{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:30:48Z","timestamp":1791095448079,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Independent medical grant from Vertex Pharmaceuticals Incorporated","award":["IIS-2018-107555"],"award-info":[{"award-number":["IIS-2018-107555"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL002A1"],"award-info":[{"award-number":["82DZL002A1"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL005B1"],"award-info":[{"award-number":["82DZL005B1"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL004B1"],"award-info":[{"award-number":["82DZL004B1"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1449-Z02 (431232613)"],"award-info":[{"award-number":["SFB 1449-Z02 (431232613)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Independent medical grant from Vertex Pharmaceuticals Incorporated","award":["IIS-2018-107555"],"award-info":[{"award-number":["IIS-2018-107555"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL002A1"],"award-info":[{"award-number":["82DZL002A1"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL005B1"],"award-info":[{"award-number":["82DZL005B1"]}]},{"name":"German Federal Ministry of Education and Research","award":["82DZL004B1"],"award-info":[{"award-number":["82DZL004B1"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 1449-Z02 (431232613)"],"award-info":[{"award-number":["SFB 1449-Z02 (431232613)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination elexacaftor\/tezacaftor\/ivacaftor (ELX\/TEZ\/IVA) was shown to improve clinical outcomes and sweat chloride concentration in patients with cystic fibrosis (CF) and one or two F508del alleles. However, the effect of ELX\/TEZ\/IVA on CFTR function in the airways and intestine has not been studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the effect of ELX\/TEZ\/IVA on CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles aged 12 years and older.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective, observational, multicenter study assessed clinical outcomes including FEV1% predicted and body mass index and the CFTR biomarkers sweat chloride concentration, nasal potential difference, and intestinal current measurement before and 8\u201316 weeks after initiation of ELX\/TEZ\/IVA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 107 patients with CF including 55 patients with one F508del and a minimal function mutation and 52 F508del homozygous patients were enrolled in this study. In patients with one F508del allele, nasal potential difference and intestinal current measurement showed that ELX\/TEZ\/IVA improved CFTR function in nasal epithelia to a level of 46.5% (interquartile range [IQR], 27.5\u201372.4; P\u2009&amp;lt;\u20090.001) and in intestinal epithelia to 41.8% of normal (IQR, 25.1\u201357.6; P\u2009&amp;lt;\u20090.001). In F508del homozygous patients, ELX\/TEZ\/IVA exceeded improvement of CFTR function observed with TEZ\/IVA and increased CFTR-mediated Cl\u2212 secretion to a level of 47.4% of normal (IQR, 19.3\u201369.2; P\u2009&amp;lt;\u20090.001) in nasal and 45.9% (IQR, 19.7\u201366.6; P\u2009&amp;lt;\u20090.001) in intestinal epithelia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment with ELX\/TEZ\/IVA results in effective improvement of CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT04732910).<\/jats:p>\n                  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