{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:01:26Z","timestamp":1785290486486,"version":"3.55.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Since the introduction of CFTR modulator therapies, longitudinal real-life data of lung clearance index (LCI) during treatment is scarce. In this single-centre, post-approval setting, we report data of 51 patients with different stages of lung disease, age 2\u201352\u00a0years with repeated measurements of forced expiratory volume as a percentage of the predicted value (ppFEV\u2081) and LCI after 2, 4, and 16\u00a0weeks of CFTR modulator treatment and at baseline. In 25 patients during elexacaftor\/tezacaftor\/ivacaftor (ELX\/TEZ\/IVA) treatment, significant improvements of LCI (median \u22121.4) and ppFEV\u2081 (median +8.3%) were observed after only 2\u00a0weeks, and were maintained after 4 and 16\u00a0weeks of treatment (LCI: -2.0, \u22122.2; ppFEV\u2081: +7.2%, +11.8%). We observed a significant correlation between LCI improvement at week 16 and lower baseline LCI. In 26 younger and healthier patients receiving lumacaftor\/ivacaftor (LUM\/IVA) treatment, no significant changes of LCI and ppFEV\u2081 occured. With ELX\/TEZ\/IVA, our data shows rapid, significant improvements of LCI and ppFEV\u2081 already after 2\u00a0weeks. Early LCI measurements can help to assess the patient\u2019s response to this high-cost therapy.<\/jats:p>","DOI":"10.3389\/fphar.2023.1125853","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T05:22:26Z","timestamp":1678252946000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Early and sustained improvements of lung clearance index from two to sixteen weeks of elexacaftor\/tezacaftor\/ivacaftor therapy in patients with cystic fibrosis\u2014a real world study"],"prefix":"10.3389","volume":"14","author":[{"given":"Dorothea","family":"Appelt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gratiana","family":"Steinkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Ellemunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1016\/j.rmed.2010.06.010","article-title":"Sensitivity of Lung Clearance Index and chest computed tomography in early CF lung disease","volume":"104","author":"Ellemunter","year":"2010","journal-title":"Respir. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1002\/ppul.21093","article-title":"Lung clearance index: Normal values, repeatability, and reproducibility in healthy children and adolescents","volume":"44","author":"Fuchs","year":"2009","journal-title":"Pediatr. Pulmonol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1513\/AnnalsATS.202008-1054OC","article-title":"Effects of Lumacaftor-Ivacaftor on Lung Clearance Index, Magnetic Resonance Imaging, and Airway Microbiome in Phe508del Homozygous Patients with Cystic Fibrosis","volume":"18","author":"Graeber","year":"2021","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B4","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1164\/rccm.202201-0219OC","article-title":"Effects of Elexacaftor\/Tezacaftor\/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles","volume":"206","author":"Graeber","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","article-title":"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","volume":"394","author":"Heijerman","year":"2019","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1164\/rccm.202202-0392OC","article-title":"Efficacy and Safety of Elexacaftor\/Tezacaftor\/Ivacaftor in Children 6 Through 11 Years of Age with Cystic Fibrosis Heterozygous for F508del and a Minimal Function Mutation: A Phase 3B, Randomized, Placebo-Controlled Study","volume":"206","author":"Mall","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1164\/rccm.201608-1754OC","article-title":"Lumacaftor\/ivacaftor in patients aged 6-11 Years with cystic fibrosis and homozygous for F508del-CFTR","volume":"195","author":"Milla","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1164\/rccm.202108-1986OC","article-title":"Clinical effectiveness of elexacaftor\/tezacaftor\/ivacaftor in people with cystic fibrosis: A clinical trial","volume":"205","author":"Nichols","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1101\/2022.01.27.22269250","article-title":"A non-systematic signal-correction error in a commercial multiple-breath washout device significantly impacts outcomes in children and adults","author":"Oestreich","year":"2022"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3-95-yr age range: The global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur. Respir. J."},{"key":"B12","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/S2213-2600(17)30215-1","article-title":"Efficacy and safety of lumacaftor and ivacaftor in patients aged 6\u201311 years with cystic fibrosis homozygous for F508del-CFTR: A randomised, placebo-controlled phase 3 trial","volume":"5","author":"Ratjen","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.jcf.2020.05.010","article-title":"Changes in LCI in F508del\/F508del patients treated with lumacaftor\/ivacaftor: Results from the prospect study","volume":"19","author":"Shaw","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"B14","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.jcf.2021.03.016","article-title":"Peripheral lung effect of elexacaftor\/tezacaftor\/ivacaftor in adult cystic fibrosis","volume":"21","author":"Stylemans","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"B15","first-page":"1148","article-title":"Correction of sensor crosstalk error in Exhalyzer D multiple-breath washout device significantly impacts outcomes in children with cystic fibrosis. J Appl Physiol","volume":"131","author":"Wyler","year":"2021","journal-title":"1985"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1164\/rccm.202102-0509OC","article-title":"A Phase 3 Open-Label Study of Elexacaftor\/Tezacaftor\/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele","volume":"203","author":"Zemanick","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1125853\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T05:22:30Z","timestamp":1678252950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1125853\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":16,"alternative-id":["10.3389\/fphar.2023.1125853"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1125853","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]},"article-number":"1125853"}}