21, resolution was comparable between groups, relative risk 0.99 95%CI 0.84-1.17, falling within the a-priori calculated 20% non-inferiority margin. Between group differences for duration of exacerbation (2 days 95%CI -1.7, 5.3) and PC-QoL at day-21 compared to beginning of exacerbation was also within our non-inferiority margin (0.42, 95%CI -0.06, 0.89).

Conclusion: Azithromycin is non-inferior to amoxicillin-clavulanate for treating non-severe exacerbations of bronchiectasis in children. Azithromycin may be preferred to amoxicillin-clavulanate in selected settings e.g. adherence. However, its use needs to be balanced with risk of treatment failure (within 20% compared to amoxicillin-clavulanate) and inducing macrolide resistance. Faculty of Sciences, University of Technology Sydney, Broadway, Australia Introduction/Aim: Persistent airflow limitation (PAL) may develop in older non-smokers with asthma however the mechanism is unknown. Reduced lung elastic recoil may contribute as this occurs with age and may occur in asthma. Neutrophilic airway inflammation is also more common in older people with asthma. We aimed to determine the relationship between lung elastic recoil, airway inflammation and airflow limitation. We hypothesise that reduced lung elastic recoil and neutrophilic airway inflammation are associated with PAL in older non-smoking asthmatics.

Methods: Non-smoking adults with asthma, treated with standardised high dose inhaled corticosteroid/long acting beta agonist for two months, underwent standard lung function, lung elastic recoil measurement using an oesophageal balloon to derive indices of loss of lung elastic recoil (increased K and reduced B/A), and bronchoscopy to obtain bronchoalveolar lavage fluid (BAL) for differential leukocyte count and T H 17 cytokine measurement. Spearman correlations were assessed and multiple linear regressions were used to adjust for age, BMI and disease duration.

Results: Nineteen subjects (11 male; meanAESD age 63AE9 years, asthma duration 38AE22 years) demonstrated moderate PAL ((meanAESD z-score) post-bronchodilator FEV 1 -2.05AE0.75, FVC -0.61AE0.95, FEV 1 / FVC -2.46AE0.90). Reduced lung elastic recoil was demonstrated in 8/18 subjects (median (IQR) z-score K 1.57(-1.08-3.43), B/A -1.18(-1.65--0.02)). FEV 1 /FVC correlated negatively with K (r=-0.53, p=0.023) independent of age, BMI and disease duration. Neutrophilic airway inflammation was not demonstrated (meanAESD: neutrophils 9.1AE18.1%, n=10). Lung elastic recoil did not correlate with BAL neutrophil count or T H 17 cytokines.

Conclusion: Loss of lung elastic recoil contributes to PAL in older non-smokers with asthma. This may be due to lung tissue changes in addition to airway remodeling. Despite the lack of relationship with airway inflammation in this exploratory study, the underlying cellular mechanisms require further investigation. An alternate paradigm of 'lung remodeling' would have potential implications on preventing PAL in this population.

Editorial material and organization © 2018 Asian Pacific Society of Respirology. Copyright of individual abstracts remains with the authors.

Methods: Primary human airway smooth muscle cells were stimulated with increasing concentrations of 18mg/ml nicotine and 0mg/ml nicotine (tobacco and menthol flavoured, Vaper empire) E-vapour extract for 24 hours. An MTT assay was performed to determine cytotoxicity and ELISA was used to assess IL-6 and CXCL8 production. Cells were isolated from explanted and resected lung tissue from COPD patients and smokers without COPD.

Results: All 4 E-vapour extracts were cytotoxic to cells (n=9-14, p≤0.0001), cytotoxicity of E-vapour was increased in aerosols created at higher temperatures. All 4 E-vapour extracts stimulated CXCL8 production compared to unstimulated controls (n=14, p<0.05). Cells from people with COPD were hyperresponsive to E-vapours, with 18mg/ml nicotine tobacco flavoured E-vapour stimulating significantly greater CXCL8 production from COPD cells compared to non-COPD cells (n=7, p<0.05). IL-6 production was not stimulated.

Conclusion: E-cigarettes have the potential to contribute to the pathology of COPD. Cytotoxicity can cause cell death and ineffective repair, as seen in both the airways and parenchyma in COPD. Increased CXCL8 would contribute to the proinflammatory environment in the lung. Our data suggests that COPD patients should not use them as a smoking cessation aid or cigarette replacement. Introduction/Aim: Many preschoolers with asthma experience disease remission. As the first 5 years of life may offer a window of opportunity to modify long-term outcomes, we explored the relationship between the likelihood of remission and asthma control in the two years following the diagnostic of asthma in preschoolers.

Methods: We assembled a retrospective birth cohort of children born between 1990-2013 in four Canadian provinces (Quebec, Manitoba, Saskatchewan, British Columbia). Preschool asthma was defined by one hospitalisation or 2 medical visits within a 2-year period for asthma in children aged less than 5 years. Remission was assumed after two years without any asthma-related drug claims, medical visit or hospitalization. The main exposure was asthma control in the 2 years following diagnosis, measured on the validated 4-level Pediatric Pharmacoepidemiology Asthma Control Index (PPACI) and ascertained over 4 consecutive 6-month periods. Cohort exit occurred at death, loss of medical or drug coverage, or date of last available data. Within each province, a Cox regression model served to estimate the strength of association between the PPACI stability over 2 years post diagnosis and remission, after adjusting for potential confounders and covariates, namely demographics (e.g., sex, social assistance), disease characteristics (e.g., age, atopy), therapy (e.g., first controller therapy). A random-effects meta-analysis aggregated the province-specific results.

Results: Of 1.3 million live births in the 4 provinces, 118,785 children less than 5 years met the definition of asthma; 63% were male, 69% were aged less than 3 years at diagnosis. The pooled rate of remission was 7.74 (95% CI: 7.67, 7.81)/100 person-years. Poorer asthma control over the 2 years following diagnosis was associated with incrementally lower likelihood of asthma remission (Table) . Methods: Hourly PM 2.5 from the fire at 1x1 km 2 was derived from an atmospheric transport model. Daily average and maximum PM 2.5 were assigned to participants' residential address during the fire. Lung function was evaluated using the forced oscillation technique (FOT), which generated z scores for resistance (Rrs) and two measures of reactance as follows: (1) Reactance at a frequency of 5Hz, (Xrs) and (2) area under the reactance curve (AX). We used generalised linear models, adjusted for maternal smoking in pregnancy and maternal stress during the fire to assess associations between PM 2.5 exposure and lung function. Conclusion: This is the first report to describe CT lung findings after CFTR corrector/potentiator therapy in patients 6-11 years of age homozygous for F508del. In this 24-week exploratory analysis, bronchiectasis and air trapping scores improved in patients treated with LUM/IVA and worsened in the placebo group. These data suggest that LUM/IVA may reduce CF disease-related changes in lung morphology and support the need for further study. Introduction: Low attenuation regions (LAR) on chest CT are an important component of end-stage lung disease and reflect small airways disease in cystic fibrosis (CF). However, the extent of LAR reversibility in young children is unknown. We aimed to assess localised changes in LAR distribution over time in relation to CF-lung disease outcomes. We hypothesised that a proportion of LAR is irreversible in young children with CF and indicative of clinical severity.

Methods: Children in the AREST CF cohort contributed CT scans and clinical data from annual consecutive visits. Localised changes in LAR distribution were assessed using specialised image analysis software by matching CT lung images from two time points and measuring the lung volume proportion of new (%LARnew), reversed (%LARreversed) and stable (%LARstable) LAR. Linear mixed effects models adjusted for age and multiple visits, assessed differences between LAR outcomes and their association with clinical predictors. These include: age, pancreatic sufficiency, bronchiectasis extent determined from the PRAGMA-CF method and pulmonary inflammation and infection measured by bronchoalveolar lavage. Introduction/Aim: Studies show that a significant proportion of infants with cystic fibrosis (CF) have diminished lung function within the first 2 years of life. However, it is unknown whether lung function tests in infancy have the potential to predict worse prognosis and determine which infants are most likely to benefit from treatment early in life. This study aims to investigate whether diminished lung function detected in infants diagnosed following newborn screening is associated with worse lung function when re-measured at school-age.

Methods: Lung function was assessed in 58 individuals with CF diagnosed after newborn screening (0-2 years) and again at school age (7-10 years). The raised volume rapid thoraco-abdominal compression (RVRTC) technique and multiple breath washout (MBW) test was performed at infancy, and spirometry and MBW performed again at schoolage. Mixed-effects models were used to determine if outcomes from RVRTC such as forced expiratory volume in 0.5 second (FEV 0.5 ) and FVC, as well as lung clearance index (LCI) from the MBW test were associated with FEV 1 , FVC and FEV 1 /FVC measured by spirometry, and LCI at school-age.

Results: Age and height-adjusted FEV 0.5 and FVC and heightadjusted LCI at infancy were not associated with zFEV 1 , zFVC and zFEV 1 /FVC and LCI at school-age. The coefficients, 95% confidence intervals and p-values of the mixed-effects models are shown below. Methods: Asymptomatic CF adults were recruited from the outpatient CF clinic. In a quiet room, PTA examined frequencies of 500Hz to 6000Hz, whilst HFA tested frequencies of 8000Hz to 16000Hz. Hearing loss severity was categorised as follows: 26-40dB (slight), 41-60dB (moderate), 61-80dB (severe), and 81+dB (profound), recording the worst 2 consecutive frequencies in standard and high ranges.

Results: A total of 134 CF adults, mean (SD) age 26.7 (8.7) years were recruited. Standard PTA detected hearing loss in both ears with 5 showing slight, 3 moderate and 2 severe impairment. HFA detected more hearing loss with 20 having slight, 16 moderate, 9 severe and 4 profound impairment. All those with hearing loss at standard frequencies exhibited similar or worse abnormalities at high frequencies. Older patients showed more hearing abnormalities both at standard and high frequencies.

Conclusion: These preliminary results suggest that HFA is more sensitive than standard PTA for measurement of potential hearing loss in the CF population. Comparison of these results with the cumulative doses of aminoglycosides is being undertaken in this cross-sectional study.

Grant Support: This study was supported by a Novartis Grant-in-Aid. Methods: Information was obtained through computer records and included basic patient demographics, prior history of haemoptysis or venous thrombosis, complications and outcomes.

Results: A total of 121 4Fr PICC insertions in 63 patients (33 males and 30 females) took place during the study period. Twenty-eight percent of patients had a history of haemoptysis and one fifth (13/63; 20.6%) had a prior history of DVT or pulmonary embolus. The majority of patients had PICC lines inserted by a Radiologist (55.4%) and the rest were performed by Nurse Practitioners (44.6%). Symptomatic DVT (or pulmonary embolism) occurred in 6/121 (4.96%).

Conclusion: Our audit shows that the rate of PICC-associated DVT in adults attending the WA adult CF centre is equivocal to that reported in the literature of between 3.5 -16.4%. It is well recognised that factors including PICC size, the thrombotic state of patients with CF and history of DVT can impact the likelihood of PICC-associated DVT. Following this audit we plan to assess the role of enoxaparin prophylaxis, particularly in the outpatient setting, aiming to further minimise the risk of PICC associated DVT.

Introduction/Aim: Pleural fluid pH and glucose levels are both recommended in current guidelines as investigations in the workup of pleural effusions. Both parameters are reduced in inflammatory and/or metabolically active conditions. Whether pleural fluid pH and glucose levels provide duplicated information or independent knowledge is unclear. We aimed to investigate the relationships between pleural fluid pH and glucose levels in unselected pleural effusions, and the incidences of discordance in their levels.

Methods: Setting: Pleural services of three centres in Spain, UK and Australia.

Data: Clinical information and pleural fluid pH and glucose levels were collected.

Analyses: i) To assess the relationship between pH and glucose using smooth curves from restricted cubic spline models; ii) Concordance between pH and glucose for varying cut-off levels was assessed.

Results: Pleural fluid samples (n=2971) were separated into four categories: malignant (n=1045), bacterial infection (n=1133), TB pleuritis (n=544) and other benign effusions (n=249). The mean pH was 7.38 (SD 0.22) and median glucose was 5.99 (range 0-29.4) mmol/L. Linear regression modelling of the relationship between glucose (log-transformed) and pH with a restricted cubic spline showed linear (p<0.01) and nonlinear effects (p<0.01). Most (91.6%; n=2720) of the samples were concordant in pH and glucose levels (i.e. at cutoffs of 7.20 and 3.3mmol/L respectively). Concordance was the lowest in the TB group (80.7%) and highest in the other benign pleuritis group (98.2%). Patients with a low pH but high glucose (n=99) were more likely to be diabetic (31% were diabetic vs 8% of those with low glucose and high pH), p<0.001, and have bacterial infection. Introduction/Aim: Indwelling pleural catheter (IPC) is an effective treatment for recurrent, especially malignant, pleural effusions. Pleural infection, though uncommon, remains physicians' major concern in the use of IPCs. Intrapleural tPA/DNase therapy has revolutionized care of pleural infection, but its use in IPC-related pleural infection has not been the subject of prior reports.

Methods: Single centre, retrospective review of patients with IPCrelated pleural infection treated with tPA/DNase in our tertiary pleural unit. Demographics, interventions and outcomes of treatment were described. Introduction/Aim: Bronchoscopic lung volume reduction (BLVR) via endobronchial valve (EBV) insertion is an accepted treatment for patients with severe emphysema. The most common complication of EBV insertion is pneumothorax, with a reported incidence of up to 25%. The aim of this study was to determine if previous pleural injury, or paraseptal/panlobular emphysema morphological subtype, would contribute to pneumothorax risk post-EBV insertion.

Australia over the period 2014 to September 2017 were examined in 3 centres: the Royal Adelaide Hospital, The Queen Elizabeth Hospital, and ChestCare Clinic. Emphysema subtype was determined by evaluating pre-EBV CT chest scans. The presence of pleural injury was determined by assessing patients for previous pneumothorax, pleural instrumentation, and pleural plaques/nodules in their pre-EBV CT chest scans.

Results: 86 procedures were completed within the study timeframe.

13 (15.1%) procedures resulted in pneumothorax. Mean age at EBV insertion was 67.31 years. 54.6% (47/86) of EBV insertions occurred in male patients. Statistical analysis was undertaken via logistic regression.

Previous pleural injury significantly increased the risk of pneumothorax post-EBVI (OR 22.55, 95% confidence interval 2.51-202.51, p = 0.005,). Gender, age at EBV insertion, and paraseptal/panlobular emphysema subtypes did not significantly increase pneumothorax risk.

Conclusion: This is the first Australian study to examine risk factors for pneumothorax incidence in EBV insertion. Previous pleural injury significantly increases the pneumothorax risk after EBV insertion. This data will contribute to our ability to predict pneumothorax in patients evaluated for EBV insertion, thus allowing improved risk assessment, and facilitating discharge planning post-EBV insertion. We plan further studies evaluating other possible risk factors, including quantitative CT scoring of pleural adhesions.

Grant Support: None Introduction/Aim: Obstructive sleep apnoea (OSA) is common and associated with significant morbidity and mortality. There are few objective prevalence data in Australia, particularly for women. In Busselton, Western Australia, the prevalence of OSA (respiratory disturbance index >15) was estimated in 1990 at 4.7% in men, and in 2007 (N=793) at 12.4% in men and 5.7% in women (apnea-hypopnea index (AHI)>15 in participants without known OSA). We assessed OSA prevalence in the Busselton Healthy Ageing Study, a comprehensive health study of both sexes aged 46-64 years.

Shire electoral roll born 1946 to 1964 were invited to participate, with 75% participance (N=5,082). Dual channel ApneaLink devices for home sleep study were issued to 3,745 participants (73.7%) and 2,707 (53.3%) collections were suitable for analysis. The prevalence of OSA was defined by the AHI obtained from the ApneaLink automated event scoring algorithm, and its relation to demographic data and co-morbidities was assessed. Moderate and severe OSA were defined as AHI>15 and >30 respectively.

Results: The prevalence of OSA (AHI>15) 20.4% in men and 10.1% in women (see table) . Increasing OSA severity was associated with increased BMI and alcohol use in both sexes, and with sleepiness in men only.

The prevalence of OSA in Busselton has increased, and the prevalence in women is higher than previously reported. Sexbased differences in comorbidities are observed. to breathing is determined via the presence of a Bereitschafts (readiness) potentiala low amplitude negativity which begins~1s before inspiration. In chronic obstructive pulmonary disease (COPD), changes in the lung, chest wall and respiratory muscles induce an inspiratory load. We hypothesised that there is a cortical contribution to quiet breathing in COPD and that a cortical contribution to inspiratory threshold loading is related to dyspnoeaa major symptom of COPD.

Methods: Electroencephalographic activity (EEG) was recorded in 15 COPD patients (10 males; age: 57-87) and 30 healthy controls (15 age-matched and 15 young) during quiet breathing and inspiratory threshold loading (10% maximal inspiratory pressure). Two blinded observers evaluated the presence of Bereitschaftspotentials prior to inspiration from ensemble averages of 80 or more epochs of EEG at Cz and FCz. Dyspnoea was rated using a modified Borg scale.

Results: The incidence of a cortical contribution to quiet breathing was significantly greater in the COPD patients (7/15) than the young (0/15) (P < 0.01), but not the age-matched (5/15) (P = 0.46), controls. A cortical contribution to inspiratory threshold loading was associated with higher Borg scores in the young (P < 0.05), but not the age-matched controls (P = 0.25) or the COPD patients (P = 0.43).

Conclusion: This study provides evidence that age, rather than COPD, is associated with a cortical contribution to quiet breathing. A cortical contribution to inspiratory threshold loading may be associated with more severe dyspnoea, at least in healthy young people. Positive Airway Pressure (CPAP) in the treatment of Obstructive Sleep Apnea (OSA) and well validated benefits in quality of life and health outcomes, long term adherence remains a major challenge. Remote access cloud based technology has become a standard feature of new CPAP devices. Currently, this feature may not be optimally utilised to improve compliance and patients' experience with CPAP.

We sought to determine whether, remote based assessment of CPAP usage at regular intervals with follow up telephone assessment could improve CPAP usage and Epworth sleepiness score (ESS) in patients commencing CPAP therapy for OSA through a well-supported sleep service.

Methods: We sought to prospectively assess 50 consecutive patients commencing CPAP therapy for OSA. Each patient had CPAP usage remotely assessed at weeks 1, 3, 6 and 9 post commencement. Telephone assessment with a standardised questionnaire was carried out at each interval if CPAP usage was <4/hrs per night. CPAP usage and final ESS were compared to 50 consecutive retrospective controls. Current preliminary data includes 37 of target 50 patients in the intervention group. Introduction/Aim: Mechanical ventilation, a lifesaving therapy for patients with respiratory failure, contributes to mortality by inducing inflammation, which can lead to multisystem organ failure. Different regions of the lung have been shown to heterogeneously respond to mechanical ventilation, however, the association between this variation in regional lung distension and regional lung inflammation is unknown. The aim of this study was to assess this association in the healthy lung.

We ventilated two groups of adult BALB/c mice (n = 8 per group) for 2 h using a protective [low tidal volume with moderate positive end expiratory pressure (PEEP)] or injurious [high tidal volume with zero PEEP] ventilation strategy. RNA levels of 19 genes were quantified regionally by qPCR array. Gene expression was correlated with regional FRC, tidal volume and distension (FRC + tidal volume). FRC and tidal volume were obtained from analysis (cross-correlation-based velocimetry) of dynamic high-resolution (phase contrast) 4DCT lung images at baseline and after two hours of ventilation.

Results: Two genes had differential regional expression that varied between ventilation strategies (IL-6, P=0.02 and Ccl-2, P<0.01). The expression of these genes was positively correlated with regional tidal volume and distension (P<0.05 for all correlations). The expression of Cxcl2, Tnf-α, Wnt1, c-fos and Nfe2l2 also varied between ventilation strategies (P<0.01), but they did not appear to be associated with FRC, tidal volume or distension.

We have demonstrated associations between regional gene expression and tidal volume. Our results provide critical insight into the regional lung response to mechanical ventilation. In particular, these results highlight the importance of the balance between under-ventilation and over-stretch (tidal volume) and how each of these can contribute to lung inflammation and, potentially, patient outcomes. Introduction/Aim: Although significant progress has been made in asthma management, 5-10% of patients have severe asthma (SA) that is associated with increased morbidity, mortality and an economic burden. Within this group, 30-40% of patients are prescribed continuous or nearcontinuous oral corticosteroids (OCS) to achieve or maintain asthma control. However, in primary care, a subset of these patients may exist with poor asthma management practices and thus less severe disease, relying on OCS to achieve asthma control instead of regular inhaled preventer medication. The aim of this study is to identify patterns of medication taking behaviour and describe the respiratory status of people with asthma in primary care. This will allow for the development of a framework that identifies patients based on asthma severity through medication records.

Methods: Patient data (n=493) was utilised from a quality-controlled community pharmacy database. Correlational analysis and regression modelling were employed to determine potential predictors of asthmatic oral corticosteroid users (n=72) based on asthma severity, lung function, symptom control, comorbidities, adherence, inhaler technique and medication management.

Results: Fifteen percent of asthmatics recruited were prescribed OCS in the last 12 months. Ninety-three percent of OCS users were classified as having poor asthma control, 96% identified potential barriers to non-adherence (determined by the Brief Medication Questionnaire (Svarstad BL et al. 1999 )), and 86% had incorrect inhaler technique. Significant relationships were found between OCS users and ownership of an asthma action plan (p<0.00), the existence of depression (p=0.002) and eczema (p=0.02), potential for non-adherence (p=0.018), poor asthma control (p<0.00), poor lung function test (p=0.04) and a higher prescribed rate of inhaled combination therapy (p<0.000), including a higher rate of visits to the doctor regarding asthma (p=0.044).

Conclusion: This research has uncovered a heterogeneous group of people with asthma in primary care, with less severe disease who put themselves at risk of exacerbations due to their medication taking behaviour. By better understanding the behaviour of individuals in the context of their day-to-day management, we will be able to tailor interventions for these patients reflecting current guidelines. more likely to report presenteeism (95%CI 1.75-5.69) and 2.26 times more likely to report daily activity impairment (95%CI 1.44-5.54). Having poorer asthma control or more exacerbations in the previous year was associated with greater absenteeism, presenteeism and activity impairment (all p<0.05). Worsening asthma control scores were associated with increasing presenteeism over time (time interaction p=0.011). In participants with severe asthma, worse asthma control (p<0.001), asthmarelated quality of life (p<0.001), depression symptoms (p=0.001) and anxiety symptoms (p=0.002) were associated with greater odds of presenteeism.

Conclusion: Impaired work and non-work functioning are important components of the disease burden of severe asthma. Optimising workplace productivity requires improvement in asthma control and attention to mental health. Absenteeism and presenteeism may be key metrics for assessing intervention efficacy among people with severe asthma of working age. Grant Support: SAWD is supported by GSK, Roche, AZ, Novartis and Boehringer Ingelheim. Introduction/Aim: Glucocorticoids (GCs) remain central to treatment of asthma, but therapeutic responses are impaired in severe asthma and during asthma exacerbation. Our laboratory found TGF-β1 per se impairs GC activity, and is a key mediator of viral infection-induced GC insensitivity in airway epithelium. The key CLOCK component CK1δ/ε, implicated in TGF-β1 signalling, also regulates GCs activity. In the current study, we demonstrate that targeting CK1δ/ε prevents TGF-β1-indcued GC insensitivity, and attenuates virus mimic Poly (I:C)-induced inflammatory responses.

Methods: Differential expression of CK1δ/ε was assessed by IHC in human asthmatic cohort. GC responsiveness of bronchial epithelial cells (BEAS-2B, air-liquid interface (ALI)-differentiated primary human bronchial epithelial cells (HBEC)) in the presence of TGF-β1 was assessed by RT-qPCR and GRE-SEAP. Poly (I:C)/TNF-α-induced inflammatory responses in BEAS-2B cells was assessed by ELISA. The potential involvement of CK1δ/ε in the above experimental settings was determined using pharmacological (PF670462) and genetic (siRNA) approaches.

Results: CK1δ expression was significantly higher in the airway wall of severe asthmatics compared to well-controlled asthma and healthy subjects. In BEAS-2B cells and ALI-HBECs, TGF-β1 suppression of GCinduced GRE activity and endogenous gene expression was prevented by CK1δ/ε (3μM PF670462). Poly (I:C)/TNF-α-induced pro-inflammatory Introduction/Aim: Improved diagnostic tools for predicting airway inflammatory phenotype and future exacerbation frequency in asthma are required. We previously demonstrated a sputum gene expression signature of 6 biomarkers (6GS) could predict inflammatory phenotype and corticosteroid responsiveness in stable asthma. We recently demonstrated that azithromycin add-on treatment in uncontrolled moderate-to-severe asthma significantly reduced asthma exacerbations (AMAZES clinical trial). We aimed to test whether the 6GS predicts airway inflammatory and future exacerbation phenotypes in a subpopulation of the AMAZES clinical trial. We also tested whether 48 weeks of azithromycin treatment altered 6GS expression compared to placebo.

Methods: 142 patients (73 placebo-treated, 69 azithromycin-treated) produced adequate sputum for differential cell count and PCR of 6GS markers at baseline and after 48 weeks of treatment. Logistic regression and ROC analysis was performed on baseline results to compare the predictive value of 6GS and conventional biomarkers for airway inflammatory phenotype and future exacerbation frequency.

Results: The 6GS significantly predicted airway inflammatory subtype at baseline, outperforming systemic biomarkers peripheral blood eosinophils (PBE) and fractional exhaled nitric oxide (FENO). 6GS significantly predicted future exacerbation phenotype, was numerically superior to all biomarkers examined (sputum eosinophils, sputum neutrophils, PBE and FENO), and identified patients who would go on to experience frequent (≥ 2/year) severe exacerbations. Azithromycin treatment did not significantly alter 6GS expression compared to placebo, nor did it affect the prediction of exacerbation phenotype using the 6GS.

The sputum 6GS is useful as a diagnostic tool for inflammatory phenotyping and predicting future frequent severe exacerbations. The 6GS retains this predictive capacity in azithromycin-treated asthma, suggesting a novel therapeutic mechanism independent of known exacerbation-associated inflammatory factors. Methods: We recruited 10 adults, with poorly controlled allergic asthma; atopic to one or more aeroallergens, on maximal dose inhaled corticosteroid/ long acting bronchodilators, with persisting poor asthma symptom control, exacerbations requiring oral corticosteroids and a serum total IgE >30IU/ml. They were compared to healthy aged matched controls with no asthma or atopy. Participants were assessed prior to commencing treatment with Omalizumab and then 6 months later at the time effectiveness of treatment was assessed. Blood was drawn and peripheral blood monocytes (PBMCs) were isolated. PBMCs were then exposed for 48 hours to IAV, and RV.. Response was assessed by ELISA/bead arraywith release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-6, IL-10, IL-5 and IL-13.

Results: At baseline visit subjects with severe allergic asthma compared to healthy controls demonstrated impaired IFN-α, and IFN-λ release in response to IAV (p<0.001) and RV (p=0.003). Following 6 months treatment, 9/10 demonstrated an improvement in asthma symptom control to continue treatment. In the clinical responders there was a significant increase seen in IFN-α, and IFN-λ to IAV and a trend towards improvement to RV.

Conclusion: Adults with severe allergic asthma demonstrate impaired systemic innate immune responses to IAV and RV. Treatment with Omalizumab, that results in improved asthma control is associated with improvement in innate antiviral responses.

Editorial material and organization © 2018 Asian Pacific Society of Respirology. Copyright of individual abstracts remains with the authors.

Introduction/Aim: Treatable traits (TT) have been proposed as a new approach for airway disease management, however supporting data are currently limited. We aimed to determine if identification of TT is possible using a severe asthma registry, to assess their prevalence in severe compared to non-severe asthma, and to assess the relationship between TT and future exacerbation risk.

Methods: The Severe Asthma Web-based Database is an observational registry of 434 severe asthma patients and a comparison group of 102 patients with non-severe asthma from 26 sites in Australasia (18-88 years, 59% female). Participants were characterised at enrolment and followed for 24 months. Published traits 1,2 were mapped to registry data fields and prevalence determined. Bayesian model averaging was applied to identify traits that best predicted future exacerbation risk.

Results: Seven pulmonary, 13 extrapulmonary and 4 behavioural risk-factor traits were identified. More pulmonary and extrapulmonary traits were expressed in severe than non-severe asthma (p<0.001). Traits significantly more common in severe asthma were incompletely reversible airflow limitation (58% vs. 39%, p=0.002), frequent exacerbations (51% Conclusion: A registry-based systematic characterisation of asthma may be used to assess TT. We report traits that predict exacerbation risk and confirm greater burden associated with severe asthma. Trials evaluating the efficacy and cost-effectiveness of the TT approach are needed. Introduction/Aim: Asthma is a chronic inflammatory airway disease which is characterized by recurrent attacks of breathlessness and wheezing. The pathogenesis of asthma is complex and still unclear. The unfolded protein response (UPR) of the endoplasmic reticulum (ER) has recently been identified as playing a decisive role in inflammatory diseases. Worsening of asthmatic condition can be brought on by stimuli such as oxidative stress, pathogenic infection, and allergen exposure. All of which can induce ER stress and activate UPR. Activated arms of UPR induce different inflammatory pathways and dysregulate the innate immune response. However, how UPR is associated with asthma is unclear. Here we investigate the UPR signature in different inflammatory phenotypes of asthma using human clinical samples.

Methods: Broncho alveolar lavage fluid (BALF), endobronchial biopsies and induced sputum samples were collected from eosinophilic, neutrophilic, paucigranulocytic asthma patients, and from healthy individuals. The expression of UPR associated genes in BALF cells, and biopsy samples were analysed by qPCR. UPR related protein expressions was analysed by immunoblot. UPR gene expression in sputum cells were analysed by microarray.

Results: UPR genes (GRP78, CHOP, XBP1s, and PDIA4) in lung immune cells were significantly induced (p<0.05) in eosinophilic asthma while neutrophilic asthma demonstrated an increased trend. GRP78 and CHOP protein expression were significantly higher in both eosinophilic and neutrophilic groups. Microarray data from sputum cells demonstrated an upregulation of various UPR genes mostly in the eosinophilic asthma group, but not in paucigranulocytic or mixed granulocytic groups. UPR gene expression in lung biopsies did not show significant differences between groups. However, bronchial epithelial cells (BECs) treated with asthma allergens demonstrated an increased trend of UPR.

Conclusion: UPR is heightened in eosinophilic and neutrophilic asthma. Airway immune cells have a major role in regulating UPR in airways of asthma.

Respirology (2018) Hypothesis: We hypothesise that the pro-fibrotic effects of STAT3 involve B cell-mediated immune regulation.

The effect of anti-CD20 therapy in bleomycin-treated wildtype and gp130 757F mice on lung fibrosis and immune cell composition was examined. Mice were given two 100μg doses of anti-CD20 antibody (Genentech Inc USA) or IgG2a isotype control i.p. either 7 days prior to and 7 days after bleomycin or on day 10 and day 19 post-bleomycin treatment (following the initiation of fibrosis), and the extent of fibrosis measured at 28 days.

Results: FACS analysis of blood taken on days 0, 7 and 28 days post-bleomycin-treatment revealed an almost complete depletion of CD19 + B cells in the circulation of wildtype mice but not gp130 757F . However, the extent of fibrosis, assessed using micro-CT imaging and HPLC analysis of hydroxyproline levels was not significantly different between treatment groups. Histological analysis revealed an abundance of CD5+ B cells and CD138+ (plasma cells) in the lungs of the anti-CD20-treated mice. FACS analysis identified an expansion of CD138+ (days 7 and 28) and CD5+ cells in the lungs of bleomycin treated mice at day 28.

Conclusion: Although antibody depletion of follicular B cells had no effect on bleomycin-induced fibrosis, residual CD138+ plasma cells and CD5+ B are abundant in the lungs of bleomycin-treated mice. The activity of these B cell subsets may contribute to the fibrotic phenotype. Introduction: Class III NAD-dependent histone deacetylase (HDAC) sirtuin 1 (SIRT1) is an important regulator of senescence, aging and inflammation through de-acetylation of chromatin histones thereby silencing inflammatory gene transcription. We have reported increased steroid resistant senescent pro-inflammatory CD28nullCD8+ T cells in patients with COPD. We hypothesized that expression of SIRT1 would be reduced in these cells in COPD and that treatment with SIRT1 activators (resveratrol) and agents that prevent NAD depletion (theophylline) would upregulate SIRT1 expression and reduce pro-inflammatory cytokine expression in these steroid resistant cells.

Methods: Blood was collected from COPD patients and aged matched controls and expression of CD28, SIRT1 and pro-inflammatory cytokines determined in CD8+ and CD8-T and NKT-like cells cultured in the presence of AE 1μM resveratrol AE 5.0mg/mL theophylline AE 1 μM prednisolone using flow cytometry.

CD28nullCD8+T and NKT-like cells compared with CD28+ counterparts from both patients and controls (eg., CD28null 7AE3% vs. CD28+ 55AE5%).

Loss of SIRT1 was associated with increased production of IFNγ and TNFα and steroid resistance. SIRT1 expression was upregulated in the presence of 1μM resveratrol and 5.0mg/mL theophylline and was associated with a decrease in steroid resistance and IFNγ and TNFα production by CD28nullCD8+T and NKT-like cells.

Conclusion: Steroid resistance in pro-inflammatory CD28nullCD8+ T and NKT-like cells is associated with decreased SIRT1 expression. Combination resveratrol and/or theophylline treatment increases SIRT1 expression, restores steroid sensitivity and inhibits pro-inflammatory cytokine production from these cells and may reduce systemic inflammation in COPD.

Grant Support: Introduction/Aim: Women have a higher incidence of asthma compared to men and exacerbations in women are often more severe and correlate with high estrogen levels. Using an experimental animal model for asthma, we have observed that female rats with experimental asthma also develop more severe exacerbations compared to male rats. The aim of the study was to investigate if the female sex hormone estrogen can impact the asthma response and identify the immunological mechanism for this effect.

Methods: By implanting estrogen-releasing pellets into male rats prior to ovalbumin-sensitisation and re-challenge we investigated how estrogen-exposed males responded compared to untreated males and females. We used multi parameter flow cytometry to investigate proportion and activation of antigen presenting dendritic cells, responding T effector and regulatory T cells in airways before and after allergen rechallenge.

Results: We discovered that estrogen was sufficient to induce a female-like disease phenotype during exacerbations in male rats. Interestingly, male and female rats also displayed significant differences in CD4 +/CD8+ T cell ratios in airway draining lymph nodes and this was directly impacted by estrogen exposure. In addition, female and estrogen treated male rats, but not male rats, displayed signs of recruitment of CD4+ cells into the airways following allergen re-challenge which most likely contributed to the exacerbated response.

Conclusion: Our data suggest that estrogen is sufficient to induce female like asthma symptoms in male rats and appears to alter the T cell balance promoting allergic responses. Grant Support: The study was funded by the Asthma Foundation of Western Australia, the Telethon Kids Institute and the Swedish Society for Medical Research.

Introduction and Aims: Small molecules can correct CFTR production or function and greatly improve CF outcomes. Rarer mutations are hindered by the lack of appropriate primary culture models. Modifying primary airway epithelial cells (AECs) from children with CF modified to express a fluorescence marker that allows functional CFTR assessment would provide a culture-based high-throughput screening platform. We compared methodologies to achieve stable fluorescence in primary AEC.

Methods: Primary AECs were obtained from children (CF and non-CF) by bronchial brushing and cultured using a conditional reprogramming methodology. Cells were transfected with a pcDNA3.1 plasmid via Lipofectamine ® or Nucleofector™ device. Alternatively, AEC were transduced by a replication-deficient retroviral vector with fluorescent tag. After 48 hours, cells expressing fluorescence were selected by fluorescence activated cell sorting (FACS) flow cytometry and then expanded further in culture to assess stability of gene expression.

Results: Primary AECs were amenable to all three methodologies.

Transfection by Lipofectamine ® was 24.1% efficient and the best electroporation protocol achieved a slightly higher efficiency (30.0%). Replication deficient retrovirus was most effective with 78.9% positive cells. There was no difference in transfection efficiency observed between non-CF and CF AECs. Cells could be successfully cultured after FACS selection, but only AEC transduced by retroviral vector maintained their fluorescence through two passages of cultures. is the second leading cause of avoidable hospital admission in Australia, but to date no national data exists that compares the recommendations of clinical practice guidelines for inpatient management of acute exacerbations against actual practice. We aimed to compare contemporary management against the recommendations of the COPD-X guidelines.

Methods: A prospective audit of COPD hospital admissions from five tertiary care hospitals in five states in Australia was conducted. A standardised audit tool was used to collect data. Telephone follow-up at 28 days after discharge assessed readmission and health-status. Data were assessed against the COPD-X guidelines.

Results: Prospective data were obtained for 207 admissions in 171 patients between October 2012-April 2013. The meanAESD age was 70.2AE9.9 years, 50.3% were male, and 95.3% caucasian. The mean number of comorbidities per patient was 3.6AE1.9, with hypertension (48.5%), gastrointestinal disease (37.5%), ischaemic heart disease (28.5%), psychiatric/anxiety/depression disorders (28.1%) the most prevalent. Over half were ex-smokers (58.6%) and lived at home with another (56.2%). Of the 171 patients, 21.1% were readmitted within 28 days, there were 2 inpatients deaths (1.2%), and a further 9 deaths (5.3%) within 28 days of discharge.

Concordance to the COPD-X recommendations varied. Prescription of oral corticosteroids ( Introduction: The FLAME study demonstrated the superiority of indacaterol/glycopyrronium (110/50 μg, once daily), in reducing exacerbations, improving lung function, and health status versus salmeterol/fluticasone in moderate-to-very severe COPD patients with a history of exacerbations. 1 We assessed the effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on the rate and risk of moderate or severe exacerbations in a subset of GOLD Group D patients who had a history of ≥2 exacerbations or 1 hospitalization for exacerbation from the FLAME study.

Methods: FLAME was a 52-week, randomized, double-blind, doubledummy, parallel-group study. Patients with moderate-to-very severe COPD, post-bronchodilator FEV 1 ≥25% to <60% predicted normal, and a history of ≥1 exacerbation in the previous year were randomized (1:1) to receive either indacaterol/glycopyrronium (110/50 μg) once-daily or salmeterol/fluticasone (50/500 μg) twice-daily. The rate and time to moderate or severe exacerbations were analyzed in the subset of GOLD Group D patients.

Results: Of the 3362 patients randomized, 2514 were categorized as GOLD Group D. The mean post-bronchodilator FEV 1 was 44.1% of the predicted normal value and 56.3% patients were on ICS at screening.

Indacaterol/glycopyrronium demonstrated superior efficacy over salmeterol/fluticasone in reducing the rate of moderate or severe exacerbations (rate ratio, 0.86; Table) . Indacaterol/glycopyrronium delayed the time-tofirst moderate or severe exacerbation compared with salmeterol/fluticasone (median days: 291 versus 215; Table) . The patients treated with indacaterol/glycopyrronium had a 19% lower risk of a moderate or severe exacerbation compared with salmeterol/fluticasone. Conclusion: Indacaterol/glycopyrronium was superior to salmeterol/ fluticasone in reducing the rate and risk of moderate or severe exacerbations in subset of GOLD Group D patients with a history of ≥2 exacerbations or 1 hospitalization for exacerbation, confirming its use as a preferred treatment option for COPD patients at high risk of exacerbations.

Grant Support: Novartis Pharma AG, Basel University of South Australia, Adelaide, South Australia, Australia

Introduction: Familial aggregation of chronic lung conditions may result from a combination of genetic susceptibility and exposure to risk factors throughout life. We used a life-course approach to investigate factors contributing to the relationship between parental respiratory disease history and Reduced Lung Health (RLH) in adulthood using data from the 1958 British Birth Cohort Study.

Methods: Cohort participants (n=6304) were characterised in terms of RLH (presence of respiratory symptoms at 42yrs and airway obstruction [FEV1/FVC<0.7 at 45yrs]) and parental history of respiratory disease (at offspring age 0,11,16yrs).

Life-course factors evaluated were maternal smoking (0yrs), living with smoker (16,23,33,42yrs), social class (0,7,16,23,33,42yrs), respiratory illness (7,11,16,23,33,42yrs) , smoking status (23,33,42yrs), and occupational exposure to dust or fumes (33,42yrs), operationalised for life periods (birth, childhood [7,11,16yrs], adulthood [23,33,42yrs] ). Path analysis was used to investigate the mediating role of life-course factors in the relationship between parental respiratory disease history and RLH, adjusting for gender, asthma and recent chest infection.

Results: Within this cohort, 3.7% had a parental respiratory history and 6.3% of offspring had RLH. Parental respiratory history was positively associated with RLH (p=0.023). Maternal smoking during pregnancy, personal smoking in adulthood, social class (0, 23 and 42yrs) and occupational exposure to dust or fumes were the only factors related to both parental history and RLH. Mediating pathway testing indicated that the sequence through maternal and adulthood smoking contributed most to model fit (indirect effect p=0.015), explaining 30% of the parental history-RLH relationship.

Conclusion: An association between parental history of respiratory disease and offspring RLH at 45yrs was partly mediated by a sequence of exposure to maternal smoking and being a smoker during their adulthood. A large proportion of the relationship between parental history-RLH remains unexplained by smoking, suggesting that assessing parental history of respiratory disease may provide insights into earlier diagnosis and intervention.

Grant Support: Australian Government Research Training Program Scholarship (LSK Li) enced by each of these pathophysiological phenomena, but is also dependent on lung volume. In the presence of airway closure, where oscillating pressure waves are not able to penetrate all lung segments, X5 may not relate to the total thoracic gas volume. Single-breath alveolar volume (VA), measured during the diffusing capacity test, estimates the communicating gas volume by dilution during a breath hold. The ratio of VA to plethysmographic total lung capacity (TLC), or VA/TLC, is therefore reduced in obstructive airways disease due to incomplete gas mixing and gas trapping. We hypothesised that X5 would relate to VA/TLC but not TLC in COPD.

Methods: 15 subjects with mild-moderate COPD (11 male, mean (range) age 68 (58-79), mean AE SD %pred FEV1 64 AE 17) were tested using FOT (Thorasys tremoFlo c100) during 60 s normal tidal breathing. Spirometry, body plethysmography and the single-breath diffusing capacity test were then performed according to standard quality criteria. Spearman rank correlation coefficients were determined before and after adjustment for known covariates from published reference equations.

Results: X5 was moderately correlated with VA/TLC (r = 0.66, p = 0.008) and VA (r = 0.58, p = 0.03) but not with TLC. After adjustment for known covariates, X5 Z-score remained moderately correlated with VA/TLC (r = 0.60, p = 0.02) but not VA or TLC Z-scores. VA/TLC correlated with the severity of airflow obstruction measured by FEV1/FVC ratio Z-score (r = 0.77, p = 0.001).

Conclusion: In COPD, X5 measured by FOT during normal tidal breathing reflects the communicating lung volume rather than the total lung volume. FOT therefore may compliment traditional lung function measurements. Introduction/Aim: The six minute walk test (6MWT) remains the most commonly used clinical measure of exercise capacity in pulmonary hypertension (PH). Whilst maximal exercise testing using a cardiopulmonary exercise test (CPET), remains the gold standard estimate of exercise capacity, this test is much less common in clinical practice. The purpose of this study was to compare the physiological responses to the 6MWT and CPET in a group of PH subjects.

(Functional Class I-III) completed a CPET on a cycle ergometer and a 6MWT on separate days. During both tests, gas exchange was measured using a calibrated portable metabolic system (Cortex, Metamax). Oxygen uptake (VO 2 ), carbon dioxide production (VCO 2 ), ventilation (V E ), heart rate (HR), oxygen (O 2 ) pulse, V E /VCO 2 , end tidal carbon dioxide (P ET CO 2 ), oxygen saturation (S P O 2 ) and breathlessness (Borg, 0-10) were averaged over the final 30s and compared between the 6MWT and CPET. In a subgroup of 8 participants, end exercise lactate (HLa) was also measured using a portable lactate analyser (Lactate Scout).

The mean peak power achieved by participants was 74 AE 20 W, whilst the mean 6MWT distance was 574 AE 89m. There was no significant difference between CPET and the 6MWT for peak VO 2 (CPET: 16.3AE6.6 vs 6MWT: 15.5AE3.8 ml.kg -1 .min -1 ), V E (54.7AE13.8 vs 49.7AE15.8 L.min -1 ), HR (136AE22 vs 143AE27 beats.min -1 ), O 2 pulse (6.8AE1.3 vs 7.0AE1.7 ml.beat -1 ), V E /VCO2 (35AE6 vs 36AE5), P ET CO 2 (30AE5 vs 29AE4 mmHg) or SpO2 (88AE11 vs 87 AE 14%). Peak VCO 2 (1.43AE0.46 vs 1.20AE0.31 L.min -1 ), breathlessness (5.5AE2.2 vs 3.6AE1.9) and lactate (8.5AE1.5 vs 5.0AE1.9) were all significantly higher(p<0.05) with CPET.

We found that the physiological responses to CPET and 6MWT in our group of PH participants were similar. This would suggest that the 6MWT is similar to a peak exercise challenge the PH population. Introduction/Aim: In pulmonary rehabilitation (PR), cycle training is recommended at 60% peak oxygen uptake measured during cardiopulmonary exercise testing (CPET). However, access to CPET is limited and estimation of an equivalent intensity from the 6-minute walk distance (6MWD) using published equations is associated with substantial variation. This study aimed to investigate whether a submaximal cycle exercise test (SMCT) can prescribe appropriate cycle training intensity and whether initial training intensity estimated from 6MWD and SMCT is similar.

Methods: Retrospective data was collected from patients who attended PR over the previous 12 months. Each patient routinely performed a 6-minute walk test at baseline and completed a SMCT during the second exercise session. In the subsequent exercise session, cycle training was prescribed at 50% of peak work (Watts) achieved on SMCT. Initial intensity was considered appropriate if the patient could complete 15 minutes as prescribed with a reported dyspnoea and/or RPE score of 3-4 on the Borg 0-10 score.

Results: Forty-three patients (23 male) with chronic lung disease (23 COPD, 10 ILD, 10 other) were included, with mean (SD) age of 70(11), 6MWD 437(86) metres and SMCT peak work of 60(22) watts. Eight one percent of patients achieved the target intensity, 16% found the initial workload too easy and 2% were unable to maintain the target intensity. There was a moderate correlation between work rate predicted from 6MWD 35(8) Watts and SMCT 30(11) Watts (r= 0.71, p<0.001). Estimating cycle training intensity from 6MWD over-predicted (>5 Watts) appropriate training in 44% patients and under-predicted in 7%.

In chronic lung disease, prescribing cycle exercise intensity at 50% of SMCT peak work achieves an appropriate training intensity that was tolerated by > 80% of patients. Prescribing work rate from SMCT and 6MWD results in similar training loads, although SMCT may provide more accurate cycle training intensity. Introduction/Aim: Increased dietary fat is associated with an increased risk of asthma and airway hyperresponsiveness. A single high fat meal reduces the efficacy of salbutamol, suggesting that dietary fatty acids may alter airway smooth muscle (ASM) contractility. Therefore our aim was to determine the effect of fatty acids on in vitro bovine trachealis smooth muscle responsiveness to relaxant and contractile stimuli.

Methods: Oleic acid, linoleic acid, alpha-linolenic acid, palmitic acid, stearic acid and elaidic acid were compared at 10 -4.5 M. Bovine trachealis muscle strips (n = 7/group/experiment) were mounted in tissue baths with warmed, aerated Krebs solution. All experiments were done in the presence of tetradotoxin (10 -6 M). To test sensitivity to relaxant stimuli, muscle strips were contracted with acetylcholine (half maximal effective concentration, EC 50 ) before addition of vehicle or fatty acid and cumulative doseresponse curves to isoproterenol (10 -9 M to 10 -4 M) performed. To test sensitivity to contractile stimuli, separate muscle strips were incubated with vehicle or fatty acid for 20min before cumulative dose-response curves to acetylcholine (10 -9 M to 10 -2 M) were performed.

Results: In the relaxation experiment, ASM force following acetylchoine was not affected by addition of any of the fatty acids. Similarly, there was no effect of fatty acid on the EC 50 concentration to isoproterenol (RANOVA p = 0.52). In the contraction experiment, baseline force was unaltered by addition of any of the fatty acids. Similarly, there was no effect of fatty acid on the EC 50 to acetylcholine (RANOVA p = 0.86).

sensitive ultra-performance liquid-chromatography with tandem massspectrometry assay for quantification of PIP/TAZ.

Methods: Both drugs were extracted from human plasma and pleural fluid by protein precipitation in methanol containing internal standards (IS) piperacillin-d 5 and sulbactam. 5uL of sample was mixed with 125uL of methanol containing IS, vortexed and centrifuged. Supernatant was diluted into mobile phase containing 10mM of ammonium bicarbonate and water. The chromatographic separation was achieved using an Acquity BEH C-18 column.

This method was applied to two patients with pleural infection. Six pleural fluid and blood samples were obtained at steady-state before and over 6-hours post-infusion of 4500mg-PIP/TAZ. selectivity, specificity, precision, accuracy, matrix effects and stability; results were within acceptable limits.

In both patients, the time to maximum concentration (C max ) for PIP and TAZ in pleural fluid were delayed compared to plasma. The C max for PIP in pleural fluid reached 63mg/L and 59mg/L at 90 and 150-minutes in each patient. This was 77% and 52% of the C max achieved in plasma for each patient respectively. Introduction/Aim: Bronchiectasis not related to cystic fibrosis (non-CF BEx) is an increasingly recognised cause of chronic lung disease that can occur in isolation or with other lung diseases including asthma and COPD. In other settings bronchiectasis is associated with significant health care utilisation but its impact in both Australia and New Zealand is poorly understood, including for Indigenous populations. We aimed to described the impact of non-CF BEx on inpatinet hospital care in this setting Methods: A multicentre Australian and New Zealand retrospective audit of hospital admission data relating to patients with non-CF BEx admitted once or more to five hospitals in Melbourne, Sydney and Alice Springs (Australia) and Auckland (New Zealand) was undertaken. The number and length of stay (LOS) of respiratory admissions was determined. For Melbourne, Alice Springs and Auckland additional information was obtained regarding the requirement for ventilatory support.

Results: Data regarding hospitalisation are presented below.

Conclusion: Health care utilisation for non-CF BEx is substantial.

The number of admissions varies substantially by site as does the cummulative LOS. Average LOS also varies and Australian patients have longer LOS compared to NZ patients. Indigenous Australian patients have a

shorter LOS compared with non-Indigenous counterparts despite more frequent admission and overall greater hospitalisation days. LOS is comparable to COPD (ranging from 4.1-7.3 days in Australia) and the frequency of admission for non-CF BEx is likely to be the major factor driving hospital-based health care utilisation. The utilisation of ventilatory support varies by country and is particularly high in Indigenous Australians. The impact and optimal level of admission frequency, LOS and ventilatory support on susequent representation to hospital, quality of life and survival should be a focus of further investigation. Introduction/Aim: Severe influenza infection in children with chronic lung diseases results in, unscheduled hospital presentations and substantial burden to the health system. National influenza burden data in children with chronic lung diseases are limited. Such data are crucial to monitor burden of disease and evaluate effectiveness of influenza vaccination program. We conducted a retrospective population-based cohort study to measure the impact of influenza on hospitalisation rates in children with chronic lung diseases.

We performed a retrospective cohort study using population-based linked administrative data for all children born in New South Wales between 2001-2010 with complete follow-up until December 31st 2011. The cohort was divided in to two groups: i) children with chronic lung diseases including all children with asthma, bronchopulmonary dysplasia, cystic fibrosis, and congenital lung disorders; and ii) all other standard-risk children.

The primary outcome was any episode of influenza associated hospitalisation (ICD codes J.09-J11). Incidence rates for influenza hospitalisation were calculated for 2001-2011. We used Poisson estimation to calculate 95% confidence interval around incidences.

Results: Our cohort comprised of 9,708 children with chronic lung diseases and 877,240 standard-risk children. The adjusted rate/1000 child-years of influenza hospitalisation in children with chronic lung diseases was 5.21 (95% ) and for all other standard-risk children was 0.92 (95% CI 0.46-1.38). During 2001-2011, the rate in children with chronic lung diseases ranged between 0.20-12.57/1000 child-years. The rate/1000 child-years was similar in male and female children with chronic lung diseases and was 5.45 (95% CI 2.63-8.26) for boys and 5.15 (95% CI 2.41-7.89) for girls.

Our study has demonstrated that children with chronic diseases are at least five times more at risk of being hospitalised with influenza than standard-risk children. Future studies investigating the effectiveness of universal vaccination program for these and all other children may help reduce the burden. can compromise asthma control and increase burden of disease, especially among those with poorly-controlled symptoms. This study assessed perception of control and dependence on reliever medication among patients who were taking SABA alone.

Methods: Cross-sectional population-based internet survey of participants with current asthma aged >16 years. Using Likert-type questions (ranging from strongly disagree to strongly agree), the survey captured attitudes about asthma and asthma treatment. Asthma control was assessed using the Asthma Control Test (ACT: Poorly-controlled <20; Well-controlled 20-25).

Results: SABA-only respondents who had poor symptom control (n=374) compared with SABA-only users with well-controlled symptoms (n=632) were almost 3 times more likely to agree/strongly agree that they felt anxious without a reliever when out (30.6 vs. 11.6%, respectively; p<0.0001), and almost twice as likely to feel anxious when without a reliever around triggers (36.9 vs. 19.2%, respectively; p<0.0001). Additionally, those with poorly-controlled vs. well-controlled symptoms were more likely to agree/strongly agree that they relied on their reliever for their asthma (50.9% vs. 39.9%, respectively; p<0.0001), and that their reliever was "a life-saver" (43.6% vs. 24.4%, respectively; p<0.0001). Half of respondents in both groups agreed/strongly agreed that their reliever gave them control over their asthma (49.7% vs 52.2%, respectively; p=0.74).

Conclusion: Patients with poor symptom control appeared overly reliant on SABA compared to patients with well-controlled asthma. While optimal asthma control in this population requires preventative treatment, half of SABA-only respondents viewed their reliever as their means of achieving control over their asthma. Given this, public messages such as "you can control your asthma" that are aimed at encouraging preventer use may inadvertently give the opposite message to many people. These data call into some question the preventer-reliever-control paradigm as currently used. Terminology that interacts better with patients' thoughts and beliefs may be more effective. Weights of offspring were recorded until 8 weeks of age at which point they were euthanized and a tracheasectomy was performed. Trachea segments were studied in an organ bath chamber to measure isometric force production to carbachol and subsequently fixed for morphometry.

Maximal active tension and stress were calculated from force normalised to segment length and ASM cross-sectional area respectively.

Results: The IUGR offspring were lighter at birth (Control, n=60;

IUGR, n=58; p<0.05) and remained lighter at 8 weeks of age compared with Controls (Control, n=21; IUGR, n=21; p<0.05). Active tension (p<0.05) and stress (p<0.05) were reduced in male IUGR offspring compared with Controls with no difference in ASM thickness. There were no statistical differences in active tension or stress in IUGR female offspring despite a reduction in ASM thickness (p<0.05). Sensitivity of ASM to contractile agonist was not altered by IUGR.

Conclusion: There are persisting effects of IUGR on the mature airway wall which favour reduced contraction of the ASM layer, including lower ASM contractility in male offspring and a thinner ASM layer in female offspring. Findings suggest that altered development of the fetal airway can impact susceptibility to future airway disease through changes in ASM structure and function. Contraction of the airway smooth muscle (ASM) layer in the absence of an exogenous stimulus is termed 'intrinsic tone' and may contribute to airflow limitation. The aim of this study was to assess the underlying structural determinants of ASM intrinsic tone in peripheral human airways.

Methods: Subjects (12M:6F, 37-85 years) undergoing lung resection surgery were recruited and baseline lung function assessed prior to surgery. Peripheral airways were dissected from resected tissue and further cut into bronchial rings (1-4 rings/subject) for measurement of force in organ bath chambers. Length-tension curves were constructed to KCl (60 mM) to establish optimum length (L O ) for contraction and subsequently adapted to repeated KCl stimulation. All experiments were performed at L O. Tension (mN/mm) in the ring was determined before and after complete relaxation to theophylline (10 -2 M) and then fixed for stereology. Sections (0.5 μm) were stained using Masson's trichome technique and relative fractions of ASM (VV ASM ) and ECM (VV ECM ) within the ASM layer measured by point counting. Muscle tension was converted to stress (mN/mm 2 ) after normalising to muscle thickness.

Results: Subjects had a pre-bronchodilator FEV 1 (%Pred) of 89.4AE4.5 and FEV 1 /FVC of 0.72AE0.03. Bronchial rings exhibited a mean intrinsic stress of 20.1AE3.4mN/mm 2 . Intrinsic stress (n=18) was negatively correlated with VV ECM (r=-0.47, p<0.05) and positively correlated with VV ASM (r=0.51, p<0.05). There was also a non-significant trend for a decrease in FEV 1 (%Pred) with increasing intrinsic stress (r=-0.56, p=0.07). There was no association between lung function and VV ECM or VV ASM .

The presence of intrinsic stress in the peripheral ASM layer is determined by the underlying layer composition, increasing with greater muscle fraction and decreasing with ECM fraction respectively. We propose that muscle composition affects lung function through regulation of intrinsic tone. 1, 3 , SHIVAPPA N 4, 5, 6 , HEBERT J 4, 5, 6 , HODGE A 1, 7 lung function and, in turn, the development and/or progression of chronic inflammatory lung diseases. Few studies have assessed the relationship between the dietary inflammatory index (DII ® ), a literature-derived measure of the inflammatory potential of the diet, and lung function. We aimed to investigate this relationship in a population-based sample of middleaged adults.

Methods: A random sample of middle-aged adults (45-72 years) from inner south-east Melbourne were assessed by spirometry and questionnaires (n=1183). An energy-adjusted DII was calculated for each participant from a semi-quantitative food frequency questionnaire. Regression methods were used to model relationships between DII quintiles and lung function outcomes, adjusting for age, gender, height, energy intake, BMI, asthma, atopy and smoking. Asthma status was also examined as an effect modifier.

Results: Associations between DII and FEV 1 and between DII and FVC differed by asthma status (p=0.001 and <0.001, respectively). Current asthmatics with a diet in the highest DII quintile had a mean FEV 1 516ml lower than those in the lowest DII quintile (95%CI 212, 819ml; P trend =0.003) and a mean FVC 588ml lower (95%CI 249, 926ml; P trend =0.006). Remitted asthmatics with a diet in the highest DII quintile had a mean FEV 1 364ml lower than those in the lowest DII quintile (95% CI 81, 646ml; P trend =0.02) and a mean FVC 391ml lower (95%CI 76, 706ml; P trend =0.01). For those who had never had asthma, there were no associations between DII and any of the lung function measures. There were also no associations between DII and FEV 1 /FVC in any asthma category.

Conclusion: A pro-inflammatory diet was associated with poorer lung function in current and remitted asthmatics. If this association is causal, it argues for a low inflammatory diet for people with a history of asthma. Introduction/Aim: Vocal cord dysfunction (VCD) is often mistaken for severe asthma and accurate diagnosis is crucialbut difficult. Treatment is complex and dedicated follow-up is essential. To examine optimal overall management of VCD a Multidisciplinary Team (MDT) clinic was initiated and operationalized. This type of clinic has not yet been described.

Methods: Patients with suspected VCD (n=80) were referred by Respiratory physicians (n=76) and ENT surgeons (n=4). The clinic was staffed by a Respiratory physician, ENT surgeon (laryngologist), Speech therapist and Respiratory Nurse specialist. Patients completed questionnaires, had spirometry and dynamic CT larynx prior to review. At review by the team a history was obtained, physical examination conducted and laryngoscopy performed. Diagnosis of VCD was based on detection (CT larynx or laryngoscopy) of inspiratory paradoxical vocal cord movement (PVCM) on at least one occasion. The team finally reviewed all data, a likely diagnosis was formulated and treatment was selected in consultation with the patient.

Results: A total of 80 patients are reported of whom 61 (76%) had established asthma. A diagnosis of VCD was established in 53/80 cases (67%) and 44 elected to access speech therapy services. Based on symptoms speech therapy was gauged unsuccessful in 29/44 patients (65%) and 22/29 individuals elected to have botulinum toxin injection. In a second group of 17/80 cases (21%) a diagnosis of VCD was considered unlikely. In this group 13/17 patients had poorly controlled asthma and 4/17 patients had other diagnoses. In a third group of 10/80 patients (12%) VCD was strongly suspected but not confirmed. All patients were offered speech therapy and success was achieved in 7/10 cases.

Conclusion: A VCD MDT clinic was established providing an integrated multidisciplinary approach to diagnosis and management of VCD. Our experience indicates that this strategy is feasible and can be employed to optimise management of this problematic condition. Introduction/Aim: Treatable traits have been proposed as a new paradigm for airway disease management. Our aim was to determine the prevalence of traits in severe asthma and COPD compared to healthy controls and to compare trait prevalence by diagnostic label.

Methods: Participants with severe asthma, COPD and age-matched healthy controls were recruited to this cross sectional study and underwent a clinic-based multidimensional assessment to characterise their treatable traits.

Results: Recruited were 140 severe asthma, 45 COPD and 67 healthy control participants. Overall the meanAESD age was 56.6AE16.2 years, and 57.5% were female. COPD participants were older compared to those with severe asthma and healthy controls, p<0.001. Post-bronchodilator FEV 1 % predicted was lower in COPD (53.0AE19.8) compared to severe asthma (74.7AE21.1) and healthy controls (99.0AE13.8); p<0.001. Of the 23 possible traits, significantly more were identified in COPD (10.6AE2.4) and severe asthma (9.0AE2.8) compared to healthy controls (2.4AE1.4); p<0.001, with a significant difference between COPD and severe asthma; p< 0.001. However, the number of comorbidities was not different between disease groups (COPD 6.8AE3.1 versus severe asthma 5.9AE2.7). Traits that were more prevalent in COPD compared to severe asthma were dyspnoea; p<0.01, exertional O 2 desaturation; p<0.001, mucous-hypersecretion; p<0.05 and airflow limitation; p<0.001. Those with severe asthma had significantly more daytime-sleepiness; p<0.01, musculoskeletal problems; p<0.01, obesity; p<0.05, upperairway diseases; p<0.001 and dermatitis; p<0.001. Airway-eosinophilia was more common in severe asthma and airway-neutrophilia and systemic inflammation in COPD, p<0.05, p <0.001, respectively. The prevalence of frequent chest infections, pathogen colonisation, smoking, nonadherence, inhaler-polypharmacy, dysfunctional breathing, reflux, anxiety or depression did not differ between COPD and severe asthma.

Conclusion: This study confirms the heterogeneity of COPD and severe asthma. Multidimensional assessment in chronic airway disease allows for the detection of traits that can be targeted using a precision medicine approach. Trials testing these approaches are needed to advance management. Introduction/Aim: Increasing evidence highlights that cellular senescence contributes to idiopathic pulmonary fibrosis (IPF). The DNA damage response (DDR) in senescence also leads to escalated mitochondrial superoxide production to reinforce senescence. This study characterises senescence in lung fibroblasts from IPF patients (IPF-LFs) and age-matched controls (Ctrl-LFs), delineating the role of mitochondria in senescence stabilization.

Methods: Fibroblast senescence was assessed using a composite set of markers, including p21 expression and senescence-associatedβ-galactosidase activity, which were measured by PCR and cytochemical staining, respectively. The DDR was detected by formation of phosphorylated-p53 nuclear foci using immunofluorescence. A senescent-associated secretory phenotype (SASP) was characterised by measuring increases in cytokine production and inflammatory gene expression with ELISA and Nanostring technology, respectively. Mitochondrial dysfunction was monitored by increases in mitochondrial stress, mass and superoxide using the fluorogenic dyes, n-nonyl-acridine orange, Mitotracker Green and MitoSOX, respectively.

Results: Even at early passage, IPF-LFs were more senescent-like than Ctrl-LFs, exhibiting an intensified DDR, a SASP and mitochondrial dysfunction. The DNA damaging agent etoposide augmented senescence in Ctrl-LFs accompanied by heightened mitochondrial stress, mass and superoxide production. However, it had no effect on IPF-LFs. Mitochondrial perturbation by rotenone also evoked a DDR and senescence in Ctrl-LFs. Inhibition of mTORC1, a regulator of mitochondrial function or incubation with the antioxidant, N-acetyl cysteine attenuated pharmacological-induced senescence. were carried out to identify basal differences in expression of ECM and epigenetic gene targets between COPD and non-COPD smokers. qPCR carried out to confirm microarray analyses and determine effect of epigenetic inhibitors.

Results/Conclusion: ASM cells from COPD patients show augmented col5a1, col15a1 and TNC expression in response to stimulation with TGF-β (10ng/mL) when compared to cells of smokers without COPD. Inhibition with TSA had no effect on col5a1, or TNC expression in cells from both patient groups, whilst inhibiting col15a1 expression in COPD.

(+)JQ1 treatment significantly abrogated expression of col15a1 COPD and non-COPD groups, whilst col5a1 expression was abrogated in COPD and TNC in non-COPD. Col5a1 expression was significantly repressed with Curcumin treatment in non-COPD group only. The different responses between non-COPD susceptible smokers and COPD group highlights the epigenetic differences in disease, and that targeting histone acetylation may be a therapeutic option of small airway fibrosis in COPD. . No significant differences were seen in any sleep parameter (SOL, TST, WASO, SE) after PR (all p>0.10), between intervention groups (all p>0.20), or within PR groups (all p=0.13). There was no association between sleep parameters and measures of quality of life or function before or after PR. Attendance at a greater proportion of PR sessions was moderately associated with more TST at end rehabilitation (r s =0.5, p=0.009).

Conclusion: Sleep quality, measured objectively using actigraphy, did not improve after an 8-week PR programme in individuals with COPD. Whether ongoing participation in regular exercise training beyond the duration of PR may influence sleep quality is yet to be determined. (Table) .

Conclusion: Using exacerbation history alone (GOLD 2017), rather than combined with lung function, results in more patients classified as GOLD A/B, leading to more statistical power to investigate differences between T+O and monotherapies. Using the 2017 strategy, T+O had a greater impact on SGRQ and TDI than monotherapies in GOLD A/B patients. which showed a reduced loss in FEV 1 in a subgroup of patients, current guidelines recommend treatment with A 1 -PI when FEV 1 is between 30 and 65% predicted. However, the relationship between the effect of treatment on lung structure preservation and FEV 1 is unclear. The aim was to assess the effect of treatment in relation to baseline FEV 1 % predicted as measured by change in computed tomography (CT) lung density in 180 patients randomized in RAPID with baseline FEV 1 between 27% and 79% predicted.

Methods: Changes in annual CT lung density decline rates for both active and placebo treated patients were calculated at 2 years. A random slope intercept model with baseline FEV 1 and treatment group as covariates was used to analyse the influence on treatment effect.

Results: Baseline lung function impairment did not affect long-term changes in lung density (p=ns), the regression line was flat. Active treatment was associated with lung density preservation (P<0.0001) and the regression line was parallel to that of placebo treated patients. The regression line for rate of annual lung density decline vs baseline FEV1% was flat with no interaction between treatment group and baseline FEV 1 .

Conclusion: These data demonstrate that patients with AATD who are treated with A 1 -PI therapy derive an equal benefit in terms of lung tissue preservation over 2-years that is independent of their pre-treatment FEV 1 %. Grant Support: The RAPID trial programme and preparation of this abstract was supported by CSL Behring.

Editorial material and organization © 2018 Asian Pacific Society of Respirology. Copyright of individual abstracts remains with the authors. Introduction/Aim: Forceps biopsy through a guide sheet after locating the lesion using radial probe EBUS is an established technique in diagnosis of solitary pulmonary modules (SPN). The yield, however, drops significantly if the lesion is not concentric. Furthermore, the 1.7mm forceps often provide small samples which occasionally fall short of providing all the information required in malignancies. Using a cryoprobe in combination with radial EBUS could potentially provide larger samples and increase the yield in non-concentric lesions.

Methods: All patients who underwent radial EBUS cryobiopsy for diagnosis of SPN at Concord and Macquarie University hospitals in Sydney were included in this study. A retrospective audit was undertaken to obtain demographic, baseline physiological and procedural data. Complications and length of stay were recorded. Yield was determined by histopathology and clinical data.

Results: A total of 9 patients (3 female, mean age 73.4 years) have so far been included in the study. All procedures were performed under general anesthesia, with rigid intubation used in 8 cases. The lesion was located in all cases using an EBUS radial probe with only one eccenteric lesion. Most targets were located in the upper lobes (66.6%). An average of 3.1 biopsies were obtained. No cases of pneumothorax or severe bleeding were observed. Only two patients stayed overnight after the procedure. Average diameter of specimens was 5mm. Definite malignant pathology was diagnosed in 5 cases with an overall yield of 7/9 (77.7%) Conclusion: Radial EBUS cryobiopsy is a feasable alternative in diagnosis of SPN. The yield is comparable to previously reported techniques, however the larger specimens obtained by cryobiopsy could potentially provide invaluable data in malignant conditions. Introduction/Aim: Histolopathology is often required to achieve a multidisciplinary diagnosis in diffuse parenchymal lung disease. Surgical lung biopsy (SLB) remains the gold standard but is associated with significant morbidity and mortality. Recent emergence of transbronchial cryobiopsy (TBCB) as a potential alternative to SLB, promising less complications and a comparable yield, has divided the world of interventional pulmonology. There have been numerous publications reporting different and occasionally contradicting outcomes. Despite relative popularity of TBCB in our region, so far there have not been any published series from Australia.

University and Liverpool Hospitals in Sydney for diagnosis of diffuse parenchymal lung disease between August 2013 and June 2017 were included. A retrospective audit was undertaken to obtain demographic, baseline physiological and Procedural data. Complications and length of stay were recorded. Diagnostic value of TBCB was assessed by its histopathological and clinical impact. All biopsy specimens were reviewed by a single investigator to record size, presence of artefact, percentage of alveolar area and presence of pleura or proximal airway structures.

Results: A total of 46 patients (25 male, average age 62.2) were enrolled in this study. All cases were performed under general anaesthesia with rigid bronchoscope access. An average of 6.1 biopsies were obtained from 1-3 lobes. Most patients were discharged home the same day (65.7%) with average length of stay of 1.05 nights. Pneumothorax was observed in 10.5% of the patients with severe endobronchial bleeding in 5.2%. There were no deaths reported within 30 days of the procedure. Histopathological data as well as yield are currently being analysed.

Conclusion: Our preliminary data suggests that TBCB is a relatively safe procedure with an acceptable yield which could be considered as an alternative to SLB. Grant Support:

Editorial material and organization © 2018 Asian Pacific Society of Respirology. Copyright of individual abstracts remains with the authors. Introduction/Aim: Emphysema is a leading cause of disability and death. Its current medical treatment shows certain limitations in the advanced stage of the disease. Also, there is limited evidence in the Australian setting regarding therapeutic interventions for reducing hyperinflation, including endobronchial valves insertion (EBV). This study examined the outcomes of EBV insertion in patients with severe emphysema at the Royal Brisbane and Women's Hospital.

Methods: This is a retrospective review of patients with severe emphysema who underwent EBV insertion from 2011-2017. The primary outcomes were change in exercise tolerance as measured by the sixminute walk test (6MWT) and quality of life (QoL) as measured by the St. George's Respiratory Questionnaire (SGRQ) and direct questioning.

Variables of interest were measured pre-and post-EBV placement.

Results: Of the 31 patients included in the study, 15 were females.

Age ranged from 50 to 80 years (median age=67 years). Sixteen patients had no complications, and 9 patients had multiple complications. Three patients were readmitted within 30 days and 2 died mainly due to old-age co-morbidities. Ninety-day mortality rate was 0%. Pre and post values for 6MWT were obtained for 18 patients, SGRQ for 10 patients, and QoL data for 24 patients. Patients with complete data (25) showed improved mean values of SGRQ, 6MWT, and lung function. Mean SGRQ was reduced by 24 units (p=0.001), and 6MWT was increased by 78 metres (p=0.001). Mean FEV1 was increased by 4% (p=0.006), and residual volume and TLC were reduced by 25% and 11% (p=0.009 and 0.01), respectively. Significant improvement in QoL was reported in 13 patients while 11 reported improvement/slight improvement.

Conclusion: EBV is an effective and safe therapy that improves lung function, exercise capacity, and QoL in selected patients with emphysema. Further studies on a larger population need to confirm our findings. 

Introduction/Aim: In randomized controlled trials, bronchial thermoplasty (BT) has been proven to reduce symptoms in severe asthma. The mechanisms by which this is achieved are still uncertain as no improvement in spirometry is observed in most studies. We postulated that BT might improve lung mechanics by altering airway resistance in the small airways of the lung in ways not measured by FEV1. This study aimed to evaluate changes in measures of gas trapping particularly the Residual Volume (RV).

Methods: A prospective cohort of 32 consecutive patients with severe asthma who were listed for BT at two tertiary institutions (Frankston Hospital and Macquarie University Hospital) were evaluated at three time points, namely baseline, and then 6 weeks and 6 months post completion of all procedures. At each evaluation, medication usage, symptom scores (Asthma Control Questionnaire, ACQ-5) and exacerbation history were obtained, and lung function was evaluated by (i) spirometry (ii) gas diffusion (DLCO) and (iii) static lung volumes by body plethysmography.

Results: ACQ-5 improved from 3.0AE0.8 at baseline to 1.5AE0.9 at 6 months (meanAESD, p<0.001). Daily reliever salbutamol usage improved from 8.3AE5.6 to 3.5AE4.3 puffs per day (p<0.001). Exacerbation frequency and maintenance oral corticosteroid usage also significantly declined (p<0.001), but no changes in any spirometric parameter were demonstrated. DLCO was also unaltered by BT treatment. However, a significant reduction in gas trapping was observed with RV falling from 146AE37% predicted to 136AE29%predicted (p,0.002, paired t test). Significant improvements in TLC and FRC were also observed. These changes were evident at the 6 week time period and maintained at 6 months. The change in RV was negatively correlated with the baseline FEV1, r=-0.474, p=0.006, indicating that the greatest improvement was evident in the most obstructed patients.

: Bronchial thermoplasty appears to improve gas trapping and this effect is greatest in the most severely obstructed patients. The improvement may relate to changes in the mechanical properties of small airways that are not measured with spirometry. Introduction/Aim: COPD and smoking play a vital role in development of NSCLC. Local progression and metastasis of NSCLC has been associated with epithelial mesenchymal transition (EMT), which is implicated in COPD pathogenesis.

We have investigated EMT biomarkers (S100A4, Vimentin, and N-cadherin), an epithelial activation marker (EGFR) and a vascularity marker (Type-IV collagen) in surgically resected tissue from patients with NSCLC (adeno-and squamous cell carcinoma), and compared them with corresponding non-tumorous airways.

Results: EGFR, S100A4, vimentin, N-cadherin expression was higher in tumour cells, at the peripheral leading edge of NSCLC when compared with centrally located tumour cells of same subjects (P<0.01). Same was with Type-IV collagen expressing blood vessels. EGFR and S100A4 expression was related to differentiation status (P<0.05) and TNM stage (P<0.05) of NSCLC. Moreover, EMT markers in the leading edge were significantly related to airway EMT activity, while peripheral edge vascularity of squamous cell-carcinoma only was significantly related to large airway Rbm vascularity (P<0.05).

Conclusion: EGFR and EMT-related protein expression was remarkably high at peripheral leading edge of NSCLCs and related to tumour characteristics associated with poor prognosis. The relationships between EMT-related tumour bio-marker expression and those in the airway epithelium and Rbm, provides a background for utility of airway changes in clinical settings. Methods: QLCSS screened 256 healthy volunteers aged 60-74 with extensive current or former smoking history (pack years ≥30, quit <15 years prior). Scan results were defined based on 12 months follow-up: falsepositive scans (FP) were lung cancer-free at 1 year; true-positives (TP) were not. There were no false negatives. Global health status (physical and mental function) was assessed using a 4-week recall period at baseline (pre-screening), 1 month, 6 months and 12 months after baseline screening scan using the Short Form 12 version 2.0 (SF-12). SF-12 contains twelve questions. Aggregate summary measures (Mental Component Summary (MCS) and Physical Component Summary (PCS)) were calculated using factor weights derived from a 1998 US general population sample. MCS and PCS range between 0 and 100; higher values indicate better health. The Minimally Important Difference determined clinically meaningful differences (MID = half of a standard deviation (SD) of the mean).

Results: Response to each questionnaire was ≥88% (table 1) . Baseline mean (SD) for MCS and PCS were 54.82 (6.83) and 49.90 (7.72) respectively. MCS was above or at the general population norm in 91%; PCS was above or at the norm in 76%. Small changes, below MID, were seen in FP and Negative groups at most time-points ( Figure 1 ). Larger changes were seen in TP group, however, the number of responses was very small.

Conclusion: Screening was associated with small measurable changes in global HRQoL. There was no clinically meaningful difference between participants with negative or FP scans.

Grant Support: NHMRC, Queensland Government Smart State grant, The Prince Charles Hospital Foundation.

Mean change in Physical Component Score and Mental Component Score from baseline. Introduction/Aim: Exercise training delivers significant short-term improvements in functional exercise capacity, symptoms and quality of life, across the range of interstitial lung diseases (ILD)s, but to what extent do individuals experience a clinically significant benefit? This study aimed to establish the proportion of patients achieving the minimal important difference (MID) in 6-minute walk distance (6MWD) and in the dyspnoea and fatigue domains of chronic respiratory questionnaire (CRQ).

Methods: Data from 142 participants with ILD [61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with ILD of other aetiologies] randomised to either eight weeks of supervised exercise training or usual care were reviewed. We compared the percentages of patients who achieved the MID for 6MWD for ILD (29-34m), CRQ dyspnoea (2.5 points) and CRQ fatigue (2.0 points) between exercise training and control group for the entire ILD population and each subgroup (IPF, asbestosis and CTD-ILD) using Pearson chi 2 .

Results: Following exercise training at least a third of participants achieved improvements in 6MWD that exceeded the MID, increasing to 43% and 55% in the IPF and asbestosis subgroups respectively (see Table) . Compared to the control group, a greater percentage of participants achieved improvements that exceeded the MID for CRQ dyspnoea and fatigue for the entire ILD sample, IPF and asbestosis; this was significantly greater than the control group for CRQ fatigue. Improvements that exceed the MID were limited in CTD-ILD and more likely occur in CRQ dyspnoea and fatigue than 6MWD.

Conclusion: A third to a half of participants with ILD achieve clinically meaningful improvement following exercise training, including those with IPF, the most devastating of all ILDs. Fatigue and 6MWD appear more responsive to change than dyspnoea. Grant Support: This abstract is funded by the ATS Foundation/Pulmonary Fibrosis Foundation, National Health and Medical Research Council, Eirene Lucas Foundation and Institute of Breathing and Sleep. p <0.05 compared to control group; ILD, interstitial lung disease; CTD ILD, connective tissue disease-related ILD; IPF, idiopathic pulmonary fibrosis.

Editorial material and organization © 2018 Asian Pacific Society of Respirology. Copyright of individual abstracts remains with the authors.

In pooled data from the TOMORROW and INPULSIS ® trials, the incidence of major adverse CV events was similar between nintedanib and placebo groups both in patients with higher and lower CV risk at baseline. Grant Support: The study was funded by Boehringer Ingelheim.

Declaration of interest statement: TC has received unrestricted educational grants, travel assistance and served on an advisory board for Boehringer Ingelheim and Roche Products Ltd. She has received unrestricted educational grants from Intermune pharmaceuticals and has served on an advisory board for Astra Zeneca. IN has received institutional grants from Centacor, Immuneworks, Actelion and the National Institutes of Health for conduct of clinical trials in IPF; he is supported by the National Institutes of Health, National Heart, Lung and Blood Institute. MW has received speaker and advisory board fees, paid to her institution, from InterMune, Boehringer Ingelheim and Roche, and unrestricted research grant, paid to her institution from InterMune and Roche. MK has received grants and personal fees from Roche, Boehringer Ingelheim, GSK, Gilead, Prometic and Alkermes; grants from Actelion, Respivert and Synairgen; and personal fees from AstraZeneca and Genoa. FB has received grants and honoraria from Roche/Genentech, InterMune, Boehringer Ingelheim, Serendex and Sekisui Diagnostics. LM and DW are employees at Boehringer Ingelheim. 

Conclusion: A range of interventions, particularly those involving physical activity counselling, can improve physical activity as measured by daily steps. These results suggest that targeted interventions may be useful to improve physical activity in people with COPD. 

Blood glucose and serum insulin levels in children with cystic fibrosis

Cystic Fibrosis-Related Diabetes: Current Trends in Prevalence, Incidence, and Mortality. Diabetes Care

Methods: We report on a further analysis of a prospective randomised patient group. Patients undergoing therapeutic and diagnostic procedures within the RBWH were considered for trial entry and randomization. Procedures included standard bronchoscopy, endobronchial ultrasound (EBUS) with transbronchial node aspiration (TBNA) or EBUS Guide Sheath. Patients were randomized to either CS or GA, stratified for Charlson Comorbidity Index. GA was defined as the use of a Laryngeal mask airway and/or propofol usage. Diagnosis obtained at bronchoscopy was compared to the final clinical diagnosis. Results: 93 patients were randomised. 49 of these received CS of which 32 were diagnostic procedures, with 14 being EBUS TBNAs. In the GA group these numbers were 44, 32 and 14 respectively. A final diagnosis of malignancy was made in 12 cases in the CS group (38%) and 18 cases in the GA group (56%). For all diagnostic procedures there was no significant difference in diagnostic accuracy between CS and GA, 93.3 vs 87.5% (p=0.67). Regarding EBUS TBNA diagnostic accuracy was 100 vs 92.9% (P=1.00). 24 lymph nodes were sampled in the CS group, 46% paratracheal, 17% subcarinal and 38% hilar. 21 nodes were sampled in the GA group, 24% paratracheal, 29% subcarinal and 48% hilar

Conclusion: CS is not inferior to GA in terms of diagnostic accuracy, including EBUS TBNA from a wide range of nodal stations

At our tertiary institution, we routinely perform cryobiopsy with general anaesthesia, endotracheal intubation and fluoroscopy guided 1.9mm cryoprobe via ERBECRYO 2 with routine bronchial blocker balloon deployment. We thus set out to establish the safety and usage patterns of our cryobiopsy service. Methods: Following institutional ethics approval, we conducted a retrospective audit of our institution's cryobiopsy register

Same day discharge was achieved in 42/49, with 2 further uncomplicated cases staying overnight for social reasons. There were no cases of severe bleeding. Bleeding was moderate (controllable with endobronchial interventions) in 5 cases; 4 cases had pneumothoraces of whom 2 required intercostal catheter insertion. Physicians agreed or strongly agreed that cryobiopsy was helpful in 45/49 patients

Methods: Pleural fluid was prospectively collected from 110 consecutive pleural effusion cases. The fluid was analysed by an accredited laboratory (PathWest, WA) for protein, lactate dehydrogenase (LDH), cholesterol and triglycerides. Aetiology of the effusion was independently verified based on clinical, radiological and pathological assessment. The effusion was classed as an exudate (89) or transudate (21) based on final aetiology. Results: Exudates were mainly due to malignancy (68 including 13 lung, 6 breast, and 26 mesothelioma effusions), pleural infections (6) and benign pleuritis (5)

Exudates were identified with a high discrimination (accuracy 95.5%, sensitivity 96.7% and specificity 90.5%) when fluid protein (>35), LDH (>225) and cholesterol (>1.5) with modified cut-offs were combined. Conclusion: Pleural fluid cholesterol and triglyceride levels are higher in exudates

A combined fluid protein, LDH and cholesterol criteria is useful in distinguishing exudates from transudates. Grant Support: NHMRC; Cancer Council WA (RT, YCGL, JC); Cancer Australia

Sir Charles Gairdner Research Advisory Group (YCGL)

Australia Introduction/Aim: To investigate the feasibility and efficacy of exercise to improve physical functioning, body composition, and patient

Outcomes assessed at baseline and post-intervention included muscular strength (1-repetition maximum leg press), functional capacity (6-Minute Walk Test), physical functioning (Timed Up and Go), body composition (DXA scan), quality of life (Short-Form 36 Health Survey), ratings of intervention burden and acceptability (7-point Likert scale; 1, not at all, to 7, very much). Paired T-test or Wilcoxon Signed Rank Test was used to assess changes over time. Results: Mean participant age was 64 (SD =11) years. The majority had mesothelioma (93%), ECOG performance status 0-1 (97%), and were male (70%), and sarcopenic (56%). Twenty-six participants (79%) completed the intervention; 24 (73%) completed all post-intervention assessments. Median adherence to supervised exercise was 100% (range 6%-100%). Median ratings of trial evaluation were high

95% CI 24-93; p<0.05), 1-repetition maximum leg press

95% CI 11-23; p<0.001), timed up and go (-0.51 sec

and appendicular lean mass/height squared (+0.19 kg/m 2 ; 95% CI 0.04 -0.34; p<0.05). For patient-rated outcomes, only the mental health subscale of SF-36 changed significantly

This study aims to improve the diagnostic value of EBUS bronchial brushings by screening these specimens for molecular changes that can identify therapeutic targets. More specifically, to assess the feasibility of using EBUS bronchial brushings to detect differentially expressed tumour markers using Taqman Low Density Array (TLDA) RT-qPCR. Methods: Single pass radial EBUS brushings from Non-Small Cell Lung Cancer (NSCLC) patients (n=15) were collected following ROSE confirmation of the malignant site at the Royal Melbourne Hospital. Final diagnoses included adenocarcinoma (n=10) and squamous cell carcinoma (SCC, n=5)

According to tumour type a fold increase in PD-L1 (8.50AE2.26, p<0.02), RICTOR (1.84AE0.28, p<0.003) and MET (3.51AE1.38, p<0.005) were observed in adenocarcinomas vs. SCCs. FGFR1 levels were higher (6.86AE4.5 fold, p<0.02) and PTEN levels were lower (0.64AE0.12 fold, p<0.001) in SCCs vs. adenocarcinomas. The malignant nature of the lesions were confirmed by NGS, identifying common mutations in p53

451 placebo) had higher CV risk and 124 (10.1%) patients (67 nintedanib, 57 placebo) had lower CV risk. In patients with higher CV risk, incidence rates (95% CI) of MACE were 3.88 (2.58, 5.84) and 3.49 (2.10, 5.79) per 100 -patient-years in the nintedanib and placebo groups, respectively (Figure). In patients with lower CV risk

GLASPOLE I 3 , GLASSBERG M 4

UK Introduction/Aim: Declines in forced vital capacity (FVC), declines in 6-min walk distance (6MWD) and respiratory hospitalizations are events associated with disease progression and mortality in IPF. The incidence of multiple events in the context of a 52-week study and in patients (pts) receiving antifibrotic treatment with pirfenidone (PFD) is unknown. To determine the incidence of multiple progression events and the proportion of pts with death subsequent to a progression

PFD n = 623; PBO %predicted FVC ≥10%, absolute decline in 6MWD ≥50 m; respiratory hospitalization, or death from any cause. Results: The incidence of progression events was driven by declines in FVC (total events, 202 PFD vs 304 PBO) and 6MWD (265 PFD vs 348 PBO). A lower proportion of pts had > 1 event with PFD vs PBO

Death following ≥ 1 progression event occurred less often with PFD vs PBO (2.1% vs 6.3%

Conclusion: PFD significantly reduced the incidence of multiple pro

INTERVENTIONS FOR PROMOTING PHYSICAL ACTIVITY IN PEOPLE WITH COPD: A COCHRANE SYSTEMATIC REVIEW

Australia Introduction/Aim: Increasing awareness of the deleterious health impacts of physical inactivity in people with chronic obstructive pulmonary disease (COPD), coupled with technological developments permitting more accurate measurements, has led to a dramatic increase in studies that aim to improve physical activity participation. This systematic review aimed to evaluate the effectiveness of interventions to promote physical activity in people with COPD. Methods: Randomised controlled trials of interventions designed to increase physical activity for people with COPD using objective measures for

Two review authors independently assessed studies for inclusion and risk of bias, then undertook data extraction. Results are for the primary outcome of steps/day at program completion, using published data. Results: 1950 references were screened, 189 papers assessed and 32 of 72 included studies reported steps/day. The greatest improvements were seen with physical activity counselling and a pedometer

Significant improvements were also demonstrated with telephone counselling and a pedometer (compared to pedometer alone, 1 study, 1419 [698 to 2140] steps/day) and endobronchial valves (compared to usual care, 1 study, 1400 [655 to 2145] steps/ day]). A deterioration in step count was seen following singing classes (compared to film workshops, 1 study, -1774 [-2848 to -700] steps/day). Risk of selection and detection bias was generally low

Acknowledgements: WCH Foundation, NHMRC Project Grant APP1079712, and www.cure4cf.org. Australian Synchrotron proposal number AS162/IMBL/10788.

Introduction/Aim: Comparative physiology is a powerful approach to help understand the relationship between structure and function. The kangaroo exhibits a unique breathing mechanism when hopping: respiration depends more on motional forces and less on active contraction of the diaphragm. We asked how structural and mechanical properties of the kangaroo airway might accommodate the respiratory pressures generated during hopping. This study compared mechanical and structural properties of airways from kangaroos and sheep, the latter of which is not subject to the same motion-driven movement of air.Methods: Bronchial segments from kangaroos (n=8) and sheep (n=12) were mounted in an organ bath chamber. Pressure-volume curves were obtained between -10 and 20 cmH 2 O before and after theophylline. Airway stiffness was calculated from the change in pressure over normalized volume (Δ volume/initial volume). Closing pressure (pressure required for airway collapse) and airway wall morphology were also assessed. Data is meanAESEM.Results: The stiffness of kangaroo airways was less than in sheep (kangaroo, 6AE2 cmH 2 O; sheep, 16AE4 cmH 2 O; p<0.05). Theophylline caused a reduction in sheep airway stiffness (p<0.05) but had no effect on kangaroo airway stiffness, suggesting a role for smooth muscle tone in the former. Kangaroo airways also required a less negative pressure for collapse compared with sheep airways (kangaroo, -15AE3 cmH 2 O; sheep, -30AE3 cmH 2 O; p<0.05).The kangaroo airway had a thicker inner (p<0.05) and thinner outer wall (p<0.05) compared with the sheep airway. While the total thickness of cartilage was comparable between groups, there were a greater number (p<0.05) of smaller (p<0.05) cartilage plates in the kangaroo airway. migration and repair. Therefore, it was hypothesised that aberrant Notch signalling in asthmatic epithelium would result in defective repair by airway epithelial cells(AEC) via regulation of integrins.Methods: Tracheobronchial airway brushings of non-asthmatic (n=18; age range: 1.2-15.6yr; 8 males) and asthmatic (n=14; 3.3-16.9yr; 12 males) children were utilised for AEC isolation and culture. Notch receptor and ligand gene expression was investigated by qPCR (mean-AESEM; arbitrary units, AU). Notch signalling in cultures was inhibited with gamma secretase inhibitor, DAPT(N-[N-(3,5-Difluoro-phenacetyl)-L-alanyl]-S-phenylglycine-t-butyl ester) over a dose-range (1nM-10μM). Linear wounds were performed on AEC to assess repair (IncuCyte ZOOM ® , Essen Bioscience). Integrin α5β1 protein expression was investigated by In-Cell™ Western.Results: Notch receptors (NOTCH1-4) and ligands (JAG1-2, DLL1, 3, 4) were found to be expressed in ex vivo AEC from non-asthmatic and asthmatic children, however only NOTCH2 and JAG1 gene expression were differentially expressed in AEC from asthmatic children (NOTCH2, 10-fold downregulation[p<0.01]; JAG1, 3.5-fold upregulation[p<0.01]; n=6). Following in vitro wounding, NOTCH2 (2.92AE0.11AU) and JAG1(3.35AE0.14AU) mRNA levels were induced within 48hr in AEC of nonasthmatic children. However, an earlier induction of both NOTCH2 (2.58AE0.10 AU) and JAG1 (4.19AE0.09 AU) at 24hr post wounding was observed in AEC from asthmatic children. Global inhibition of Notch signalling resulted in a 40% reduction in wound repair and an inability to close the wound, observed at the maximal dose, 10μM. Furthermore, Notch signalling inhibition resulted in a reduction of α5 integrin protein expression of 30% at 500 nM DAPT, but not β1 integrin protein Conflict of Interest: All authors declare no conflict of interests. Conclusion: These findings demonstrate that targeted RT-qPCR profiling can identify molecular abnormalities in EBUS bronchoscopy brushings collected from ROSE confirmed malignant lesions. Further investigation is warranted as to whether RT-qPCR can be used clinically to guide individualised therapeutic options. Methods: Consecutive series of patients who received nivolumab for advanced NSCLC on an intention-to-treat basis over a 30 months period between January 2015 and June 2017 at a large thoracic-oncology unit were identified. Outcomes in patients who had received radiation therapy to the chest as part of previous treatment prior to commencing nivolumab (RT group, n=20) were compared to an age, gender, tumour histology and performance status matched cohort of patients who did not receive previous radiation therapy (non-RT group, n=20).Results: The RT group had received a mean 53.3Gy (SD 12 .3) at a median of 12.4 months prior to commencing nivolumab. The median progression free survival (PFS) was 3.4 months (95%CI 2.2-4.5) in the RT group compared to 1.3 months (95%CI 1.0-1.7) in the non-RT group (p=0.01). The median overall survival was 8.4 months (95%CI 5. 1-11.6) in the RT group compared to 4.2 months (95%CI 1.0-7.7) in the non-RT group (p=0.08). The disease response on the initial assessment following starting nivolumab included nine (45%) patients who had stable disease or partial response in the RT group compared to five (25%) in the non-RT group after a median of four cycles of therapy. Rate of immune related complications were 35% (n=7) and 15% (n=3) in the RT and non-RT groups respectively (p=0.1). The RT group had a higher mean smoking pack years.Conclusion: This study demonstrates a novel finding of previous radiation therapy to the chest resulting in significantly higher PFS in patients treated with nivolumab for advanced NSCLC. A trend towards a higher rate of immune related adverse effects seen in the RT group may due to increased activity of the immunotherapy in these patients. 

Declaration of interest statement: NG has received speaker fees from Boehringer Ingelheim, AstraZeneca, Menarini and Novartis and consultation fees from Boehringer Ingelheim and Roche. BC has received grants, personal fees and non-financial support from Roche/InterMune and Boehringer Ingelheim; personal fees and non-financial support from Sanofi; grants from Cardif, LVL and MedImmune, and personal fees from AstraZeneca. MK has received grants and personal fees from Roche, Boehringer Ingelheim, GlaxoSmithKline, Gilead, Prometic and Alkermes; grants from Actelion, Respivert and Synairgen; and personal fees from AstraZeneca and Genoa.BW has nothing to disclose. MQ and WS are employees of Boehringer Ingelheim. LR served on the scientific advisory boards of InterMune, Boehringer Ingelheim, FibroGen, GlaxoSmithKline, Sanofi-Aventis, Anthera, Genentech, MedImmune, Takeda, UCB, and Promedior and as a trial Principal Investigator for Boehringer Ingelheim, InterMune, Gilead, Roche, Takeda, and UCB; received research grants from InterMune, Biogen, Italian Ministry of Health, Italian National Drug Agency, and Wellcome Trust and speaker's fees from InterMune, Boehringer Ingelheim and Cipla. Department of Radiology, Mayo Clinic, Rochester, USA Introduction/Aim: Idiopathic pulmonary fibrosis (IPF) is the most aggressive and frequent form of idiopathic interstitial pneumonias. Progression of IPF is variable between individuals and no established quantitative tools exist to assess its development. This work aims to integrate information from volumetric imaging with pulmonary function tests using a predictive computational model under the hypothesis that abnormalities on volumetric are not sufficient to explain increased lung stiffness and decreases in DLCO.Methods: Tissue regions in HRCT images from 8 patients with IPF were quantitatively analysed. Tissue abnormalities were classified using CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings) software. Tissue density (TD) distribution and volume of tissue (classified as reticular, ground-glass, normal and emphysema in each lung) were calculated. The classified data were mapped to a statistical shape model, which allows consistent comparison of regional tissue properties between patients or within one patient at different time points. Ventilation distribution and gas exchange were simulated in a computational model that was parameterised to each subject's lung tissue characterisation, to predict the relationship between V-Q matching, DLCO and disease distribution.Results: Fibrosis usually has a consistently higher TD (0.34/0.41 for reticular/ground-glass) compared to normal tissue (0.28), and presents predominantly in lower lobes (72%, 58%, 65% for honeycomb, reticular, ground-glass). In contrast, emphysema has lower density (0.08) and appears predominantly in upper lobes (73%). Model predictions of ventilation distribution and DLCO show that V-Q mismatch occurs due to redistribution of ventilation away from diseased regions, contributing to observed DLCO decreases.Conclusion: A quantitative analysis of the spatial distribution of IPF disease coupled with functional models provides a potential tool to improve assessment of the contributors to decline in IPF patient status over time. Decline in DLCO is a function of regional lung stiffness due to disease location combined with a redistribution of ventilation to 'normal' lung tissue.Grant Support:Introduction/Aim: Tyrosine kinase inhibitors may be associated with an increased risk of arterial thromboembolic events. The efficacy and safety of treatment with nintedanib versus placebo in patients with idiopathic pulmonary fibrosis were assessed in the Phase II TOMORROW trial and 2 Phase III INPULSIS ® trials. Exclusion criteria included: myocardial infarction in the previous 6 months, unstable angina in the previous month or stroke in the previous year. We assessed the effect of cardiovascular (CV) risk at baseline on the CV safety of nintedanib 150mg twice-daily.Methods: Incidence rates of major adverse CV events (MACE) in subgroups of patients with a history of atherosclerotic CV disease (CVD) and/or ≥1 CV risk factor (hypertension, dyslipidemia, body mass index >30 kg/m 2 , current/former smoking and diabetes) at baseline (higher CV risk) and patients with no history of atherosclerotic CVD and no CV risk factors at baseline (lower CV risk) were analysed using pooled data from the TOMORROW and INPULSIS ® trials. Appropriate requesting of CTPA is important to both establishing an accurate diagnosis and minimizing unnecessary testing and radiation exposure. International and Waikato Hospital guidelines recommend pre-test probability scoring and D-dimer assay to stratify patients prior to performing CTPA.We aimed to determine the overall and departmental diagnostic yield of CTPA at Waikato Hospital. We also aimed to identify whether CTPA were ordered according to current guidelines.Methods: Medical records of 200 consecutive patients who underwent CTPA for suspected PE from 01 March to 31 May 2017 were retrospectively reviewed. Patient demographics, referral source, clinical risk factors, D-dimer levels, diagnostic yield and additional CTPA findings were recorded. We utilized an age-adjusted D-dimer cut-off. CTPA images were obtained using either a Siemens 128 or 256 slice multidetector CT scanner. Results were compared with international guidelines as well as similar local studies.Results: 41 (20.5%) patients had PE. Orthopaedics had the highest yield (36.4%), followed by Respiratory (32.9%) and General Surgery (18.8%). According to the Wells Score, 74 (37%) patients were low risk while 134 (63%) were High Risk. D-dimer was done in 108 (54%) patients. 34 (44.7%) patients in the low-risk group did not have D-dimer. Two patients who had low wells score and negative D-dimer received CTPA, neither had PE. Of the 14 patients referred by cardiology, none had positive scans. On review, only one patient had CTPA requested inappropriately (low wells score, D-dimer not done).Conclusion: Diagnostic yield of CTPA in Waikato Hospital is consistent with international standard. D-dimer has not been adequately used as a rule out test. Adherence to diagnostic protocol could potentially improve positive yield.

No funding or financial support was received from any organization.