{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:44:44Z","timestamp":1793303084048,"version":"4.5.0"},"reference-count":134,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000272","name":"DH | National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012068","name":"Health and Care Research Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012068","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We are currently witnessing transformative change for people with cystic fibrosis with the introduction of small molecule, mutation-specific drugs capable of restoring function of the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). However, despite being a single gene disorder, there are multiple cystic fibrosis-causing genetic variants; mutation-specific drugs are not suitable for all genetic variants and also do not correct all the multisystem clinical manifestations of the disease. For many, there will remain a need for improved treatments. Those patients with gene variants responsive to CFTR modulators may have found these therapies to be transformational; research is now focusing on safely reducing the burden of symptom-directed treatment. However, modulators are not available in all parts of the globe, an issue which is further widening existing health inequalities. For patients who are not suitable for- or do not have access to- modulator drugs, alternative approaches are progressing through the trials pipeline. There will be challenges encountered in design and implementation of these trials, for which the established global CF infrastructure is a major advantage. Here, the Cystic Fibrosis National Research Strategy Group of the UK NIHR Respiratory Translational Research Collaboration looks to the future of cystic fibrosis therapies and consider priorities for future research and development.<\/jats:p>","DOI":"10.1038\/s41467-023-36244-2","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T15:04:04Z","timestamp":1675868644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Future therapies for cystic fibrosis"],"prefix":"10.1038","volume":"14","author":[{"given":"Lucy","family":"Allen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0580-2478","authenticated-orcid":false,"given":"Siobhan B.","family":"Carr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7937-2728","authenticated-orcid":false,"given":"Gwyneth","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Downey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Egan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0580-0432","authenticated-orcid":false,"given":"Julian T.","family":"Forton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Haworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-0058","authenticated-orcid":false,"given":"Alexander","family":"Horsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5494-5438","authenticated-orcid":false,"given":"Alan R.","family":"Smyth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Southern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3506-1199","authenticated-orcid":false,"given":"Jane C.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"36244_CR1","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/S2213-2600(16)00053-9","volume":"4","author":"C Castellani","year":"2016","unstructured":"Castellani, C., Massie, J., Sontag, M. & Southern, K. W. Newborn screening for cystic fibrosis. Lancet Respir. Med. 4, 653\u2013661 (2016).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR2","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jcf.2016.12.012","volume":"16","author":"J Barben","year":"2017","unstructured":"Barben, J. et al. The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe. J. Cyst. Fibros. 16, 207\u2013213 (2017).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR3","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1136\/archdischild-2011-300449","volume":"96","author":"FN Dijk","year":"2011","unstructured":"Dijk, F. N., McKay, K., Barzi, F., Gaskin, K. J. & Fitzgerald, D. A. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch. Dis. Child. 96, 1118\u20131123 (2011).","journal-title":"Arch. Dis. Child."},{"key":"36244_CR4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jcf.2004.12.002","volume":"4","author":"E Kerem","year":"2005","unstructured":"Kerem, E., Conway, S., Elborn, S., Heijerman, H. & Consensus, C. Standards of care for patients with cystic fibrosis: a European consensus. J. Cyst. Fibros. 4, 7\u201326 (2005).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR5","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.jcf.2018.02.006","volume":"17","author":"C Castellani","year":"2018","unstructured":"Castellani, C. et al. ECFS best practice guidelines: the 2018 revision. J. Cyst. Fibros. 17, 153\u2013178 (2018).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR6","first-page":"CD001127","volume":"3","author":"C Yang","year":"2021","unstructured":"Yang, C. & Montgomery, M. Dornase alfa for cystic fibrosis. Cochrane Database Syst. Rev. 3, CD001127 (2021).","journal-title":"Cochrane Database Syst. Rev."},{"key":"36244_CR7","first-page":"CD001506","volume":"9","author":"P Wark","year":"2018","unstructured":"Wark, P. & McDonald, V. M. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst. Rev. 9, CD001506 (2018).","journal-title":"Cochrane Database Syst. Rev."},{"key":"36244_CR8","first-page":"CD008649","volume":"5","author":"SJ Nevitt","year":"2020","unstructured":"Nevitt, S. J., Thornton, J., Murray, C. S. & Dwyer, T. Inhaled mannitol for cystic fibrosis. Cochrane Database Syst. Rev. 5, CD008649 (2020).","journal-title":"Cochrane Database Syst. Rev."},{"key":"36244_CR9","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/S2213-2600(19)30187-0","volume":"7","author":"F Ratjen","year":"2019","unstructured":"Ratjen, F. et al. Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Respir. Med. 7, 802\u2013809 (2019).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR10","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S2213-2600(21)00546-4","volume":"10","author":"H Tiddens","year":"2022","unstructured":"Tiddens, H. et al. The effect of inhaled hypertonic saline on lung structure in children aged 3-6 years with cystic fibrosis (SHIP-CT): a multicentre, randomised, double-blind, controlled trial. Lancet Respir. Med. 10, 669\u2013678 (2022).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR11","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1164\/rccm.201303-0429OC","volume":"187","author":"G Thabut","year":"2013","unstructured":"Thabut, G. et al. Survival benefit of lung transplant for cystic fibrosis since lung allocation score implementation. Am. J. Respiratory Crit. Care Med. 187, 1335\u20131340 (2013).","journal-title":"Am. J. Respiratory Crit. Care Med."},{"key":"36244_CR12","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.jcf.2018.03.001","volume":"17","author":"EC Dasenbrook","year":"2018","unstructured":"Dasenbrook, E. C. & Sawicki, G. S. Cystic fibrosis patient registries: a valuable source for clinical research. J. Cyst. Fibros. 17, 433\u2013440 (2018).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR13","unstructured":"Trust, C. C. F. Trust registry annual report data 2020 (2020)."},{"key":"36244_CR14","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s00431-016-2712-z","volume":"175","author":"K De Boeck","year":"2016","unstructured":"De Boeck, K., Bulteel, V. & Fajac, I. Disease-specific clinical trials networks: the example of cystic fibrosis. Eur. J. Pediatr. 175, 817\u2013824 (2016).","journal-title":"Eur. J. Pediatr."},{"key":"36244_CR15","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.jcf.2016.05.007","volume":"15","author":"LV Silva Filho","year":"2016","unstructured":"Silva Filho, L. V., Castanos, C. & Ruiz, H. H. Cystic fibrosis in Latin America-Improving the awareness. J. Cyst. Fibros. 15, 791\u2013793 (2016).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR16","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.jcf.2017.11.019","volume":"17","author":"RH Keogh","year":"2018","unstructured":"Keogh, R. H., Szczesniak, R., Taylor-Robinson, D. & Bilton, D. Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data. J. Cyst. Fibros. 17, 218\u2013227 (2018).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR17","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1091\/mbc.e14-04-0935","volume":"27","author":"G Veit","year":"2016","unstructured":"Veit, G. et al. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol. Biol. Cell 27, 424\u2013433 (2016).","journal-title":"Mol. Biol. Cell"},{"key":"36244_CR18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s00018-016-2386-8","volume":"74","author":"X Meng","year":"2017","unstructured":"Meng, X., Clews, J., Kargas, V., Wang, X. & Ford, R. C. The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability. Cell Mol. Life Sci. 74, 23\u201338 (2017).","journal-title":"Cell Mol. Life Sci."},{"key":"36244_CR19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/0092-8674(95)90240-6","volume":"83","author":"CL Ward","year":"1995","unstructured":"Ward, C. L., Omura, S. & Kopito, R. R. Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83, 121\u2013127 (1995).","journal-title":"Cell"},{"key":"36244_CR20","doi-asserted-by":"publisher","first-page":"18825","DOI":"10.1073\/pnas.0904709106","volume":"106","author":"F Van Goor","year":"2009","unstructured":"Van Goor, F. et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc. Natl Acad. Sci. USA 106, 18825\u201318830 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"36244_CR21","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","volume":"365","author":"BW Ramsey","year":"2011","unstructured":"Ramsey, B. W. et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N. Engl. J. Med. 365, 1663\u20131672 (2011).","journal-title":"N. Engl. J. Med."},{"key":"36244_CR22","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1056\/NEJMoa1409547","volume":"373","author":"CE Wainwright","year":"2015","unstructured":"Wainwright, C. E. et al. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N. Engl. J. Med. 373, 220\u2013231 (2015).","journal-title":"N. Engl. J. Med."},{"key":"36244_CR23","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1164\/rccm.201704-0717OC","volume":"197","author":"SH Donaldson","year":"2018","unstructured":"Donaldson, S. H. et al. Tezacaftor\/Ivacaftor in Subjects with Cystic Fibrosis and F508del\/F508del-CFTR or F508del\/G551D-CFTR. Am. J. Respir. Crit. Care Med. 197, 214\u2013224 (2018).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"36244_CR24","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1056\/NEJMoa1807120","volume":"379","author":"D Keating","year":"2018","unstructured":"Keating, D. et al. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N. Engl. J. Med. 379, 1612\u20131620 (2018).","journal-title":"N. Engl. J. Med."},{"key":"36244_CR25","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","volume":"381","author":"PG Middleton","year":"2019","unstructured":"Middleton, P. G. et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N. Engl. J. Med. 381, 1809\u20131819 (2019).","journal-title":"N. Engl. J. Med."},{"key":"36244_CR26","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","volume":"394","author":"HGM Heijerman","year":"2019","unstructured":"Heijerman, H. G. M. et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet 394, 1940\u20131948 (2019).","journal-title":"Lancet"},{"key":"36244_CR27","unstructured":"Agency, E. M. Qualification Opinion on The European Cystic Fibrosis Society Patient Registry (ECFSPR) and CF Pharmaco-epidemiology Studies, https:\/\/www.ema.europa.eu\/en\/documents\/regulatory-procedural-guideline\/qualification-opinion-european-cystic-fibrosis-society-patient-registry-ecfspr-cf-pharmaco_en.pdf (2018)."},{"key":"36244_CR28","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1164\/rccm.202108-1986OC","volume":"205","author":"DP Nichols","year":"2022","unstructured":"Nichols, D. P. et al. Clinical effectiveness of elexacaftor\/tezacaftor\/ivacaftor in people with cystic fibrosis: a clinical trial. Am. J. Respir. Crit. Care Med. 205, 529\u2013539 (2022).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"36244_CR29","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s41669-019-0144-1","volume":"4","author":"B Mohindru","year":"2020","unstructured":"Mohindru, B. et al. Health state utility data in cystic fibrosis: a systematic review. Pharmacoecon. Open 4, 13\u201325 (2020).","journal-title":"Pharmacoecon. Open"},{"key":"36244_CR30","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1080\/14656566.2017.1359255","volume":"18","author":"N Zainal Abidin","year":"2017","unstructured":"Zainal Abidin, N., Haq, I. J., Gardner, A. I. & Brodlie, M. Ataluren in cystic fibrosis: development, clinical studies and where are we now. Expert Opin. Pharmacother. 18, 1363\u20131371 (2017).","journal-title":"Expert Opin. Pharmacother."},{"key":"36244_CR31","doi-asserted-by":"crossref","unstructured":"Konstan, M. W. et al. Efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis not receiving chronic inhaled aminoglycosides: The international, randomized, double-blind, placebo-controlled Ataluren Confirmatory Trial in Cystic Fibrosis (ACT CF. J. Cyst. Fibros. 19, 595\u2013601 (2020).","DOI":"10.1016\/j.jcf.2020.01.007"},{"key":"36244_CR32","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1002\/acn3.51149","volume":"7","author":"C Pascual-Morena","year":"2020","unstructured":"Pascual-Morena, C. et al. Restorative treatments of dystrophin expression in Duchenne muscular dystrophy: a systematic review. Ann. Clin. Transl. Neurol. 7, 1738\u20131752 (2020).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"36244_CR33","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.jcf.2021.01.009","volume":"20","author":"DK Crawford","year":"2021","unstructured":"Crawford, D. K. et al. Targeting G542X CFTR nonsense alleles with ELX-02 restores CFTR function in human-derived intestinal organoids. J. Cyst. Fibros. 20, 436\u2013442 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR34","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1177\/2472630317692561","volume":"22","author":"F Liang","year":"2017","unstructured":"Liang, F. et al. High-throughput screening for readthrough modulators of CFTR PTC mutations. SLAS Technol. 22, 315\u2013324 (2017).","journal-title":"SLAS Technol."},{"key":"36244_CR35","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.omtn.2022.04.033","volume":"28","author":"W Ko","year":"2022","unstructured":"Ko, W., Porter, J. J., Sipple, M. T., Edwards, K. M. & Lueck, J. D. Efficient suppression of endogenous CFTR nonsense mutations using anticodon-engineered transfer RNAs. Mol. Ther. Nucleic acids 28, 685\u2013701 (2022).","journal-title":"Mol. Ther. Nucleic acids"},{"key":"36244_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30668-y","volume":"13","author":"YJ Kim","year":"2022","unstructured":"Kim, Y. J. et al. Gene-specific nonsense-mediated mRNA decay targeting for cystic fibrosis therapy. Nat. Commun. 13, 2978 (2022).","journal-title":"Nat. Commun."},{"key":"36244_CR37","doi-asserted-by":"publisher","first-page":"e0219182","DOI":"10.1371\/journal.pone.0219182","volume":"14","author":"W Beumer","year":"2019","unstructured":"Beumer, W. et al. Evaluation of eluforsen, a novel RNA oligonucleotide for restoration of CFTR function in in vitro and murine models of p.Phe508del cystic fibrosis. PloS one 14, e0219182 (2019).","journal-title":"PloS one"},{"key":"36244_CR38","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.jcf.2018.10.015","volume":"18","author":"I Sermet-Gaudelus","year":"2019","unstructured":"Sermet-Gaudelus, I. et al. Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis. J. Cyst. Fibros. 18, 536\u2013542 (2019).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR39","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/j.jcf.2021.06.003","volume":"20","author":"YS Oren","year":"2021","unstructured":"Oren, Y. S. et al. Antisense oligonucleotide-based drug development for Cystic Fibrosis patients carrying the 3849+10 kb C-to-T splicing mutation. J. Cyst. Fibros. 20, 865\u2013875 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR40","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1002\/ppul.23543","volume":"51","author":"EW Alton","year":"2016","unstructured":"Alton, E. W. et al. Genetic medicines for CF: Hype versus reality. Pediatr. Pulmonol. 51, S5\u2013S17 (2016).","journal-title":"Pediatr. Pulmonol."},{"key":"36244_CR41","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/S2213-2600(15)00245-3","volume":"3","author":"EW Alton","year":"2015","unstructured":"Alton, E. W. et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir. Med. 3, 684\u2013691 (2015).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR42","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1136\/thoraxjnl-2016-208406","volume":"72","author":"EW Alton","year":"2017","unstructured":"Alton, E. W. et al. Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis. Thorax 72, 137\u2013147 (2017).","journal-title":"Thorax"},{"key":"36244_CR43","doi-asserted-by":"publisher","first-page":"576293","DOI":"10.3389\/fphar.2020.576293","volume":"11","author":"L Perrem","year":"2020","unstructured":"Perrem, L. & Ratjen, F. Designing clinical trials for anti-inflammatory therapies in cystic fibrosis. Front Pharm. 11, 576293 (2020).","journal-title":"Front Pharm."},{"key":"36244_CR44","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.3389\/fphar.2020.01290","volume":"11","author":"M Briottet","year":"2020","unstructured":"Briottet, M., Shum, M. & Urbach, V. The role of specialized pro-resolving mediators in cystic fibrosis airways disease. Front Pharm. 11, 1290 (2020).","journal-title":"Front Pharm."},{"key":"36244_CR45","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.jcf.2020.12.015","volume":"20","author":"LW Garratt","year":"2021","unstructured":"Garratt, L. W. et al. Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis. J. Cyst. Fibros. 20, 941\u2013948 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR46","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1513\/AnnalsATS.201907-493OC","volume":"17","author":"JK Harris","year":"2020","unstructured":"Harris, J. K. et al. Changes in airway microbiome and inflammation with ivacaftor treatment in patients with cystic fibrosis and the g551d mutation. Ann. Am. Thorac. Soc. 17, 212\u2013220 (2020).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"36244_CR47","doi-asserted-by":"publisher","first-page":"S30","DOI":"10.1002\/ppul.24129","volume":"53","author":"EA Roesch","year":"2018","unstructured":"Roesch, E. A., Nichols, D. P. & Chmiel, J. F. Inflammation in cystic fibrosis: an update. Pediatr. Pulmonol. 53, S30\u2013S50 (2018).","journal-title":"Pediatr. Pulmonol."},{"key":"36244_CR48","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jcf.2013.12.009","volume":"13","author":"MW Konstan","year":"2014","unstructured":"Konstan, M. W. et al. A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis. J. Cyst. Fibros. 13, 148\u2013155 (2014).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR49","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/cts.12428","volume":"10","author":"JS Elborn","year":"2017","unstructured":"Elborn, J. S. et al. Phase I studies of acebilustat: biomarker response and safety in patients with cystic fibrosis. Clin. Transl. Sci. 10, 28\u201334 (2017).","journal-title":"Clin. Transl. Sci."},{"key":"36244_CR50","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.jcf.2021.08.007","volume":"20","author":"JS Elborn","year":"2021","unstructured":"Elborn, J. S. et al. Empire-CF study: A phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis. J. Cyst. Fibros. 20, 1026\u20131034 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR51","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s00296-007-0489-0","volume":"28","author":"J Parker","year":"2008","unstructured":"Parker, J. et al. Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid. Rheumatol. Int 28, 631\u2013635 (2008).","journal-title":"Rheumatol. Int"},{"key":"36244_CR52","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jcf.2020.09.008","volume":"20","author":"JF Chmiel","year":"2021","unstructured":"Chmiel, J. F. et al. Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis. J. Cyst. Fibros. 20, 78\u201385 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR53","doi-asserted-by":"publisher","first-page":"e1152","DOI":"10.1002\/cti2.1152","volume":"9","author":"A Lucas","year":"2020","unstructured":"Lucas, A., Yasa, J. & Lucas, M. Regeneration and repair in the healing lung. Clin. Transl. Immunol. 9, e1152 (2020).","journal-title":"Clin. Transl. Immunol."},{"key":"36244_CR54","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.stem.2017.03.024","volume":"21","author":"AJ Lechner","year":"2017","unstructured":"Lechner, A. J. et al. Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy. Cell Stem Cell 21, 120\u2013134.e127 (2017).","journal-title":"Cell Stem Cell"},{"key":"36244_CR55","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12861-015-0082-9","volume":"15","author":"ML Donne","year":"2015","unstructured":"Donne, M. L., Lechner, A. J. & Rock, J. R. Evidence for lung epithelial stem cell niches. BMC Dev. Biol. 15, 32 (2015).","journal-title":"BMC Dev. Biol."},{"key":"36244_CR56","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1164\/rccm.201308-1433IM","volume":"189","author":"S Hoare","year":"2014","unstructured":"Hoare, S. et al. Ivacaftor imaging response in cystic fibrosis. Am. J. Respir. Crit. Care Med. 189, 484 (2014).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"36244_CR57","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/ppul.24604","volume":"55","author":"SL Martiniano","year":"2020","unstructured":"Martiniano, S. L. et al. Challenging scenarios in nontuberculous mycobacterial infection in cystic fibrosis. Pediatr. Pulmonol. 55, 521\u2013525 (2020).","journal-title":"Pediatr. Pulmonol."},{"key":"36244_CR58","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.coph.2018.09.007","volume":"43","author":"RJ Shei","year":"2018","unstructured":"Shei, R. J., Peabody, J. E., Kaza, N. & Rowe, S. M. The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis. Curr. Opin. Pharmacol. 43, 152\u2013165 (2018).","journal-title":"Curr. Opin. Pharmacol."},{"key":"36244_CR59","doi-asserted-by":"publisher","unstructured":"Mall, M. A. ENaC inhibition in cystic fibrosis: potential role in the new era of CFTR modulator therapies. The European respiratory journal 56, https:\/\/doi.org\/10.1183\/13993003.00946-2020 (2020).","DOI":"10.1183\/13993003.00946-2020"},{"key":"36244_CR60","doi-asserted-by":"publisher","unstructured":"Danahay, H. & Gosling, M. TMEM16A: An alternative approach to restoring airway anion secretion in cystic fibrosis? Int. J. Mol. Sci. 21, https:\/\/doi.org\/10.3390\/ijms21072386 (2020).","DOI":"10.3390\/ijms21072386"},{"key":"36244_CR61","doi-asserted-by":"publisher","unstructured":"van Koningsbruggen-Rietschel, S. et al. Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study. ERJ Open Res 6, https:\/\/doi.org\/10.1183\/23120541.00132-2020 (2020).","DOI":"10.1183\/23120541.00132-2020"},{"key":"36244_CR62","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1111\/resp.13047","volume":"22","author":"BJ Tarrant","year":"2017","unstructured":"Tarrant, B. J. et al. Mucoactive agents for chronic, non-cystic fibrosis lung disease: a systematic review and meta-analysis. Respirology 22, 1084\u20131092 (2017).","journal-title":"Respirology"},{"key":"36244_CR63","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1016\/S0140-6736(09)62161-9","volume":"375","author":"J McCormick","year":"2010","unstructured":"McCormick, J. et al. Comparative demographics of the European cystic fibrosis population: a cross-sectional database analysis. Lancet 375, 1007\u20131013 (2010).","journal-title":"Lancet"},{"key":"36244_CR64","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1515\/jpem-2019-0484","volume":"33","author":"C Alves","year":"2020","unstructured":"Alves, C., Della-Manna, T. & Albuquerque, C. T. M. Cystic fibrosis-related diabetes: an update on pathophysiology, diagnosis, and treatment. J. Pediatr. Endocrinol. Metab. 33, 835\u2013843 (2020).","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"36244_CR65","doi-asserted-by":"publisher","first-page":"S56","DOI":"10.1016\/j.jcf.2019.08.017","volume":"18","author":"MS Putman","year":"2019","unstructured":"Putman, M. S., Anabtawi, A., Le, T., Tangpricha, V. & Sermet-Gaudelus, I. Cystic fibrosis bone disease treatment: current knowledge and future directions. J. Cyst. Fibros. 18, S56\u2013S65 (2019).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR66","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/S1470-2045(18)30188-8","volume":"19","author":"A Yamada","year":"2018","unstructured":"Yamada, A. et al. Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis. Lancet Oncol. 19, 758\u2013767 (2018).","journal-title":"Lancet Oncol."},{"key":"36244_CR67","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1053\/j.gastro.2017.12.012","volume":"154","author":"D Hadjiliadis","year":"2018","unstructured":"Hadjiliadis, D. et al. Cystic fibrosis colorectal cancer screening consensus recommendations. Gastroenterology 154, 736\u2013745 e714 (2018).","journal-title":"Gastroenterology"},{"key":"36244_CR68","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1016\/S0140-6736(20)32542-3","volume":"397","author":"M Shteinberg","year":"2021","unstructured":"Shteinberg, M., Haq, I. J., Polineni, D. & Davies, J. C. Cystic fibrosis. Lancet 397, 2195\u20132211 (2021).","journal-title":"Lancet"},{"key":"36244_CR69","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.jcf.2020.09.002","volume":"20","author":"M Cohen-Cymberknoh","year":"2021","unstructured":"Cohen-Cymberknoh, M. et al. Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression. J. Cyst. Fibros. 20, 388\u2013394 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR70","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.jcf.2019.05.015","volume":"19","author":"N Volkova","year":"2020","unstructured":"Volkova, N. et al. Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries. J. Cyst. Fibros. 19, 68\u201379 (2020).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR71","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1164\/rccm.201609-1954OC","volume":"195","author":"KB Hisert","year":"2017","unstructured":"Hisert, K. B. et al. Restoring cystic fibrosis transmembrane conductance regulator function reduces airway bacteria and inflammation in people with cystic fibrosis and chronic lung infections. Am. J. Respir. Crit. Care Med. 195, 1617\u20131628 (2017).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"36244_CR72","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1136\/thoraxjnl-2013-204176","volume":"69","author":"LP Thia","year":"2014","unstructured":"Thia, L. P. et al. Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of age? Thorax 69, 320\u2013327 (2014).","journal-title":"Thorax"},{"key":"36244_CR73","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1164\/rccm.200911-1646OC","volume":"183","author":"P Aurora","year":"2011","unstructured":"Aurora, P. et al. Lung clearance index at 4 years predicts subsequent lung function in children with cystic fibrosis. Am. J. respiratory Crit. care Med. 183, 752\u2013758 (2011).","journal-title":"Am. J. respiratory Crit. care Med."},{"key":"36244_CR74","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1164\/rccm.201407-1277OC","volume":"190","author":"KA Ramsey","year":"2014","unstructured":"Ramsey, K. A. et al. Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis. Am. J. respiratory Crit. care Med. 190, 1111\u20131116 (2014).","journal-title":"Am. J. respiratory Crit. care Med."},{"key":"36244_CR75","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1056\/NEJMoa1301725","volume":"368","author":"PD Sly","year":"2013","unstructured":"Sly, P. D. et al. Risk factors for bronchiectasis in children with cystic fibrosis. N. Engl. J. Med. 368, 1963\u20131970 (2013).","journal-title":"N. Engl. J. Med."},{"key":"36244_CR76","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1002\/(SICI)1099-0496(199911)28:5<321::AID-PPUL3>3.0.CO;2-V","volume":"28","author":"M Rosenfeld","year":"1999","unstructured":"Rosenfeld, M. et al. Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatr. Pulmonol. 28, 321\u2013328 (1999).","journal-title":"Pediatr. Pulmonol."},{"key":"36244_CR77","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/S2213-2600(18)30171-1","volume":"6","author":"K Ronchetti","year":"2018","unstructured":"Ronchetti, K. et al. The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial. Lancet Respir. Med. 6, 461\u2013471 (2018).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR78","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.jcf.2016.01.001","volume":"15","author":"M Zampoli","year":"2016","unstructured":"Zampoli, M., Pillay, K., Carrara, H., Zar, H. J. & Morrow, B. Microbiological yield from induced sputum compared to oropharyngeal swab in young children with cystic fibrosis. J. Cyst. Fibros. 15, 605\u2013610 (2016).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR79","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s00408-017-0008-3","volume":"195","author":"ACM Ferreira","year":"2017","unstructured":"Ferreira, A. C. M. et al. Hypertonic saline as a useful tool for sputum induction and pathogen detection in cystic fibrosis. Lung 195, 431\u2013439 (2017).","journal-title":"Lung"},{"key":"36244_CR80","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1002\/ppul.24366","volume":"54","author":"S Shanthikumar","year":"2019","unstructured":"Shanthikumar, S., Neeland, M. N., Saffery, R. & Ranganathan, S. Gene modifiers of cystic fibrosis lung disease: A systematic review. Pediatr. Pulmonol. 54, 1356\u20131366 (2019).","journal-title":"Pediatr. Pulmonol."},{"key":"36244_CR81","doi-asserted-by":"publisher","first-page":"e0239189","DOI":"10.1371\/journal.pone.0239189","volume":"15","author":"H Dang","year":"2020","unstructured":"Dang, H. et al. Mining GWAS and eQTL data for CF lung disease modifiers by gene expression imputation. PloS one 15, e0239189 (2020).","journal-title":"PloS one"},{"key":"36244_CR82","doi-asserted-by":"publisher","unstructured":"Kopp, B. T. et al. The impact of secondhand smoke exposure on children with cystic fibrosis: a review. Int. J. Environ. Res. Public Health 13, https:\/\/doi.org\/10.3390\/ijerph13101003 (2016).","DOI":"10.3390\/ijerph13101003"},{"key":"36244_CR83","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/ppul.10127","volume":"34","author":"J Emerson","year":"2002","unstructured":"Emerson, J., Rosenfeld, M., McNamara, S., Ramsey, B. & Gibson, R. L. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr. Pulmonol. 34, 91\u2013100 (2002).","journal-title":"Pediatr. Pulmonol."},{"key":"36244_CR84","doi-asserted-by":"publisher","unstructured":"Baker, E., Harris, W. T., Rowe, S. M., Rutland, S. B. & Oates, G. R. Tobacco smoke exposure limits the therapeutic benefit of tezacaftor\/ivacaftor in pediatric patients with cystic fibrosis. J. Cyst. Fibros., https:\/\/doi.org\/10.1016\/j.jcf.2020.09.011 (2020).","DOI":"10.1016\/j.jcf.2020.09.011"},{"key":"36244_CR85","doi-asserted-by":"publisher","first-page":"e0127742","DOI":"10.1371\/journal.pone.0127742","volume":"10","author":"BA Stanton","year":"2015","unstructured":"Stanton, B. A., Coutermarsh, B., Barnaby, R. & Hogan, D. Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells. PloS one 10, e0127742 (2015).","journal-title":"PloS one"},{"key":"36244_CR86","doi-asserted-by":"publisher","unstructured":"Sakon, C. et al. Opportunity for pharmacogenomic testing in patients with cystic fibrosis. Pediatric pulmonology, https:\/\/doi.org\/10.1002\/ppul.25809 (2021).","DOI":"10.1002\/ppul.25809"},{"key":"36244_CR87","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1080\/21556660.2021.1912352","volume":"10","author":"Z Mehta","year":"2021","unstructured":"Mehta, Z., Kamal, K. M., Miller, R., Covvey, J. R. & Giannetti, V. Adherence to cystic fibrosis transmembrane conductance regulator (CFTR) modulators: analysis of a national specialty pharmacy database. J. Drug Assess. 10, 62\u201367 (2021).","journal-title":"J. Drug Assess."},{"key":"36244_CR88","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1136\/thoraxjnl-2020-215556","volume":"76","author":"RM Mitchell","year":"2021","unstructured":"Mitchell, R. M., Jones, A. M., Stocking, K., Foden, P. & Barry, P. J. Longitudinal effects of ivacaftor and medicine possession ratio in people with the Gly551Asp mutation: a 5-year study. Thorax 76, 874\u2013879 (2021).","journal-title":"Thorax"},{"key":"36244_CR89","doi-asserted-by":"publisher","unstructured":"Mikulski, B. S., Bellei, E. A., Biduski, D. & De Marchi, A. C. B. Mobile Health Applications and Medication Adherence of Patients With Hypertension: A Systematic Review and Meta-Analysis. Am. J. Prev. Med. https:\/\/doi.org\/10.1016\/j.amepre.2021.11.003 (2021).","DOI":"10.1016\/j.amepre.2021.11.003"},{"key":"36244_CR90","doi-asserted-by":"publisher","unstructured":"Blakey, J. D. et al. Digital technologies and adherence in respiratory diseases: the road ahead. The European respiratory journal 52, https:\/\/doi.org\/10.1183\/13993003.01147-2018 (2018).","DOI":"10.1183\/13993003.01147-2018"},{"key":"36244_CR91","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.psym.2017.04.001","volume":"58","author":"JS Talwalkar","year":"2017","unstructured":"Talwalkar, J. S. et al. Cystic fibrosis transmembrane regulator modulators: implications for the management of depression and anxiety in cystic fibrosis. Psychosomatics 58, 343\u2013354 (2017).","journal-title":"Psychosomatics"},{"key":"36244_CR92","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.jcf.2020.07.017","volume":"20","author":"S Stanojevic","year":"2021","unstructured":"Stanojevic, S. et al. Projecting the impact of delayed access to elexacaftor\/tezacaftor\/ivacaftor for people with Cystic Fibrosis. J. Cyst. Fibros. 20, 243\u2013249 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR93","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.stem.2013.11.002","volume":"13","author":"G Schwank","year":"2013","unstructured":"Schwank, G. et al. Functional repair of CFTR by CRISPR\/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13, 653\u2013658 (2013).","journal-title":"Cell Stem Cell"},{"key":"36244_CR94","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.stem.2020.01.019","volume":"26","author":"MH Geurts","year":"2020","unstructured":"Geurts, M. H. et al. CRISPR-based adenine editors correct nonsense mutations in a cystic fibrosis organoid biobank. Cell Stem Cell 26, 503\u2013510 (2020).","journal-title":"Cell Stem Cell"},{"key":"36244_CR95","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1016\/j.ymthe.2020.04.021","volume":"28","author":"S Suzuki","year":"2020","unstructured":"Suzuki, S. et al. Highly efficient gene editing of cystic fibrosis patient-derived airway basal cells results in functional CFTR correction. Mol. Ther.: J. Am. Soc. Gene Ther. 28, 1684\u20131695 (2020).","journal-title":"Mol. Ther.: J. Am. Soc. Gene Ther."},{"key":"36244_CR96","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1136\/thoraxjnl-2017-210473","volume":"73","author":"NJ Rowbotham","year":"2018","unstructured":"Rowbotham, N. J. et al. The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers. Thorax 73, 388\u2013390 (2018).","journal-title":"Thorax"},{"key":"36244_CR97","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.jcf.2019.11.007","volume":"19","author":"AH Gifford","year":"2020","unstructured":"Gifford, A. H., Mayer-Hamblett, N., Pearson, K. & Nichols, D. P. Answering the call to address cystic fibrosis treatment burden in the era of highly effective CFTR modulator therapy. J. Cyst. Fibros. 19, 762\u2013767 (2020).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR98","doi-asserted-by":"publisher","unstructured":"Mayer-Hamblett, N. et al. Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials. The Lancet. Respir. Med. https:\/\/doi.org\/10.1016\/S2213-2600(22)00434-9 (2022).","DOI":"10.1016\/S2213-2600(22)00434-9"},{"key":"36244_CR99","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.jcf.2019.10.025","volume":"19","author":"G Davies","year":"2020","unstructured":"Davies, G. et al. Characterising burden of treatment in cystic fibrosis to identify priority areas for clinical trials. J. Cyst. Fibros. 19, 499\u2013502 (2020).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR100","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.jcf.2019.06.011","volume":"18","author":"JC Davies","year":"2019","unstructured":"Davies, J. C. et al. Speeding up access to new drugs for CF: considerations for clinical trial design and delivery. J. Cyst. Fibros. 18, 677\u2013684 (2019).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR101","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.jcf.2019.06.010","volume":"18","author":"MD Amaral","year":"2019","unstructured":"Amaral, M. D. et al. Theranostics by testing CFTR modulators in patient-derived materials: the current status and a proposal for subjects with rare CFTR mutations. J. Cyst. Fibros. 18, 685\u2013692 (2019).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR102","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.jcf.2020.05.012","volume":"19","author":"K De Boeck","year":"2020","unstructured":"De Boeck, K. et al. Cystic fibrosis drug trial design in the era of CFTR modulators associated with substantial clinical benefit: stakeholders\u2019 consensus view. J. Cyst. Fibros. 19, 688\u2013695 (2020).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR103","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nrg3849","volume":"16","author":"GR Cutting","year":"2015","unstructured":"Cutting, G. R. Cystic fibrosis genetics: from molecular understanding to clinical application. Nat. Rev. Genet 16, 45\u201356 (2015).","journal-title":"Nat. Rev. Genet"},{"key":"36244_CR104","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jcf.2018.05.004","volume":"18","author":"JP Clancy","year":"2019","unstructured":"Clancy, J. P. et al. CFTR modulator theratyping: Current status, gaps and future directions. J. Cyst. Fibros. 18, 22\u201334 (2019).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR105","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1097\/MCP.0000000000000315","volume":"22","author":"J Noordhoek","year":"2016","unstructured":"Noordhoek, J., Gulmans, V., van der Ent, K. & Beekman, J. M. Intestinal organoids and personalized medicine in cystic fibrosis: a successful patient-oriented research collaboration. Curr. Opin. Pulm. Med. 22, 610\u2013616 (2016).","journal-title":"Curr. Opin. Pulm. Med."},{"key":"36244_CR106","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.jcf.2020.05.011","volume":"19","author":"N Mayer-Hamblett","year":"2020","unstructured":"Mayer-Hamblett, N. et al. Building global development strategies for cf therapeutics during a transitional cftr modulator era. J. Cyst. Fibros. 19, 677\u2013687 (2020).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR107","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.jcf.2021.03.027","volume":"20","author":"R Dobra","year":"2021","unstructured":"Dobra, R. et al. Optimising equity of access: how should we allocate slots to the most competitive trials in Cystic Fibrosis (CF). J. Cyst. Fibros. 20, 978\u2013985 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR108","doi-asserted-by":"publisher","first-page":"R95","DOI":"10.1093\/hmg\/ddz157","volume":"28","author":"P Batty","year":"2019","unstructured":"Batty, P. & Lillicrap, D. Advances and challenges for hemophilia gene therapy. Hum. Mol. Genet 28, R95\u2013R101 (2019).","journal-title":"Hum. Mol. Genet"},{"key":"36244_CR109","first-page":"379","volume":"15","author":"E Masat","year":"2013","unstructured":"Masat, E., Pavani, G. & Mingozzi, F. Humoral immunity to AAV vectors in gene therapy: challenges and potential solutions. Disco. Med 15, 379\u2013389 (2013).","journal-title":"Disco. Med"},{"key":"36244_CR110","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1056\/NEJMoa0909825","volume":"363","author":"FJ Accurso","year":"2010","unstructured":"Accurso, F. J. et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N. Engl. J. Med. 363, 1991\u20132003 (2010).","journal-title":"N. Engl. J. Med."},{"key":"36244_CR111","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.jcf.2021.02.003","volume":"20","author":"DP Nichols","year":"2021","unstructured":"Nichols, D. P. et al. PROMISE: working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy. J. Cyst. Fibros. 20, 205\u2013212 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR112","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/S2213-2600(15)00201-5","volume":"3","author":"RB Moss","year":"2015","unstructured":"Moss, R. B. et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir. Med. 3, 524\u2013533 (2015).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR113","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1097\/MCP.0000000000000732","volume":"26","author":"C Nissenbaum","year":"2020","unstructured":"Nissenbaum, C., Davies, G., Horsley, A. & Davies, J. C. Monitoring early stage lung disease in cystic fibrosis. Curr. Opin. Pulm. Med. 26, 671\u2013678 (2020).","journal-title":"Curr. Opin. Pulm. Med."},{"key":"36244_CR114","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.jcf.2020.07.023","volume":"20","author":"JC Davies","year":"2021","unstructured":"Davies, J. C. et al. A phase 3, double-blind, parallel-group study to evaluate the efficacy and safety of tezacaftor in combination with ivacaftor in participants 6 through 11 years of age with cystic fibrosis homozygous for F508del or heterozygous for the F508del-CFTR mutation and a residual function mutation. J. Cyst. Fibros. 20, 68\u201377 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR115","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1080\/17476348.2021.1908131","volume":"15","author":"P Mondejar-Lopez","year":"2021","unstructured":"Mondejar-Lopez, P. et al. A multimodal approach to detect and monitor early lung disease in cystic fibrosis. Expert Rev. Respir. Med 15, 761\u2013772 (2021).","journal-title":"Expert Rev. Respir. Med"},{"key":"36244_CR116","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1136\/thoraxjnl-2016-208948","volume":"72","author":"H Marshall","year":"2017","unstructured":"Marshall, H. et al. Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI. Thorax 72, 760\u2013762 (2017).","journal-title":"Thorax"},{"key":"36244_CR117","doi-asserted-by":"publisher","first-page":"4037","DOI":"10.1007\/s00330-018-5383-5","volume":"28","author":"K Martini","year":"2018","unstructured":"Martini, K. et al. Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients. Eur. Radio. 28, 4037\u20134047 (2018).","journal-title":"Eur. Radio."},{"key":"36244_CR118","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.jcf.2017.02.012","volume":"16","author":"DR VanDevanter","year":"2017","unstructured":"VanDevanter, D. R., Mayer-Hamblett, N. & Boyle, M. Feasibility of placebo-controlled trial designs for new CFTR modulator evaluation. J. Cyst. Fibros. 16, 496\u2013498 (2017).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR119","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1016\/j.jcf.2017.09.006","volume":"17","author":"AT Trimble","year":"2018","unstructured":"Trimble, A. T. & Donaldson, S. H. Ivacaftor withdrawal syndrome in cystic fibrosis patients with the G551D mutation. J. Cyst. Fibros. 17, e13\u2013e16 (2018).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR120","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S2213-2600(15)00545-7","volume":"4","author":"JC Davies","year":"2016","unstructured":"Davies, J. C. et al. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir. Med. 4, 107\u2013115 (2016).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR121","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S2213-2600(18)30202-9","volume":"6","author":"M Rosenfeld","year":"2018","unstructured":"Rosenfeld, M. et al. Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study. Lancet Respir. Med. 6, 545\u2013553 (2018).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR122","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jcf.2020.08.019","volume":"20","author":"M Lee","year":"2021","unstructured":"Lee, M. et al. Factors influencing clinical trial participation for adult and pediatric patients with cystic fibrosis. J. Cyst. Fibros. 20, 57\u201360 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR123","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.jcf.2021.03.021","volume":"20","author":"R Dobra","year":"2021","unstructured":"Dobra, R. et al. Guiding the rational design of patient-centred drug trials in Cystic Fibrosis: a Delphi study. J. Cyst. Fibros. 20, 986\u2013993 (2021).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR124","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-021-05457-5","volume":"22","author":"S van Koningsbruggen-Rietschel","year":"2021","unstructured":"van Koningsbruggen-Rietschel, S. et al. Protecting clinical trials in cystic fibrosis during the SARS-CoV-2 pandemic: risks and mitigation measures. Trials 22, 578 (2021).","journal-title":"Trials"},{"key":"36244_CR125","doi-asserted-by":"publisher","first-page":"e0160475","DOI":"10.1371\/journal.pone.0160475","volume":"11","author":"N Fudge","year":"2016","unstructured":"Fudge, N. et al. Optimising Translational Research Opportunities: a Systematic Review and Narrative Synthesis of Basic and Clinician Scientists\u2019 Perspectives of Factors Which Enable or Hinder Translational Research. PloS one 11, e0160475 (2016).","journal-title":"PloS one"},{"key":"36244_CR126","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1136\/thoraxjnl-2017-210394","volume":"73","author":"L Bessonova","year":"2018","unstructured":"Bessonova, L. et al. Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor. Thorax 73, 731\u2013740 (2018).","journal-title":"Thorax"},{"key":"36244_CR127","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","volume":"8","author":"SC Bell","year":"2020","unstructured":"Bell, S. C. et al. The future of cystic fibrosis care: a global perspective. Lancet Respir. Med. 8, 65\u2013124 (2020).","journal-title":"Lancet Respir. Med."},{"key":"36244_CR128","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s40272-022-00509-y","volume":"24","author":"JA King","year":"2022","unstructured":"King, J. A., Nichols, A. L., Bentley, S., Carr, S. B. & Davies, J. C. An Update on CFTR Modulators as New Therapies for Cystic Fibrosis. Paediatr. drugs 24, 321\u2013333 (2022).","journal-title":"Paediatr. drugs"},{"key":"36244_CR129","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.1016\/j.jcf.2019.12.012","volume":"19","author":"A Christopher Boyd","year":"2020","unstructured":"Christopher Boyd, A. et al. New approaches to genetic therapies for cystic fibrosis. J. Cyst. Fibros. 19, S54\u2013S59 (2020).","journal-title":"J. Cyst. Fibros."},{"key":"36244_CR130","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1097\/MCP.0000000000000827","volume":"27","author":"I Fajac","year":"2021","unstructured":"Fajac, I. & Sermet-Gaudelus, I. Therapeutic pipeline for individuals with cystic fibrosis with mutations nonresponsive to current cystic fibrosis transmembrane conductance regulator modulators. Curr. Opin. Pulm. Med. 27, 567\u2013574 (2021).","journal-title":"Curr. Opin. Pulm. Med."},{"key":"36244_CR131","doi-asserted-by":"publisher","first-page":"102206","DOI":"10.1016\/j.coph.2022.102206","volume":"64","author":"LJV Galietta","year":"2022","unstructured":"Galietta, L. J. V. TMEM16A (ANO1) as a therapeutic target in cystic fibrosis. Curr. Opin. Pharmacol. 64, 102206 (2022).","journal-title":"Curr. Opin. Pharmacol."},{"key":"36244_CR132","doi-asserted-by":"publisher","first-page":"102248","DOI":"10.1016\/j.coph.2022.102248","volume":"65","author":"MF Figueira","year":"2022","unstructured":"Figueira, M. F., Ribeiro, C. M. P. & Button, B. Mucus-targeting therapies of defective mucus clearance for cystic fibrosis: a short review. Curr. Opin. Pharmacol. 65, 102248 (2022).","journal-title":"Curr. Opin. Pharmacol."},{"key":"36244_CR133","doi-asserted-by":"publisher","unstructured":"Manos, J. Current and emerging therapies to combat cystic fibrosis lung infections. Microorganisms 9, https:\/\/doi.org\/10.3390\/microorganisms9091874 (2021).","DOI":"10.3390\/microorganisms9091874"},{"key":"36244_CR134","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/ppul.25459","volume":"57","author":"NJ Antos","year":"2022","unstructured":"Antos, N. J. & Savant, A. P. Cystic fibrosis year in review 2020: section 2 pulmonary disease, infections, and inflammation. Pediatr. Pulmonol. 57, 347\u2013360 (2022).","journal-title":"Pediatr. Pulmonol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-023-36244-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-023-36244-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-023-36244-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T06:06:56Z","timestamp":1676095616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-023-36244-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,8]]},"references-count":134,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["36244"],"URL":"https:\/\/doi.org\/10.1038\/s41467-023-36244-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,8]]},"assertion":[{"value":"7 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Lu. Allen, Lo. Allen, J.T.F., and K.W.S. declare no competing interests. S.B.C. has received grants from the NIHR and undertaking consultancy work for Vertex Pharmaceuticals and Chiesi. She has performed advisory roles for Profile Pharma, Pharmaxis and Vertex Pharmaceuticals. Siobhan is the chair of the UK CF registry steering committee and the European CF society patient registry scientific committee. G.D. has performed clinical trial leadership roles and received speaker honoraria from Vertex Pharmaceuticals, and speaker honoraria from Chiesi Ltd for educational events. She holds current grants from UKRI, NIHR and CF Trust. D.D. has received honoraria and\/or grants from, Vertex, Proteostasis, Chiesi, Gilead and Insmed. M.E. is a consultant for Xanadu Bio Sciences. R.G. has received speaker fees from Vertex and Chiesi and and provided consultancy work for Chiesi. C.H. has performed clinical trial leadership roles, and educational and\/or advisory activities for 30 Technology, Aradigm, Chiesi, CSL Behring, Gilead, Grifols, GSK, Insmed, Janssen, Meiji, Mylan, Novartis, Pneumagen, Shionogi, Teva, Vertex and Zambon. A.H. has performed clinical trial leadership roles, and educational or advisory activities for the following: Boehringer Ingelheim Pharma GmbH, Celtaxys Pharmaceuticals, Flatley Labs, Galapagos NV, Roche-Genentech, Krystal Biotech, Novabiotics, Pulmocide, Vertex Pharmaceuticals. He holds current grants from EPSRC, UKRI, CF Trust, JP Moulton charity, North West Lung Centre Charity. A.R.S. has received research grants; honoraria for lectures; and support for attending meetings from Vertex Pharmaceuticals (all outside the submitted work). A.R.S. has patents issued (Camara M, Williams P, Barrett D, Halliday N, Knox A, Smyth A, Fogarty A, Barr H, Forrester D. Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof (), outside the submitted work. J.C.D. has performed clinical trial leadership roles, and educational and\/or advisory activities for the following: Abbvie, Algipharma AS, Bayer AG, Boehringer Ingelheim Pharma GmbH & Co. KG, Eloxx, Enterprise, Galapagos NV, Genentech, ImevaX GmbH, Ionis, LifeArc, Nivalis Therapeutics, Inc., Krystal Biotech, Novartis, PARI Medical Holding GmbH, ProQR Therapeutics III B.V., Proteostasis Therapeutics INC., Pulmocide, Raptor Pharmaceuticals Inc, Recode, Vertex Pharmaceuticals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"693"}}