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Background: Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on in vitro data in the USA for those carrying at least one of 177 rare CFTR (cystic fibrosis transmembrane conductance regulator) variants., Methods: PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV 1 ) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively., Results: A total of 1791 individuals aged ≥6 years with rare CFTR variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV 1 % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators., Conclusions: Extension of the ETI label to rare CFTR variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations., Competing Interests: Conflict of interest: E.A. Cromwell reports support for the present study from the Cystic Fibrosis Foundation. J.S. Ostrenga has nothing to disclose. D.B. Sanders reports support for the present study from the Cystic Fibrosis Foundation (CFF), grants from the CFF, consultancy fees from the CFF for roles on the Registry Committee, Data Safety Monitoring Board (DSMB) and Grant Review Committee, and participation on a DSMB or Advisory Board with the CFF. W. Morgan reports support for the present study from the Cystic Fibrosis Foundation (CFF) as a paid consultant for work on the CFF Registry Committee, covering a range of activities including papers, analyses and reviews of protocol/data requests; additionally, grants were received from the NIH/NHLBI for the ORBEX study (Site PI and Executive Committee) and the Tucson Children's Respiratory Study, from Boston Children's Hospital/Harvard for consultancy to the PARK study (NIH/NIAID), and from the CFF for Data Safety Monitoring Board (DSMB) infrastructure; consultancy fees were also received from the CFF for DSMB-related activities; payment for lectures was received from the American College of Chest Physicians for the 2022 Pediatric Pulmonology Board Prep Course; support for attending meetings was provided by the CFF for travel to the CFF DSMB meeting in April 2023; participation on a DSMB or Advisory Board includes serving as Chair of the CFF DSMB, chairing several DSMBs for CF clinical research trials and participation on the NIH/NHLBI PRIMERO Observational Study Monitoring Board. C. Castellani reports participation on a Data Safety Monitoring Board or Advisory Board with Vertex and Chiesi. R. Szczesniak reports payment or honoraria for lectures, presentations, manuscript writing or educational events from the Cystic Fibrosis Foundation (CFF) Patient Registry Committee; additionally, support for attending meetings and/or travel was provided by the CFF Patient Registry Committee. P-R. Burgel reports grants or contracts from GSK and Vertex, and consultancy fees from AstraZeneca, Chiesi, GSK, Insmed, MSD, Sanofi, Viatris, Vertex and Zambon., (Copyright ©The authors 2024.)

Background: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research., Methods: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion., Results: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder., Conclusions: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities., Competing Interests: Conflict of interest: C. Bai has nothing to disclose. Conflict of interest: S.H. Chotirmall has nothing to disclose. Conflict of interest: J. Rello has nothing to disclose. Conflict of interest: G.A. Alba has nothing to disclose. Conflict of interest: L.C. Ginns has nothing to disclose. Conflict of interest: J.A. Krishnan reports grants from National Institutes of Health, Regeneron/Department of Health and Human Services, and Verily for COVID-19 studies outside the submitted work. Conflict of interest: R. Rogers has nothing to disclose. Conflict of interest: E. Bendstrup reports grants and personal fees from Hofmann la Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: P-R. Burgel reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Insmed, Novartis, Pfizer, Teva and Zambon, and grants and personal fees from Vertex and GSK, outside the submitted work. Conflict of interest: J.D. Chalmers reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Glaxosmithkline, Insmed and Novartis, personal fees from Chiesi and Zambon, and grants from Gilead, outside the submitted work. Conflict of interest: A. Chua has nothing to disclose. Conflict of interest: K.A. Crothers has nothing to disclose. Conflict of interest: A. Duggal has nothing to disclose. Conflict of interest: Y.W. Kim has nothing to disclose. Conflict of interest: J.G. Laffey has nothing to disclose. Conflict of interest: C.M. Luna has nothing to disclose. Conflict of interest: M.S. Niederman reports other funding from Abbvie and Merck, outside the submitted work. Conflict of interest: G. Raghu reports consultant fees from Boerhinger Ingelheim, Roche-Genentech, Blade therapeutics, PureTech Health and Humanetics corporation. Conflict of interest: J.A. Ramirez has nothing to disclose. Conflict of interest: J. Riera has nothing to disclose. Conflict of interest: O. Roca provides consultancy to Hamilton Medical but did not receive any personal fees. All compensations were received by the Institute of Research of his institution. He also reports personal fees from Air Liquide, outside the submitted work. Conflict of interest: M. Tamae-Kakazu has nothing to disclose. Conflict of interest: A. Torres has nothing to disclose. Conflict of interest: R.R. Watkins has nothing to disclose. Conflict of interest: M. Barrecheguren reports speaker fees from Grifols, Menarini, CSL Behring, Boehringer Ingelheim and GSK, and consulting fees from GSK and Novartis, outside the submitted work. Conflict of interest: M. Belliato has nothing to disclose. Conflict of interest: H.A. Chami reports grants, personal fees and non-financial support from Pfizer, and personal fees from Boehringer Ingelheim, MSD, Novartis, Mundipharma and AstraZeneca, outside the submitted work. Conflict of interest: R. Chen has nothing to disclose. Conflict of interest: G.A. Cortes Puentes has nothing to disclose. Conflict of interest: C. Delacruz has nothing to disclose. Conflict of interest: M.M. Hayes has nothing to disclose. Conflict of interest: L.M.A. Heunks reports grants from Liberate medical, USA, personal fees from Getinge Critical Care, Sweden, and grants and personal fees from Orion Pharma, Finland, outside the submitted work. Conflict of interest: S.R. Holets has nothing to disclose. Conflict of interest: C.L. Hough has nothing to disclose. Conflict of interest: S. Jagpal was a sub-investigator for the RWJ New Brunswick Remdesivir study. Conflict of interest: S. Jeon has nothing to disclose. Conflict of interest: K. Johkoh has nothing to disclose. Conflict of interest: M.M. Lee has nothing to disclose. Conflict of interest: J. Liebler has nothing to disclose. Conflict of interest: G.N. McElvaney has nothing to disclose. Conflict of interest: A. Moskowitz has nothing to disclose. Conflict of interest: R.A. Oeckler has nothing to disclose. Conflict of interest: I. Ojanguren reports grants and personal fees from AstraZeneca and Chiesi, personal fees from Boehringer Ingelheim, Novartis, GSK, MSD, BIAL, Mundipharma and TEVA, and grants from Menarini, outside the submitted work. Conflict of interest: A. O'Regan has nothing to disclose. Conflict of interest: M.W. Pletz has nothing to disclose. Conflict of interest: C.K. Rhee reports personal fees from MSD, AstraZeneca, GSK Novartis, Takeda, Mundipharma, Boehringer-Ingelheim, Teva, Sanofi and Bayer, outside the submitted work. Conflict of interest: M.J. Schultz's institution and department participated, and participates in, international studies of remdisivir. Participation was without financial compensations, etc., and also did not and will not lead to authorships on manuscripts from these studies. Conflict of interest: E. Storti has nothing to disclose. Conflict of interest: C. Strange has nothing to disclose. Conflict of interest: C.C. Thomson has nothing to disclose. Conflict of interest: F.J. Torriani has nothing to disclose. Conflict of interest: X. Wang has nothing to disclose. Conflict of interest: W. Wuyts has nothing to disclose. Conflict of interest: T. Xu has nothing to disclose. Conflict of interest: D. Yang has nothing to disclose. Conflict of interest: Z. Zhang has nothing to disclose. Conflict of interest: K.C. Wilson has nothing to disclose., (Copyright ©ERS 2020.)

Information is lacking on the clinical impact of the novel coronavirus, SARS-CoV-2, on people with cystic fibrosis (CF). Our aim was to characterise SARS-CoV-2 infection in people with cystic fibrosis., Methods: Anonymised data submitted by each participating country to their National CF Registry was reported using a standardised template, then collated and summarised., Results: 40 cases have been reported across 8 countries. Of the 40 cases, 31 (78%) were symptomatic for SARS-CoV-2 at presentation, with 24 (60%) having a fever. 70% have recovered, 30% remain unresolved at time of reporting, and no deaths have been submitted., Conclusions: This early report shows good recovery from SARS-CoV-2 in this heterogeneous CF cohort. The disease course does not seem to differ from the general population, but the current numbers are too small to draw firm conclusions and people with CF should continue to strictly follow public health advice to protect themselves from infection., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare relating to this work., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To develop disease-specific recommendations for the diagnosis and management of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (EGPA)., Methods: The EGPA Consensus Task Force experts comprised 8 pulmonologists, 6 internists, 4 rheumatologists, 3 nephrologists, 1 pathologist and 1 allergist from 5 European countries and the USA. Using a modified Delphi process, a list of 40 questions was elaborated by 2 members and sent to all participants prior to the meeting. Concurrently, an extensive literature search was undertaken with publications assigned with a level of evidence according to accepted criteria. Drafts of the recommendations were circulated for review to all members until final consensus was reached., Results: Twenty-two recommendations concerning the diagnosis, initial evaluation, treatment and monitoring of EGPA patients were established. The relevant published information on EGPA, antineutrophil-cytoplasm antibody-associated vasculitides, hypereosinophilic syndromes and eosinophilic asthma supporting these recommendations was also reviewed., Discussion: These recommendations aim to give physicians tools for effective and individual management of EGPA patients, and to provide guidance for further targeted research., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA+) production in SSc patients in a candidate gene study. This gene has been proposed to have a critical role in IL-17-driven autoimmunity in human diseases., Methods: In order to confirm the association between CCR6 and ATA+ SSc patients, we performed an independent replication study in populations of European ancestry. We studied two CCR6 genetic variants (rs968334 and rs3093024) in a total of 901 ATA+ SSc cases, 3,258 ATA- SSc cases and 7,865 healthy controls and compared allelic frequencies for those SNPs in ATA+ SSc with healthy controls and also with ATA- SSc patients., Results: The comparison performed between ATA+ SSc patients and healthy controls showed significant association with SNP rs968334 (p=4.88x10(-2), OR=1.11). When we compared ATA+ SSc cases with ATA- SSc, both SNPs, rs3093024 and rs968334, showed significant associations (p=2.89x10(-2), OR=1.13; p=1.69x10(-2), OR=1.15). Finally, in order to increase even more sample size and statistical power, we meta-analysed our study with the previous reported and found a significant association between SNP rs3093024 and ATA+ SSc patients (p=1.00x10(-4), OR=1.16) comparing with healthy controls., Conclusions: Our work confirms the association of CCR6 gene and ATA+ SSc patients.