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Objective: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with those of the general population and assess the effect of the introduction of disease‐modifying treatment. Design: A population‐based longitudinal study, 2003–17. Setting: United Kingdom. Population: Women aged 15–44 years in the UK cystic fibrosis (CF) Registry compared with women in England and Wales. Methods: We calculated pregnancy and live‐birth rates for the CF population and the general population of England and Wales. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre‐pregnancy lung function and nutritional status and child gestational age. Main outcome measures: Pregnancy and live‐birth rates and child gestational age. Results: Of 3831 women with CF, 661 reported 818 pregnancies. Compared with the general population, the pregnancy rate was 3.3 times lower in the CF population (23.5 versus 77.7 per 1000 woman‐years); the live‐birth rate was 3.5 times lower (17.4 versus 61.4 per 1000 woman‐years) with 70% of pregnancies in CF women resulting in live births; termination of pregnancy rates were also lower (9% versus 22%). Pregnancy rates increased post‐ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1000 woman‐years. There was no association between pre‐pregnancy lung function/nutrition status and gestational age. Conclusions: Pregnancy rates in women with CF are about one‐third of the rates in the general population with favourable outcomes, and increased for eligible women post‐ivacaftor. Pregnancy rates in women with CF are about a third of the rate in England and Wales with 70% live births. Ivacaftor increases the rate. [ABSTRACT FROM AUTHOR]

Background: Better use of healthcare systems data, collected as part of interactions between patients and the healthcare system, could transform planning and conduct of randomised controlled trials. Multiple challenges to widespread use include whether healthcare systems data captures sufficiently well the data traditionally captured on case report forms. "Data Utility Comparison Studies" (DUCkS) assess the utility of healthcare systems data for RCTs by comparison to data collected by the trial. Despite their importance, there are few published UK examples of DUCkS., Methods-And-Results: Building from ongoing and selected recent examples of UK-led DUCkS in the literature, we set out experience-based considerations for the conduct of future DUCkS. Developed through informal iterative discussions in many forums, considerations are offered for planning, protocol development, data, analysis and reporting, with comparisons at "patient-level" or "trial-level", depending on the item of interest and trial status., Discussion: DUCkS could be a valuable tool in assessing where healthcare systems data can be used for trials and in which trial teams can play a leading role. There is a pressing need for trials to be more efficient in their delivery and research waste must be reduced. Trials have been making inconsistent use of healthcare systems data, not least because of an absence of evidence of utility. DUCkS can also help to identify challenges in using healthcare systems data, such as linkage (access and timing) and data quality. We encourage trial teams to incorporate and report DUCkS in trials and funders and data providers to support them., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CB is now employed at Insitro, South San Francisco, CA. Insitro had no involvement in the design or implementation of the work presented here., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies have demonstrated a higher risk of developing colorectal cancer (CRC) in individuals with Cystic Fibrosis (CF), and also a potentially increased risk in carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. Life expectancy for those with CF is rising, increasing the number at risk of developing CRC., Methods: The incidence of CRC amongst individuals with CF was calculated using data from CORECT-R and linked UK CF Registry and Secondary User Services (SUS) data. Crude, age-specific and age-standardised rates were compared to those without CF. The presence of CFTR mutations in individuals with CRC was assessed using 100,000 Genomes Project data., Findings: The crude incidence rate of CRC in the CF population was 0.29 per 1,000 person-years (28 cases). The CF population were significantly younger than those without (median age at CRC diagnosis 52 years versus 73 years; p<0·01). When age-adjusted, there was a 5-fold increased CRC incidence amongst individuals with CF compared to those without (SIR 5.0 95%CI 3.2-6.9). When compared to other population studies the overall prevalence of CFTR mutations in the CRC population was significantly higher than expected (p<0·01)., Interpretation: CF is linked to an increased risk of CRC. The incidence of CFTR mutations in the CRC population is higher than would be expected, suggesting an association between CFTR function and CRC risk. Further research is needed to develop effective screening strategies for these populations., Funding: Cancer Research UK (grants C23434/A23706 & C10674/A27140)., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Cystic fibrosis (CF) is a life-threatening genetic disease, affecting around 10 500 people in the UK. Precision medicines have been developed to treat specific CF-gene mutations. The newest, elexacaftor/tezacaftor/ivacaftor (ELEX/TEZ/IVA), has been found to be highly effective in randomised controlled trials (RCTs) and became available to a large proportion of UK CF patients in 2020. Understanding the potential health economic impacts of ELEX/TEZ/IVA is vital to planning service provision., Methods: We combined observational UK CF Registry data with RCT results to project the impact of ELEX/TEZ/IVA on total days of intravenous (IV) antibiotic treatment at a population level. Registry data from 2015 to 2017 were used to develop prediction models for IV days over a 1-year period using several predictors, and to estimate 1-year population total IV days based on standards of care pre-ELEX/TEZ/IVA. We considered two approaches to imposing the impact of ELEX/TEZ/IVA on projected outcomes using effect estimates from RCTs: approach 1 based on effect estimates on FEV 1 % and approach 2 based on effect estimates on exacerbation rate., Results: ELEX/TEZ/IVA is expected to result in significant reductions in population-level requirements for IV antibiotics of 16.1% (~17 800 days) using approach 1 and 43.6% (~39 500 days) using approach 2. The two approaches require different assumptions. Increased understanding of the mechanisms through which ELEX/TEZ/IVA acts on these outcomes would enable further refinements to our projections., Conclusions: This work contributes to increased understanding of the changing healthcare needs of people with CF and illustrates how Registry data can be used in combination with RCT evidence to estimate population-level treatment impacts., Competing Interests: Competing interests: SBC reports personal fees and other from Chiesi Pharmaceuticals, non-financial support and other from Vertex, other from Zambon, other from Insmed, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes. Methods Data from 22 countries prior to 13 th December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequalae following SARS-CoV-2 infection. Multivariable logistic regression was used to investigate factors associated with clinical progression to severe COVID-19, using the primary outcome of hospitalisation with supplemental oxygen., Results: SARS-CoV-2 was reported in 1555 people with CF, 1452 were included in the analysis. One third were aged <18 years, and 9.4% were solid-organ transplant recipients. 74.5% were symptomatic and 22% were admitted to hospital. In the non-transplanted cohort, 39.5% of patients with ppFEV1<40% were hospitalised with oxygen verses 3.2% with ppFEV >70%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, underweight body mass index, and CF-related diabetes. Prescription of highly effective CFTR modulator therapies was associated with a significantly reduced odds of being hospitalised with oxygen (AOR 0.43 95%CI 0.31-0.60 p<0.001). Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and was independently associated with the primary outcome (Adjusted OR 2.45 95%CI 1.27-4.71 p=0.007)., Conclusions: This is the first study to show that there is a protective effect from the use of CFTR modulator therapy and that people with CF from an ethnic minority are at more risk of severe infection with SARS-CoV-2., Competing Interests: COI Statement All authors declare no conflicts of interest in relationship to this work. Outside of this work the following authors declare payments or honoraria to them or their institution for a combination of lectures, presentations, educational events, advisory boards, steering groups, grants or consultancy fees: SC-Vertex, Chiesi, Profile, Zambon. RC- Vertex, P-RB – Astra-Zeneca, Boehringer Ingelheim, GSK, Insmed, Chiesi, Pfizer, Vertex, Zambon. I deM – Vertex,LN – Vertex, Boehringer,LVS-F – Vertex, AS -Vertex., (Copyright © 2022. Published by Elsevier B.V.)

Background: Despite the importance of reducing treatment burden for people with cystic fibrosis (CF), it has not been fully understood as a concept. This study aims to quantify the treatment burden perceived by CF adults and explore the association between different validated treatment burden measures., Methods: This is a cross-sectional observational study of CF adults attending a single large UK adult center. Participants completed an online survey that contained three different treatment burden scales; CF Questionnaire-Revised (CFQ-R) subscale, CF Quality of Life (CFQoL) subscale, and the generic multimorbidity treatment burden questionnaire (MTBQ)., Results: Among 101 participants, the median reported treatment burden by the CFQ-R subscale was 55.5 (IQR 33.3 - 66.6), the CFQoL subscale was 66.6 (IQR 46.6 - 86.6), and the MTBQ reversed global score was 84.6 (IQR 73.1 - 92.3). No correlation was found between respondents' demographic or clinical variables and treatment burden measured via any of the three measures. All treatment burden measures showed correlations against each other. More treatments were associated with high treatment burden as measured by the CFQ-R, CFQoL subscales, and the MTBQ. However, longer treatment time and more complex treatment plans were correlated with high treatment burden as measured by the CFQ-R and CFQoL subscales, but not with the MTBQ., Conclusions: Treatment burden is a substantial issue in CF. Currently, the only available way to evaluate it is with the CF-specific quality of life measure treatment burden subscales (CFQ-R and CFQoL); both indicated that treatment burden increases with more treatments, longer treatment time, and more complex treatments., Competing Interests: Competing interests: RA, JA, RCo, DO, JM, RCa, DT, SC, NS and JW have no direct conflicts of interest to declare in relation to this study. Outside of the submitted work, SC has served on advisory boards and/or given educational lectures for which she or her institution have received fees for (Vertex, Chiesi, and Profile Pharma). NS has served on advisory boards and/or given educational lectures for which he has received consultancy fees (Vertex, Gilead, Chiesi, Zambon, Roche, and Menarini).

Objective: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with those of the general population and assess the effect of the introduction of disease-modifying treatment., Design: A population-based longitudinal study, 2003-17., Setting: United Kingdom., Population: Women aged 15-44 years in the UK cystic fibrosis (CF) Registry compared with women in England and Wales., Methods: We calculated pregnancy and live-birth rates for the CF population and the general population of England and Wales. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre-pregnancy lung function and nutritional status and child gestational age., Main Outcome Measures: Pregnancy and live-birth rates and child gestational age., Results: Of 3831 women with CF, 661 reported 818 pregnancies. Compared with the general population, the pregnancy rate was 3.3 times lower in the CF population (23.5 versus 77.7 per 1000 woman-years); the live-birth rate was 3.5 times lower (17.4 versus 61.4 per 1000 woman-years) with 70% of pregnancies in CF women resulting in live births; termination of pregnancy rates were also lower (9% versus 22%). Pregnancy rates increased post-ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1000 woman-years. There was no association between pre-pregnancy lung function/nutrition status and gestational age., Conclusions: Pregnancy rates in women with CF are about one-third of the rates in the general population with favourable outcomes, and increased for eligible women post-ivacaftor., Tweetable Abstract: Pregnancy rates in women with CF are about a third of the rate in England and Wales with 70% live births. Ivacaftor increases the rate., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes., Methods: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis., Results: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function)., Conclusion: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes., Competing Interests: Conflict of interest: A. Jung has nothing to disclose. Conflict of interest: A. Orenti has nothing to disclose. Conflict of interest: F. Dunlevy reports support for the present manuscript from Chiesi Farmaceutici SpA. Conflict of interest: E. Aleksejeva has nothing to disclose. Conflict of interest: E. Bakkeheim has nothing to disclose. Conflict of interest: V. Bobrovnichy has nothing to disclose. Conflict of interest: S.B. Carr reports receiving speaker honoraria from Vertex and Chiesi, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Vertex, Profile Pharma and Chiesi, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from UK CF Trust; PI for Pharmacovigilance study, payment to institution from Pharmaxis, outside the submitted work. Conflict of interest: C. Colombo has nothing to disclose. Conflict of interest: H. Corvol has nothing to disclose. Conflict of interest: R. Cosgrif declares outside the submitted work to be the director of the Cystic Fibrosis Trust. Conflict of interest: G. Daneau has nothing to disclose. Conflict of interest: D. Dogru has nothing to disclose. Conflict of interest: P. Drevinek reports grants or contracts from Ministry of Health, Czech Republic, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Vertex Pharmaceuticals and Actelion Pharmaceuticals, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Vertex Pharmaceuticals, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Society for Medical Microbiology, outside the submitted work. Conflict of interest: A.D. Vukic has nothing to disclose. Conflict of interest: I. Fajac reports grants or contracts from Boehringer Ingelheim, Celtaxsys, Corbus Pharmaceuticals, and Vertex Pharmaceuticals, outside the submitted work; consulting fees from Boehringer Ingelheim and Vertex Pharmaceuticals, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Vertex Pharmaceuticals and Boehringer Ingelheim, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for European Cystic Fibrosis Society. Conflict of interest: A. Fox support for the present manuscript from Chiesi Farmaceutici SpA. Conflict of interest: S. Fustik has nothing to disclose. Conflict of interest: V. Gulmans has nothing to disclose. Conflict of interest: S. Harutyunyan has nothing to disclose. Conflict of interest: E. Hatziagorou has nothing to disclose. Conflict of interest: I. Kasmi has nothing to disclose. Conflict of interest: H. Kayserová has nothing to disclose. Conflict of interest: E. Kondratyeva reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from All-Russian online school with international participation, outside the submitted work. Conflict of interest: U. Krivec has nothing to disclose. Conflict of interest: H. Makukh has nothing to disclose. Conflict of interest: K. Malakauskas has nothing to disclose. Conflict of interest: E.F. McKone reports grants or contracts from vertex, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Vertex Pharmaceuticals and Roche Pharmaceuticals, outside the submitted work; support for attending meetings and/or travel from A Menarini, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Insmed and Janssen Pharmaceuticals, outside the submitted work. Conflict of interest: M. Mei-Zahav has nothing to disclose. Conflict of interest: I. de Monestrol reports grant from Vertex for an academic research study regarding gastrointestinal outcome in CF patients taking Orkambi medication, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Swedish CF Registry and the Swedish Society of Medicine's CF working group. Conflict of interest: H.V. Olesen has nothing to disclose. Conflict of interest: R. Padoan has nothing to disclose. Conflict of interest: T. Parulava has nothing to disclose. Conflict of interest: M.D. Pastor-Vivero has nothing to disclose. Conflict of interest: L. Pereira has nothing to disclose. Conflict of interest: G. Petrova reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from TEVA Pharmaceuticals, Mylan and Alvogen, outside the submitted work. Conflict of interest: A. Pfleger has nothing to disclose. Conflict of interest: L. Pop has nothing to disclose. Conflict of interest: J.G. van Rens has nothing to disclose. Conflict of interest: M. Rodić has nothing to disclose. Conflict of interest: M. Schlesser has nothing to disclose. Conflict of interest: V. Storms has nothing to disclose. Conflict of interest: O. Turcu has nothing to disclose. Conflict of interest: L. Woźniacki has nothing to disclose. Conflict of interest: P. Yiallouros has nothing to disclose. Conflict of interest: A. Zolin has nothing to disclose. Conflict of interest: D.G. Downey has nothing to disclose. Conflict of interest: L. Naehrlich reports support for the present manuscript from Chiesi Farmaceutici SpA; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ArticulateScience LLC, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Trial Steering committee of CF Storm, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Society for German CF Registry European CF Patient Registry, outside the submitted work; other financial or nonfinancial interests from Vertex Pharmaceuticals and Boehringer Ingelheim; Institutional fees for site participation (PI) in clinical trials from Vertex Pharmaceuticals and Boehringer Ingelheim., (Copyright ©The authors 2021.)

Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF)., Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection., Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133)., Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination., Competing Interests: Declaration of Competing Interest Dr. Naehrlich reports that he has received institutional fees for site participation in clinical trials from Vertex Pharmaceuticals and Boehringer Ingelheim; Dr. Orenti has nothing to disclose; Dr. Dunlevy reports institutional grants from Chiesi, during the conduct of the study; Dr. Kasmi has nothing to disclose; Dr. Harutyunyan has nothing to disclose; Dr. Pfleger has nothing to disclose; Dr. Bobrovnichy has nothing to disclose;Dr. Keegan has nothing to disclose; Dr. Daneau has nothing to disclose; Dr. Petrova has nothing to disclose; Dr. Bambir has nothing to disclose; Dr. Vukić Dugac has nothing to disclose; Dr. Tješić-Drinković has nothing to disclose; Dr. Yiallouros has nothing to disclose; Dr. Drevinek reports personal fees from Vertex Pharmaceuticals, outside the submitted work; Prof. Milan Macek reports grants from Vertex Pharmaceuticals,  outside the submitted workr r; Mrs. Bilkova has nothing to disclose; Dr. Olesen has nothing to disclose; Dr. Burgel reports personal fees from Astra-Zeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GSK, personal fees from Insmed, personal fees from Novartis, personal fees from Pfizer, grants and personal fees from Vertex, personal fees from Zambon, outside the submitted work; Dr. Corvol has nothing to disclose; Ms. Lemmonier has nothing to disclose; Dr. Parulava has nothing to disclose; Dr. Hatziagorou has nothing to disclose; Dr. Diamantea has nothing to disclose; Dr. Párniczky has nothing to disclose; G. Fletcher has nothing to disclose; Prof. McKone reports travel support from A Menarini, speaker fees from Roche Pharmaceuticals, consultancy fees from Insmed, consultancy fees from Janssen Pharmaceuticals, grants to institution and consultancy fees from Vertex, outside the submitted work; Dr. Mei-Zahav has nothing to disclose; Dr. Padoan has nothing to disclose; Dr. Salvatore has nothing to disclose; Dr. Colombo has nothing to disclose; Dr. Aleksejeva has nothing to disclose; Dr. Malakauskas has nothing to disclose; Dr. Schlesser has nothing to disclose; Dr. Fustik has nothing to disclose; Dr. Turcu has nothing to disclose; V. Gulmans has nothing to disclose; D. Zomer-van Ommen has nothing to disclose; Dr. Wathne has nothing to disclose; Dr. Bakkeheim has nothing to disclose; Dr. Wozniacki has nothing to disclose; Dr. Pereira has nothing to disclose; Dr. Pop has nothing to disclose; Dr. Kondratyeva has nothing to disclose; Dr. Amelina has nothing to disclose; Dr. Zhekaite has nothing to disclose; Dr. O. Simonova has nothing to disclose; Dr. Kashirskaya has nothing to disclose; Dr. Rodic has nothing to disclose; Dr. Kayserova has nothing to disclose; Dr. Krivec has nothing to disclose; Dr. Mondejar-Lopez has nothing to disclose; Dr. Pastor-Vivero has nothing to disclose; Dr. de Monestrol reports grants from Vertex, outside the submitted work; Dr. Lindblad has nothing to disclose; Dr. Dogru has nothing to disclose; Dr. Gokdemir has nothing to disclose; Dr. Pekcan has nothing to disclose; Dr. Makukh has nothing to disclose; Dr. Brownlee has nothing to disclose; Ms. Cosgriff has nothing to disclose; Mr. McClenaghan has nothing to disclose; Dr. Carr reports personal fees from Chiesi Pharmaceuticals, personal fees and non-financial support from Vertex, personal fees from Zambon, personal fees from Insmed, outside the submitted work; Dr. Lammertyn has nothing to disclose; Dr. Zolin has nothing to disclose; Ms.. Fox reports grants from ECFS, during the conduct of the study; Mr Krasnyk has nothing to disclose; Mrs. Van Rens has nothing to disclose; Dr. van Koningsbruggen-Rietschel reports grants and personal fees from Algipharma (HORIZON2020), personal fees from Deutsches Zentrum für Infektionsforschung, personal fees from Antabio, personal fees from Proteostasis, personal fees from Roche, personal fees from Vertex, outside the submitted work; Dr. Jung reports grants from Chiesi Pharmaceuticals, during the conduct of the study., (Copyright © 2021. Published by Elsevier B.V.)