Does diet quality moderate the long-term effects of discrete but extreme PM2.5 exposure on respiratory symptoms? A study of the Hazelwood coalmine fire.

In 2014, a fire at an open cut coalmine in regional Victoria, Australia burned for 6 weeks. Residents of the nearby town of Morwell were exposed to smoke, which included high levels of fine particulate matter (PM2.5). We investigated whether the long-term effects of PM2.5 on respiratory health were moderated by diet quality. A cross-sectional analysis was conducted of data collected 8.5 years after the mine fire from 282 residents of Morwell and 166 residents from the nearby unexposed town of Sale. Primary outcomes were respiratory symptoms. Exposure was coalmine fire-related PM2.5 and diet quality was assessed as Australian Recommended Food Score (ARFS) derived using the Australian Eating Survey (AES). The moderating effect of diet quality on respiratory outcomes associated with PM2.5 was assessed using logistic regression models, adjusting for potential confounders. Diet quality was poor in this sample, with 60% in the lowest category of overall diet quality. Overall diet quality and fruit and vegetable quality significantly attenuated the association between PM2.5 and prevalence of chronic cough and phlegm. Sauce/condiment intake was associated with a greater effect of PM2.5 on COPD prevalence. No other moderating effects were significant. The moderating effects of overall diet quality and vegetable and fruit intake aligned with a priori hypotheses, suggesting potential protective benefits. While more evidence is needed to confirm these findings, improving diets, especially fruit and vegetable intake, may provide some protection against the effects of smoke exposure from fire events.

Long-term effects of extreme smoke exposure on COVID-19: A cohort study.

BACKGROUND: In 2014, the Hazelwood coalmine fire shrouded the regional Australian town of Morwell in smoke and ash for 6 weeks. One of the fire's by-products, PM2.5 , is associated with an increased risk of COVID-19 and severe disease. However, it is unclear whether the effect persisted for years after exposure. In this study, we surveyed a cohort established prior to the pandemic to determine whether PM2.5 from the coalmine fire increased long-term vulnerability to COVID-19 and severe disease. METHODS: From August to December 2022, 612 members of the Hazelwood Health Study's adult cohort, established in 2016/17, participated in a follow-up survey that included standardized items to capture COVID-19 cases, as well as questions about hospitalization and vaccinations. Associations were evaluated in crude and adjusted logistic regression models. RESULTS: A total of 268 (44%) participants self-reported or met symptom criteria for having had COVID-19 at least once. All models found a positive association, with odds of COVID-19 increasing by between 4% and 30% for a 10 µg/m3 increase in coalmine fire-related PM2.5 exposure. However, the association was significant in only 2 of the 18 models. There were insufficient hospitalizations to examine severity (n = 7; 1%). CONCLUSION: The findings are inconclusive on the effect of coalmine fire-related PM2.5 exposure on long-term vulnerability to COVID-19. Given the positive association that was robust to modelling variations as well as evidence for a causal mechanism, it would be prudent to treat PM2.5 from fire events as a long-term risk factor until more evidence accumulates.

Association between PM2.5 from a coal mine fire and FeNO concentration 7.5 years later.

BACKGROUND AND AIM: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later. METHODS: Adult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups. RESULTS: A total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM2.5 was 7.2 [13.8] µg/m3. We did not identify evidence of association between coal mine fire PM2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups. CONCLUSION: Despite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels.

Oscillometry in Stable Single and Double Lung Allograft Recipients Transplanted for Interstitial Lung Disease: Results of a Multi-Center Australian Study.

Peak spirometry after single lung transplantation (SLTx) for interstitial lung disease (ILD) is lower than after double lung transplantation (DLTx), however the pathophysiologic mechanisms are unclear. We aim to assess respiratory mechanics in SLTx and DLTx for ILD using oscillometry. Spirometry and oscillometry (tremoflo® C-100) were performed in stable SLTx and DLTx recipients in a multi-center study. Resistance (R5, R5-19) and reactance (X5) were compared between LTx recipient groups, matched by age and gender. A model of respiratory impedance using ILD and DLTx data was performed. In total, 45 stable LTx recipients were recruited (SLTx n = 23, DLTx n = 22; males: 87.0% vs. 77.3%; median age 63.0 vs. 63.0 years). Spirometry was significantly lower after SLTx compared with DLTx: %-predicted mean (SD) FEV1 [70.0 (14.5) vs. 93.5 (26.0)%]; FVC [70.5 (16.8) vs. 90.7 (12.8)%], p < 0.01. R5 and R5-19 were similar between groups (p = 0.94 and p = 0.11, respectively) yet X5 was significantly worse after SLTx: median (IQR) X5 [-1.88 (-2.89 to -1.39) vs. -1.22 (-1.87 to -0.86)] cmH2O.s/L], p < 0.01. R5 and X5 measurements from the model were congruent with measurements in SLTx recipients. The similarities in resistance, yet differences in spirometry and reactance between both transplant groups suggest the important contribution of elastic properties to the pathophysiology. Oscillometry may provide further insight into the physiological changes occurring post-LTx.

Laryngeal hypersensitivity and abnormal cough response during mannitol bronchoprovocation challenge.

BACKGROUND AND OBJECTIVE: Inhalational challenge with dry mannitol powder may potentially induce cough by two mechanisms: airway bronchoconstriction or laryngeal irritation. This prospective observational study investigated laryngeal and bronchial components of cough induced by mannitol challenge. METHODS: We recruited consecutive patients referred for clinical mannitol challenge. The Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) was administered. Throughout testing, coughs were audio-recorded to derive a cough frequency index per time and dose of mannitol. Relationships between cough indices, laryngeal hypersensitivity and bronchial hyperresponsiveness (BHR) were examined. Participants were classified by cough characteristics with k-means cluster analysis. RESULTS: Of 90 patients who underwent challenge, 83 completed both the questionnaire and challenge. Cough frequency was greater in patients with abnormal laryngeal hypersensitivity (p = 0.042), but not in those with BHR. There was a moderate negative correlation between coughs per minute and laryngeal hypersensitivity score (r = -0.315, p = 0.004), with lower LHQ scores being abnormal. Cluster analysis identified an older, female-predominant cluster with higher cough frequency and laryngeal hypersensitivity, and a younger, gender-balanced cluster with lower cough frequency and normal laryngeal sensitivity. CONCLUSION: Cough frequency during mannitol challenge in our cohort reflected laryngeal hypersensitivity rather than BHR. Laryngeal hypersensitivity was more often present among older female patients. With the incorporation of cough indices, mannitol challenge may be useful to test for laryngeal hypersensitivity as well as BHR.

Pulmonary function testing during SARS-CoV-2: An ANZSRS/TSANZ position statement.

The Thoracic Society of Australia and New Zealand (TSANZ) and the Australian and New Zealand Society of Respiratory Science (ANZSRS) commissioned a joint position paper on pulmonary function testing during coronavirus disease 2019 (COVID-19) in July 2021. A working group was formed via an expression of interest to members of both organizations and commenced work in September 2021. A rapid review of the literature was undertaken, with a 'best evidence synthesis' approach taken to answer the research questions formed. This allowed the working group to accept findings of prior relevant reviews or societal document where appropriate. The advice provided is for providers of pulmonary function tests across all settings. The advice is intended to supplement local infection prevention and state, territory or national directives. The working group's key messages reflect a precautionary approach to protect the safety of both healthcare workers (HCWs) and patients in a rapidly changing environment. The decision on strategies employed may vary depending on local transmission and practice environment. The advice is likely to require review as evidence grows and the COVID-19 pandemic evolves. While this position statement was contextualized specifically to the COVID-19 pandemic, the working group strongly advocates that any changes to clinical/laboratory practice, made in the interest of optimizing the safety and well-being of HCWs and patients involved in pulmonary function testing, are carefully considered in light of their potential for ongoing use to reduce transmission of other droplet and/or aerosol borne diseases.

Assessing spirometry competence through certification in community-based healthcare settings in Australia and New Zealand: A position paper of the Australian and New Zealand Society of Respiratory Science.

Spirometry has been established as an essential test for diagnosing and monitoring respiratory disease, particularly asthma and COPD, as well as in occupational health surveillance. In Australia and New Zealand, there is currently no pathway for spirometry operators in community-based healthcare settings to demonstrate spirometry competence. The Australia and New Zealand Society of Respiratory Science (ANZSRS) has identified a need for developing a pathway for operators working in community-based practices in Australia and New Zealand to demonstrate spirometry competence and certification. Spirometry certification provides evidence to patients, clients, employers and organizations that an individual has participated in an assessment process that qualifies them to perform spirometry to current international spirometry standards set out by the American Thoracic Society and the European Respiratory Society (ATS/ERS). This document describes a competence assessment pathway that incorporates a portfolio and practical assessment. The completion of this pathway and the award of certification confer an individual is competent to perform spirometry for 3 years, after which re-certification is required. The adoption of this competency assessment and certification process by specialist organizations, and the commitment of operators performing spirometry to undergo this process, will enhance spirometry quality and practice in community-based healthcare settings.

Are e-cigarette use and vaping associated with increased respiratory symptoms and poorer lung function in a population exposed to smoke from a coal mine fire?

BACKGROUND AND OBJECTIVE: E-cigarette use has become increasingly prevalent, but there is some evidence demonstrating potential harms with frequent use. We aimed to identify the profiles of e-cigarette users from a regional community in Australia and investigate the associations of e-cigarettes with respiratory symptoms and lung function. METHODS: A total of 519 participants completed a cross-sectional study. Exposure to e-cigarettes was collected via a validated questionnaire. Respiratory symptoms were evaluated via a self-reported questionnaire and lung function measured with spirometry and forced oscillation technique (FOT). Linear and logistic regression models were fitted to investigate the associations between e-cigarettes and outcomes, while controlling for confounders such as tobacco smoking. RESULTS: Of the 519 participants, 46 (9%) reported e-cigarette use. Users tended to be younger (mean ± SD 45.2 ± 14.5 vs. 55.3 ± 16.0 years in non-users), concurrently using tobacco products (63% vs. 12% in non-users), have a mental health diagnosis (67% vs. 37% in non-users) and have self-reported asthma (63% vs. 42% in non-users). After controlling for known confounders, chest tightness (OR = 2.4, 95% CI 1.2-4.9, p = 0.02) was associated with e-cigarette use. Spirometry was not different after adjustment for confounding. However, FOT showed more negative reactance and a greater area under the reactance curve in e-cigarette users than non-users. CONCLUSION: E-cigarette use was associated with increased asthma symptoms and abnormal lung mechanics in our sample, supporting a potential health risk posed by these products. Vulnerable populations such as young adults and those with mental health conditions have higher usage, while there is high concurrent tobacco smoking.

Long-term impact of coal mine fire smoke on lung mechanics in exposed adults.

BACKGROUND AND OBJECTIVE: In 2014, a 6-week-long fire at the Hazelwood coal mine exposed residents in the adjacent town of Morwell to high concentrations of fine particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5 ). The long-term health consequences are being evaluated as part of the Hazelwood Health Study. METHODS: Approximately 3.5-4 years after the mine fire, adults from Morwell (n = 346) and the comparison town Sale (n = 173) participated in the longitudinal Respiratory Stream of the Study. Individual PM2.5 exposure was retrospectively modelled. Lung mechanics were assessed using the forced oscillation technique (FOT), utilizing pressure waves to measure respiratory system resistance (Rrs) and reactance (Xrs). Multivariate linear regression was used to evaluate associations between PM2.5 and transformed Rrs at 5 Hz, area under the reactance curve (AX5) and Xrs at 5 Hz controlling for key confounders. RESULTS: There were clear dose-response relationships between increasing mine fire PM2.5 and worsening lung mechanics, including a reduction in post-bronchodilator (BD) Xrs5 and an increase in AX5. A 10 µg/m3 increase in mine fire-related PM2.5 was associated with a 0.015 (95% CI: 0.004, 0.027) reduction in exponential (Xrs5) post-BD, which was comparable to 4.7 years of ageing. Similarly, the effect of exposure was associated with a 0.072 (0.005, 0.138) increase in natural log (lnAX5) post-BD, equivalent to 3.9 years of ageing. CONCLUSION: This is the first study using FOT in adults evaluating long-term respiratory outcomes after medium-term ambient PM2.5 exposure to coal mine fire smoke. These results should inform public health policies and planning for future events.

Substantial variation exists in spirometry interpretation practices for airflow obstruction in accredited lung function laboratories across Australia and New Zealand.

BACKGROUND: Spirometry forms the foundation investigation for the diagnosis and monitoring of common pulmonary conditions. However, potential variation in spirometry interpretation for airflow obstruction may impact subsequent clinical management. AIM: To audit spirometry interpretation practices for airflow obstruction in Thoracic Society of Australia and New Zealand accredited laboratories. METHODS: Thirty-nine accredited complex lung function laboratories were invited to participate in an online survey. The survey enquired about demographics, definition of lower limit of normal range for spirometry parameters, spirometric parameters used for identifying airflow obstruction, spirometric definition of airflow obstruction, definition of significant bronchodilator response and chosen spirometry reference equations. RESULTS: Thirty-six laboratories provided complete responses (response rate, 92%). To define the lower limit of normal, 26 of 36 used the 5th percentile, 7 of 36 used a fixed cut-off and 3 used other. Twenty-nine laboratories utilised forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) as the sole parameter to identify airflow obstruction, 3 of 36 used FEV1 /FVC and FEF25-75% , and 4 used other. To define airflow obstruction, 25 of 36 laboratories used FEV1 /FVC < 5th percentile, 9 of 36 used a fixed cut-off (FEV1 /FVC < 0.7, 6/36; FEV1 /FVC < 0.8, 2/36; FEV1 /FVC < 0.75, 1/36) and 2 of 36 used other. Twenty-six laboratories defined a significant bronchodilator response as an increase of at least 200 mL and 12% in FEV1 and/or FVC, 9 of 36 used ≥200 mL and ≥ 12% increase in FEV1 only, and 1 used other criteria. Reference equations utilised for interpretation of spirometry data included: Quanjer 2012 Global Lung Initiative (16/36), the third National Health and Nutritional Examination Survey (8/36), European Community of Coal and Steel (8/36) and other (4/36). CONCLUSIONS: Significant heterogeneity in spirometry interpretation for airflow obstruction exists across Australian and New Zealand accredited lung function laboratories. Lack of standardisation may translate into clinically appreciable differences for the diagnosis and management of common respiratory conditions. Ongoing discussion regarding formal standardisation is required.

Spirometry training courses: Content, delivery and assessment - a position statement from the Australian and New Zealand Society of Respiratory Science.

Spirometry training courses are provided by health services and training organizations to enable widespread use of spirometry testing for patient care or for monitoring health. The primary outcome of spirometry training courses should be to enable participants to perform spirometry to international best practice, including testing of subjects, quality assurance and interpretation of results. Where valid results are not achieved or quality assurance programmes identify errors in devices, participants need to be able to adequately manage these issues in accordance with best practice. It is important that potential participants are confident in the integrity of the course they attend and that the course meets their expectations in terms of training. This position statement lists the content that the Australian and New Zealand Society of Respiratory Science (ANZSRS) has identified as required in a spirometry training course to adequately meet the primary outcomes mentioned above. The content requirements outlined in this position statement are based on the current international spirometry standards set out by the American Thoracic Society and European Respiratory Society. Furthermore, recommendations around course delivery for theoretical and practical elements of spirometry testing and post-course assessment are outlined in this statement.

Airway oscillometry parameters in baseline lung allograft dysfunction: Associations from a multicenter study.

BACKGROUND: Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry measures respiratory system mechanics and may provide insight into understanding the mechanisms of BLAD. OBJECTIVES: This study aims to describe and measure the association between airway oscillometry parameters [Reactance (Xrs5, Ax), Resistance (Rrs5, Rrs5-19)] (1) stable LTx recipients, comparing those with normal spirometry and those with BLAD; and (2) in recipients with chronic lung allograft dysfunction (CLAD), comparing those with normal baseline spirometry and those with BLAD. METHODS: A multi-center cross-sectional study was performed including bilateral LTx between January 2020 and June 2021. Participants performed concurrent airway oscillometry and spirometry. Multivariable logistic regression was performed to measure the association between oscillometry parameters and BLAD. RESULTS: A total of 404 LTx recipients performed oscillometry and 253 were included for analysis. Stable allograft function was confirmed in 149 (50.2%) recipients (92 (61.7%) achieving normal spirometry and 57 (38.3%) with BLAD). Among stable LTx recipients, lower Xrs5 Z-Score (aOR 0.50 95% CI 0.37-0.76, p = 0.001) was independently associated with BLAD. CLAD was present in 104 (35.0%) recipients. Among recipients with CLAD, lower Xrs5 Z-Score (aOR 0.73 95% CI 0.56-0.95, p = 0.02) was associated with BLAD. CONCLUSIONS: Oscillometry provides novel physiologic insights into mechanisms of BLAD. The independent association between Xrs5 and BLAD, in both stable recipients and those with CLAD suggests that respiratory mechanics, in particular abnormal elastance, is an important physiologic feature. Further longitudinal studies are needed to understand the trajectory of oscillometry parameters in relation to allograft outcomes.

Different Case Finding Approaches to Optimise COPD Diagnosis: Evidence from the RADICALS Trial.

Aim: Diagnosis of COPD in primary care is hindered by underuse of spirometry. Case finding using validated symptom and health status questionnaires, and simple handheld devices in high-risk populations may improve diagnosis. This study aimed to determine the best combination of measures to optimise COPD diagnosis in the primary care setting. Methods: We recruited 335 current or ex-smokers, including those with an established diagnosis of COPD from general practices. Participants' FEV1 and FEV6 were measured using a handheld spirometry device (COPD-6®). Each completed the COPD assessment test (CAT), a modified Medical Research Council (mMRC) dyspnoea scale, St George's Respiratory Questionnaire (SGRQ) and smoking history questionnaire. From these data we calculated the predictive validity for spirometry-confirmed diagnosis of COPD. Area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for each. Kappa coefficient was used to measure the agreement between the Fixed-Ratio (FR) and Lower Limit of Normal (LLN) spirometric criteria in diagnosing COPD. Results: FEV1/FEV6 <0.70 alone showed significant association (p<0.0001) with COPD diagnosis and good predictive accuracy (AUROC=0.725). However, no further improvement was found after combining SGRQ, CAT and mMRC with FEV1/FEV6. FEV1/FEV6 <0.70 using the COPD-6® handheld device had moderate sensitivity (65.7%) and high PPV (90.1%), high specificity (79.3%) and NPV (44.8%). There was good agreement between FR and LLN definitions (κ=0.70). Conclusion: Handheld micro-spirometers can facilitate case finding of COPD in smokers and ex-smokers attending general practice. The fixed ratio criterion currently recommended by COPD-X guidelines offers the simplest method for diagnosing COPD in Australian primary care.

The measurement of lung volumes using body plethysmography: a comparison of methodologies.

BACKGROUND: The statement of the American Thoracic Society and European Respiratory Society on the measurement of static lung volumes (SLV) suggests a preferred and alternate method for measuring and calculating SLV. OBJECTIVE: To determine if differences in functional residual capacity (FRC), vital capacity (VC), residual volume (RV), and total lung capacity (TLC), obtained using preferred and alternate measurement and calculation methodologies, exist in a clinical setting. METHODS: Patients attending for SLV at a hospital-based laboratory were recruited. Following spirometry, SLV was measured via body plethysmography, using the preferred and alternate methods in random order. Volumes were calculated using the preferred and alternate calculation methods. Subjects were classified according to standard ventilatory function interpretative strategies. Differences of the means between the measurement methods, and calculation methods were assessed. RESULTS: One hundred eight data sets were analyzed. Significant, but small differences (< 150 mL) in the means for VC and TLC, and RV and TLC were found in the normal and restricted groups, respectively. No significant differences in SLV parameters were found in subjects with air-flow obstruction. Twelve of the 108 changed ventilatory function classification between methods, with the alternate method delivering a lower inspiratory capacity and TLC without a change in RV in 66% of this subgroup. Identical results were obtained when data were analyzed using both calculation methods. CONCLUSIONS: Differences in FRC, VC, RV, and TLC obtained using the preferred and alternate measurement methodologies exist in the clinical setting in select classification groups and individuals. Differing calculation methods dependent on measurement method used may be unnecessary.

Adherence to acceptability and repeatability criteria for spirometry in complex lung function laboratories.

BACKGROUND: Few published data exist for adherence rates to spirometry acceptability and repeatability criteria in clinical respiratory laboratories. This study quantified adherence levels in this setting and observed changes in adherence levels as a result of feedback and ongoing training. METHODS: Two tertiary hospital-based, lung function laboratories (L1 and L2) participated. Approximately 100 consecutive, FVC spirometry sessions were reviewed for each year from 2004 to 2008 at L1 and for years 2004 and 2008 at L2. Each spirometric effort and session was interrogated for adherence to the acceptability and repeatability criteria of international spirometry standards of the time. Feedback of audit results and refresher training were provided at L1 throughout the study; in addition, a quality rating scale was implemented in 2006. No formal feedback or follow-up training was provided at L2. RESULTS: We reviewed 707 test sessions over the 5 years. There was no difference in adherence rates to acceptability and repeatability criteria between sites in 2004 (L1 61%, L2 59%, P = .89). There was, however, a significant difference between sites in 2008 (L1 92%, L2 65%, P < .001). No difference was seen at L2 between 2004 and 2008 (P = .26), while L1 experienced a significant increase in adherence levels between 2004 and 2008 (61% to 92% P < .001). CONCLUSIONS: Clinical respiratory laboratories met published spirometry acceptability and repeatability criteria only 60% of the time in the first audit period. This improved with regular review, feedback, and implementation of a rating scale. Auditing of spirometry quality, feedback, and implementation of test rating scales need to be incorporated as an integral component of laboratory quality assurance programs to improve adherence to international acceptability and repeatability criteria.

Spirometry.

Spirometry measures the flow and volume of air entering and leaving the lungs. It is used to assess ventilatory function and differentiates between normality and diseases causing obstructive and possibly restrictive defects.

Putting lung function reference equations into context.

Knowing the limitations of reference equations is essential to minimising errors in diagnosis and clinical management. Choice of reference sets may impact access to treatment options where lung function based eligibility criteria exist. https://bit.ly/2WdOFDj.

Abnormal one-year post-lung transplant spirometry is a significant predictor of increased mortality and chronic lung allograft dysfunction.

BACKGROUND: The prognostic value of evaluating spirometry at a fixed time point using standardized population reference has not previously been evaluated. Our aim was to assess the association between spirometric phenotype at 12 months (Spiro12M), survival and incidence of chronic lung allograft dysfunction (CLAD) in bilateral lung transplant recipients. METHODS: We conducted a retrospective cohort study of bilateral lung transplant recipients transplanted between January 2003 and September 2012. We defined Spiro12M as the mean of the 2 prebronchodilator FEV1 measurements 12-month post-transplant. Normal spirometry was defined as FEV1/FVC ≥0.7 and FEV1≥80% and FVC≥80% predicted population-based values for that recipient. Abnormal spirometry was defined as failure to attain normal function by 12-months. We used a Cox regression model to assess the association between Spiro12M, survival, and CLAD. We used logistic regression to assess potential pretransplant donor and recipient factors associated with abnormal Spiro12M RESULTS: One hundred and eleven (51%) lung transplant recipients normalized their Spiro12M. Normal Spiro12M was associated improved survival (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.41-0.88], p = 0.009. Each 10% decrement in FEV1 increased the risk of death in a stepwise fashion. Additionally, CLAD was reduced in those with normal Spiro12M (HR:0.65, 95%CI:0.46-0.92, p = 0.016). Donor smoking history (OR:2.93, 95% CI:1.21-7.09; p = 0.018) and mechanical ventilation time in hours (OR:1.03, 95% CI:1.004-1.05; p = 0.02) were identified as independent predictors of abnormal Spiro12M. CONCLUSIONS: Abnormal Spiro12M is associated with increased mortality and the development of CLAD. The effect is dose dependent with increased dysfunction corresponding to increased risk. This assessment of phenotype at 12-months can easily be incorporated into standard of care.

Lumacaftor/ivacaftor-associated health stabilisation in adults with severe cystic fibrosis.

INTRODUCTION: Lumacaftor/ivacaftor (LUM/IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with forced expiratory volume in 1 s (FEV1) % pred >40%. We assessed the clinical utility of LUM/IVA in all eligible adult CF patients with FEV1 % pred <40% treated for at least 1 year under a single-centre managed access programme. METHODS: Following clinical optimisation, eligible patients (n=40) with FEV1 % pred <40% were commenced on LUM/IVA and monitored for tolerance and clinical outcomes, including health service utilisation, pulmonary function, weight and body composition. 24 patients reached 1 year of treatment by the time of evaluation. Six patients discontinued due to adverse events (five for increased airways reactivity) and three underwent lung transplantation. RESULTS: In comparison with the year prior to LUM/IVA commencement, significant reductions (median per year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (from 3 to 1.5; p=0.0002), hospitalisation days (from 27 to 17; p=0.0002) and intravenous antibiotic (IVAB) usage days (from 45 to 27; p=0.0007). Mean±sd change in FEV1 % pred was -2.10±1.18% per year in the year prior, with the decline reversed in the year following (+1.45±1.13% per year; p=0.035), although there was significant heterogeneity in individual responses. Mean±sd weight gain at 1 year was 2.5±4.1 kg (p=0.0007), comprising mainly fat mass (mean 2.2 kg). The proportion of patients severely underweight (body mass index <18.5 kg·m-2) decreased from 33% at baseline to 13% at 1 year (p=0.003). CONCLUSION: This real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, IVABs, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.