Objectives: Lung function assessment is key in CF care, but traditional outcome measures (OMs) such as FEV1 may not be sensitive enough in the CFTR modulator era. LCI2.5 from the multiple breath washout (MBW) is a sensitive measure of small airway disease but can be lengthy in advanced lung disease. Emerging OMs include impulse oscillometry (IOS) & electrical impedance tomography (EIT). Here we report results of cross-sectional analysis of relationships between IOS, EIT, MBW & spirometry in adults with CF. Methods: Cross-sectional analysis from baseline measurements of spirometry, MBW, IOS and EIT from stable patients (n = 68, 42male; mean age 41 y (SD 14.2); mean FEV1 64.5%pred (SD 23.94); mean LCI2.5 18.78 (SD 5.34)) during a randomised controlled trial. Pearson correlation coefficients (r), receiver-operator characteristic (ROC) curves and intraclass correlation coefficients (ICC) between two separate test occasions were calculated (table). Results: R5-R20 from IOS showed significant moderate linear correlations with LCI2.5, LCI5, M1M0, M2M0 & Sacin from MBW, & FEV1, FVC and FEF25–75 from spirometry (r = 0.43 to 0.62, p < 0.05). End expiratory lung impedance (ΔEELI), a key measure from EIT, showed negligible correlations with all tests (r = –0.30 to 0.22, p = <0.05 to 0.57). It was not possible to construct ROC curves for ΔEELI & LCI2.5 due to a lack of a known "normal" for ΔEELI and having all LCI2.5 results classified as "abnormal" (<6.9). R5-R20 ROC curves showed some MBW parameters had good ability to distinguish normal & abnormal (>0.1 kPa) R5-R20. FEV1 ROC curves showed some MBW and IOS parameters had good ability to distinguish between normal & abnormal (≤90% predicted) FEV1. Test-retest reproducibility for all OMs was good (ICCs 0.99 to 0.91). Conclusions: Our data indicate that for adults with CF there is significant linear correlation between IOS & indices of spirometry & MBW. This relationship warrants further investigation with larger datasets as IOS offers a less effortful/time-consuming test than spirometry & MBW respectively. EIT did not show any linear relationships with IOS, spirometry or MBW & thus may not be useful in this context. Table(abstract: WS06.01).Pulmonary function parameters (n = 68)R5-R20End Expiratory Lung Impedance (ΔEELI)LCI 2.5FEV1r (p value)ROC AUCr (p value)ROC AUC*Unable to calculate ΔEELI ROC AUC due to lack of accepted "normal" for ΔEELI.r (p value)ROC AUC**Unable to calculate LCI2.5 ROC AUC due to all LCI results being classified as abnormal (<6.9).r (p value)ROC AUCIOS−0.62 (<0.05)0.92R5-R20−0.20 (0.11)−0.50 (<0.05)−−0.57 (<0.05)0.80R5−0.08 (0.50)−0.38 (<0.05)−−0.31 (<0.05)0.62R200.07 (0.57)−0.11 (0.37)−−0.61 (<0.05)0.98X50.18 (0.15)−0.44 (<0.05)−0.67 (<0.05)0.02Ax−0.19 (0.12)−−0.48 (<0.05)−−0.66 (<0.66)0.95Fres−0.15 (0.23)−0.46 (<0.05)−EITAEELI−0.20 (0.11)0.33−0.31 (<0.05)−−0.13 (0.29)0.42Global Impedance (GI)0.18 (0.15)0.670.14 (0.26)−0.21 (0.08)0.64MBWLCI 2.50.50 (<0.05)0.85−0.30 (<0.05)−−0.70 (<0.05)0.94LCI 50.52 (<0.05)0.84−0.29 (<0.05)−−0.71 (<0.05)0.92FRC−0.06 (0.65)0.49−0.10 (0.42)−0.01 (0.94)0.54M1M00.52 (<0.05)0.85−0.29 (<0.05)−−0.70 (<0.05)0.94M2M00.51 (<0.05)0.85−0.29 (<0.05)−−0.65 (<0.05)0.94Sacin0.43 (<0.05)0.69−0.26 (<0.05)−−0.38 (<0.05)0.71Scond0.09 (0.47)0.61−0.10 (0.44)−−0.13 (0.31)0.64SpirometryFEV1−0.62 (<0.05)0.100.21 (0.08)−−0.70 (<0.05)−FVC−0.60 (<0.05)0.170.22 (0.07)−−0.55 (<0.05)−FEF 25–75−0.53 (<0.05)0.130.17 (0.16)−−−0.72 (<0.05)P < 0.05 statistically significant.Key – negligible correlations (r<0.3), moderate correlations (0.3 0.7).* Unable to calculate ΔEELI ROC AUC due to lack of accepted "normal" for ΔEELI.** Unable to calculate LCI2.5 ROC AUC due to all LCI results being classified as abnormal (<6.9). Open table in a new tab P < 0.05 statistically significant. Key – negligible correlations (r<0.3), moderate correlations (0.3 0.7).

Objectives: Current median survival in the UK in 2021 is 51.4 years for females, and 55.3 years for males. We used mediation analysis to further the understanding of the causal pathways leading to this survival disparity. Methods: We used UK CF Registry data up to 2020 to investigate the extent to which the difference in life expectancy between males and females is explained by trajectories in markers of disease progression over the life course. We considered lung health (represented by FEV1%, lung pathogens and other lung health variables), cystic fibrosis related diabetes (CFRD), and BMI z-score as potential mediators. A causal mediation analysis was used, which accommodates longitudinal variables and baseline and time-dependent dependent confounders. The mediated proportion (MP) for a given mediator at a given age is defined as the percentage by which the difference between the sexes in survival probability up to that age would change if the mediator trajectory in females shifted to be similar to males. Results: The data included 6,341 males and 5,771 females (survival probability to age 30, 0.68 for females, 0.76 for males). From preliminary analyses the MPat age 30was 62.9% (95% CI 34.3-223.5%) for lung health, i. e. at age 30, the female survival probability would be 62.9% closer to that of males. For CFRD the MP at age 30 was 11.0% (3.6% - 38.1%). For survival to older ages the MP was smaller for lung health, but larger for CFRD, suggesting a larger mediating role of CFRD at older ages. The MP at age 30 for BMI z-score was negative (-28.3%, 95% CI -(103.4% - 12.4%)) meaning that if females had the same BMI z-score trajectory as males then their survival probability at age 30 would be expected to be 28.3% worse. Conclusions: Several different factors were found to mediate the effect of sex on survival in CF. The most important mediating factor was found to be lung health. Further work will investigate other potential mediators and subcomponents of lung health

BACKGROUND:Understanding the pulmonary impact of changes in early life nutritional status over time in a paediatric CF population may help inform how to use nutritional assessment to guide clinical care. National registry data provides an opportunity to study patterns of weight gain over time at the level of the individual, and thus to gain detailed understanding of the relationship between early weight trajectories and later lung function in children with Cystic Fibrosis (CF). METHODS:Using data from the United Kingdom (UK) and Canadian CF Registries, a mixed effects linear regression model was used to describe children's weight and BMI z-score trajectories from age 1 to 5 years. The intercept (weight-for-age at age 1) and slope (weight-for-age trajectory) from this model were then used as covariates in a linear regression of first lung function measurement at age 6 years. RESULTS:In both the UK and Canadian data, greater weight-for-age z-score at age 1 year and greater change in weight-for-age over time were associated with higher FEV1% predicted. A greater weight-for-age z-score at age 1 year was associated with a higher FEV1% predicted (UK: 3.78% (95% CI: 1.76; 4.70); Canada: 3.20% (95%CI: 1.76, 4.70)). These associations were reproduced for BMI z-scores and FVC% predicted. CONCLUSIONS:Early weight-for-age, specifically at age 1 year, and weight-for-age trajectories across early childhood are associated with later lung function. This relationship persists after adjustment for potential confounders. Current guidelines may need to be updated to place less emphasis on a specific cut-off (such as the 10th percentile) and encourage tracking of weight-for-age over time.

ivacaftor, or triple-combination therapy (TCT) with elexacaftor/tezacaftor/ ivacaftor were also recorded prospectively.Results: In clinical practice, the CF-ABLE score performed substantially better than it did in its original derivation study and outperformed FEV 1 alone as a predictor of outcome.A CF-ABLE score of 5 or greater clearly distinguished PwCF who went on to poor outcomes from those who did not ( p < 0.001).Approximately half of PwCF with a score of 5 or greater died or underwent lung transplantation within 4 years.In contrast, poor outcome at 4 years was observed in fewer than 5% of PwCF with a score less than 5.The score correlated with sputum neutrophil elastase activity; matrix metalloprotease activity; and interleukin (IL)-1β, IL-6, and IL-8 levels and inversely with IL-10 (all p < 0.05).For each mediator, the correlation with CF-ABLE score was stronger than with FEV 1 alone (all p < 0.05).In F508del/ F508del PwCF, DCT did not result in better FEV 1 at 24 months than in matched controls not receiving DCT but significantly improved CF-ABLE score ( p = 0.002), largely because of an effect on exacerbations.In contrast, TCT resulted in marked decreases in CF-ABLE score within 3 months ( p < 0.001), enabling PwCF with baseline scores of 5 or greater to return to the low-risk range.Conclusions: The CF-ABLE score robustly identifies PwCF at risk of poor outcome and correlates with airway inflammation better than FEV 1 alone.The score identifies a probable effect on mortality in response to CFTR modulators early in the treatment periodan endpoint that has proven elusive in prospective clinical trials and served as an obstacle in drug reimbursement negotiations with health care policymakers.

Background: . In CLEAR-108-a phase 3, randomised, open-label study-once-daily amikacin liposome inhalation suspension (ALIS) was noninferior to twice-daily tobramycin inhalation solution (TIS) in improving lung function i n patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection after 3 treatment cycles (28 days on/28 days off). The CLEAR-110 extension study (ClinicalTrials.gov: NCT01316276; EudraCT: 2011-0 0 0443-24) assessed long-term safety, tolerability, and efficacy of ALIS in eligible patients who completed CLEAR-108. Methods: . Patients received once-daily ALIS 590 mg for 12 treatment cycles (96 weeks). Patients were grouped by prior treatment: the "prior-ALIS" cohort received ALIS in CLEAR-108, and the "ALIS-naive" cohort received TIS in CLEAR-108. Results: . Overall, 206 patients (prior-ALIS, n = 92; ALIS-naive, n = 114) entered CLEAR-110 and received >= 1 dose of ALIS. Most patients (88.8%) experienced >= 1 treatment-emergent adverse event (TEAE) through day 672 (end of year 2). Most TEAEs (72.3%) were mild or moderate in severity. Severe TEAEs were reported in 31 patients (15.0%). Two life-threatening TEAEs (haemoptysis; intestinal obstruction) and 1 death (cardiac failure) were reported. Twenty-one patients (10.2%) discontinued treatment due to a TEAE (mostly infective pulmonary exacerbation of CF). Mean change from baseline in forced expiratory volume in 1 second percent predicted at day 672 was -3.1% (prior-ALIS, -4.0%; ALIS-naive, -2.3%). Mean change from baseline in sputum density of P. aeruginosa at day 672 was 0.02 (prior-ALIS, -0.16; ALIS-naive, 0.19) log CFU/g. Conclusions: . Long-term treatment with ALIS was well tolerated with a favourable adverse event profile and demonstrated continued antibacterial activity in CF patients with chronic P. aeruginosa infection. (C) 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

found a 1.10% (95% CI, -2.15, -0.05) decrease in ppFEV 1 and 1.02 (95% CI, 1.01, 1.03) increase in #IVdays per year for PwCF residing within 4 km of a RCS.Conclusions: This novel study of PwCF using 2016 UK CF Registry data suggests that living close to a RCS may be associated with a decrease in ppFEV 1 and an increase in #IVdays.Further analyses accounting for aerosols dispersion and fungal infections are ongoing to expand this work.If confirmed, these results may have important implications for the living environment of PwCF.

Of those never prescribed DNase, the multidisciplinary team (MDT) had discussed it with the patient in 25% of cases but it was not pursued; reasons included clinical stability (5%), alternative treatment commenced (21%), adherence issues (5%) or patient declined (32%).In those who had previously been prescribed DNase, the most common reasons for stopping included increased respiratory symptoms (36%) adherence (22%), and lack of perceived benefit (13%).In this group only 4% of patients did not tolerate DNase at test dose, and 50% of patients had tried it on more than one occasion after initial discontinuation.Conclusion: At our centre, 82% of patients are currently or have previously been prescribed DNase.Although the drug is well tolerated, reasons for stopping are complex and, despite retrial, many patients do not continue on the treatment.Those patients who have never been prescribed DNase have a better clinical status and take less inhaled therapies.As a result of this work, we now aim to implement a robust method of discussing indications for use and documenting reasons for discontinuation for all inhaled therapies at annual review.

Introduction In this long-term, postapproval, observational study, data from the US Cystic Fibrosis Foundation Patient Registry and the UK Cystic Fibrosis Registry were used to evaluate the impact of ivacaftor treatment on cystic fibrosis (CF) by comparing outcomes in ivacaftor-treated patients with those in matched untreated comparator patients. Registry data from up to 5 years of ivacaftor availability in the US and up to 4 years of availability in the UK were evaluated. Methods Starting in the first year of ivacaftor availability, ivacaftor-treated patients in each registry were matched 1:5 to comparator patients who never received ivacaftor. Clinical endpoints were evaluated in annual cross-sectional safety analyses. The key endpoints were death, organ transplants, pulmonary exacerbation, and hospitalization. Relative risks and 95% CIs were calculated to compare the ivacaftor and comparator cohorts in each registry. Results Here, we report the complete and final results of the annual cross-sectional safety analyses across the duration of the study, with up to 5 years of follow-up. Data show a pattern of lower risk of death, transplant, pulmonary exacerbation, and hospitalization among ivacaftor-treated patients in both registries. Conclusions Ivacaftor-treated patients had consistently favorable clinical outcomes relative to untreated comparators, and no new safety concerns were identified. While general limitations of observational research apply, these findings support disease modification by CF transmembrane conductance regulator (CFTR) modulator therapy with ivacaftor. Future research of novel CFTR modulators will need to explore alternative methods for comparator selection for evaluation of clinical data given the evolving landscape of CF treatment.

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Background Recent randomised clinical trials in bronchiectasis have failed to reach their primary endpoints, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis. Methods We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV1) of >= 100 mL from baseline. Results Cumulatively the three trials included 984 patients. Changes in FEV1, QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV1 in the azithromycin and aztreonam trials (r= -0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV1 is not a responsive measure in bronchiectasis. Conclusions Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders.

Introduction Airway clearance techniques (ACTs) are a gold standard of cystic fibrosis management; however, the majority of research evidence for their efficacy is of low standard; often attributed to the lack of sensitivity from outcome measures (OMs) used historically. This randomised controlled trial (RCT) investigates these standard OMs (sputum weight, forced expiratory volume in 1 s) and new OMs (electrical impedance tomography (EIT), multiple breath washout (MBW) and impulse oscillometry (IOS)) to determine the most useful measures of ACT.Methods and analysis This is a single-centre RCT with crossover design. Participants perform MBW, IOS and spirometry, and then are randomised to either rest or supervised ACT lasting 30–60 min. MBW, IOS and spirometry are repeated immediately afterwards. EIT and sputum are collected during rest/ACT. On a separate day, the OMs are performed with the other intervention. Primary endpoint is difference in change in OMs before and after ACT/rest. Sample size was calculated with 80% power and significance of 5% for each OM (target n=64).Ethics and dissemination Ethics approval was gained from the London–Chelsea Research Ethics Committee (reference 16/LO/0995, project ID 154635). Dissemination will involve scientific conference presentation and publication in a peer-reviewed journal.Trial registration numbers ISRCTN11220163 and NCT02721498.

BackgroundDefinition of Pseudomonas aeruginosa (Pa) microbiological status is essential for patients' inclusion in clinical trials. The aim of this study was to agree on the definitions of Pa infection status for initial infection, eradication and chronic infection to be used in clinical trials and to propose additional future study areas.MethodsAn exhaustive literature search was performed. The clinimetric properties of different definitions of Pa microbiological status were evaluated.ResultsHistorical studies have mostly used culture-based definitions, although some have also involved complementary anti-Pa antibodies. Clinimetric analysis showed great variability in the definitions used, leading to differences in reliability, validity, responsiveness to treatment and correlation with outcome measures.Use of serology for initial Pa infection and successful Pa eradication introduced a greater level of complexity as antibody tests are not standardised. Moreover, the chronology of the immune response to Pa antigenic determinants was not completely clear.Chronic Pa infection was characterized by high levels of antibodies and good concordance between culture results and serology.ConclusionsMicrobiological monitoring, regular sampling from the airways and standardization of culture methods remain essential requisites for microbiological definitions. Despite limitations, serology should be incorporated in the definitions of initial infection and eradication used in clinical trials to better classify patients at enrolment, mainly in non-expectorating children. This requires standardization of serological testing.

Background: As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics. Methods: A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations. Results: Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p < 0.001). After excluding new CF complications, there was no difference between cohorts (ERR = 1.04, 95% CI: 0.79-1.38, p = 0.785). Pulmonary exacerbations were common in CMS DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p = 0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively). Conclusions: There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its longterm safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety. (c) 2020 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Cystic fibrosis (CF) is the one of the most common inherited diseases. It affects around 10,000 people in the UK, and the median survival age is 47. Recent developments making use of longitudinal patient registry data are producing more detailed and relevant information about predicted life expectancy in CF based on current age and clinical measurements. The objective of this study was toconduct an online survey of adults with CF living in the UK using a web-based questionnaire to investigate: (i) if and how they access information on life expectancy; (ii) what they use it for; (iii) if they want more personalised information on life expectancy or the time until other milestones. The survey was advertised through the Cystic Fibrosis Trust using social media. There were 85 respondents, covering men (39%) and women (61%) aged 16-65. 75% had received information on life expectancy either from their CF care team (34%) or other sources (71%), the most common being the Cystic Fibrosis Trust website and research literature. Most people who received information found it to be beneficial and reported using it in a variety of ways, including to plan strategies for maintaining as best health as possible and to psychologically manage current health status. 82% of respondents were interested in more personalised information about their life expectancy, and participants also noted interest in other outcomes, including time to needing transplant or reaching a low level of lung function. Themes arising in text responses included the importance of good communication of information, the difficulty of relating general information to one's own circumstances, and a desire for increased information on factors that impact on survival in CF. As an outcome from this work, research is underway to establish how information on life expectancy can be presented to people with CF in an accessible way.

Aspergillus fumigatus is commonly found in the airways of patients with cystic fibrosis (CF), and allergic bronchopulmonary aspergillosis (ABPA) is the most recognized associated clinical condition. However, accurate diagnosis remains challenging, and there is a paucity of clinical trials to guide clinical management of fungal disease. The aim of this survey was to assess the variability in current practice across the UK in diagnosis and management of fungal lung disease in CF patients. A 21 question anonymous online survey was sent to 94 paediatric and adult CF consultants in the UK. The response rate was 60.6% (32 adult physicians, 25 pediatricians) with 55 full and 2 partially completed surveys. For a first diagnosis of ABPA 20 (35.1%) treat with prednisolone alone, 38 (66.7%) use prednisolone with itraconazole and 2 (3.5%) choose voriconazole. Only 5 (8.8%) treat with prednisolone alone for a 1st relapse, 33 (58%) used prednisolone with itraconazole. To reduce treatment, 21 (36.8%) decrease steroids to zero over time and maintain azole therapy, 18 (31.6%) stop the azole and steroid after a fixed time, and 5 (8.8%) stop the azole after a fixed time and maintain a small steroid dose. Thirty-eight (66.7%) respondents believe Aspergillus colonization of the airway can cause clinical deterioration, and 37 (66.1%) would treat this. Scedosporium apiospermum infection has been diagnosed and treated by 35 (61.4%) of respondents. Results of this survey highlight the variance in clinical practice and the limited evidence available to guide management of fungal infection in CF.

Background: Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5 years. Methods: Data from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity. Results: US analyses included 635 ivacaftor-treated patients and 1874 comparators followed for 5 years from year 1 of market availability (2012-2016). Evaluation of outcome patterns from pretreatment baseline (2011) through year 5 (2016), showed that relative to comparators, ivacaftor-treated patients had better preserved lung function (mean change in percent predicted FEV1, -0.7 percentage points with ivacaftor vs -8.3 percentage points in comparators) and improved nutritional status (mean body mass index change +2.4 kg/m(2) with ivacaftor vs +1.6 kg/m(2) in comparators). US patients treated with ivacaftor had significantly lower frequencies of exacerbations and hospitalizations in each of the 5 years of follow-up relative to pretreatment baseline and comparators. Favorable trends in CFRD and P. aeruginosa prevalence were also observed. Findings from the smaller UK registry were directionally similar to and consistent with US findings. Conclusions: This observational study represents the largest longitudinal analysis of patients treated with ivacaftor in a real-world setting. The findings support disease modification by CFTR modulation with ivacaftor. (C) 2019 The Authors. Published by Elsevier B.V.

IntroductionNon-invasive ventilation (NIV) is used in cystic fibrosis (CF) to support airway clearance techniques (ACTs) by augmenting tidal volumes and reducing patient effort. However, the evidence base for this is limited. We hypothesised that NIV, in addition to usual ACT, would increase sputum clearance. In addition, we investigated ease of sputum clearance (EoC), work of breathing (WoB) and NIV tolerability.MethodsAdults with CF (16+ years) at the end of hospitalisation for a pulmonary exacerbation were randomised to a cross-over trial of NIV-supported ACT or ACT alone in two consecutive days. No other changes to standard care were made. The primary outcome was the total 24-hour expectorated sputum wet weight after the intervention. Spirometry was completed pre-treatment and post-treatment. Oxygen saturations were measured pre-treatment, during treatment and post-treatment. EoC and WoB were assessed using Visual Analogue Scale.Results14 subjects completed the study (7 male, mean age 35 [SD 17] years, mean forced expiratory volume in 1 s [FEV1] 49 [20] % predicted). The difference between treatment regimens was −0.98 g sputum (95% CI −11.5 to 9.6, p=0.84) over 24 hours. During treatment oxygen saturations were significantly higher with NIV-supported ACT (mean difference 2.0, 95% CI 0.9 to 2.6, p=0.0004). No other significant differences were found in post-treatment FEV1, EoC, WoB, oxygen saturations or subject preference.ConclusionsThere was no difference in treatment effect between NIV-supported ACT and ACT alone, although the study was underpowered. Oxygen saturations were significantly higher during NIV-supported ACT, but with no effect on post-treatment saturations. NIV was well tolerated.Trial registration numberNCT01885650.