{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T07:19:06Z","timestamp":1788679146018,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Elexacaftor\/tezacaftor\/ivacaftor (ETI) is a breakthrough therapy for cystic fibrosis (CF). We aimed to assess ETI's real\u2010world impact on peripheral airway disease assessed as ventilation distribution inhomogeneity using nitrogen multiple breath washout (N\n                      <jats:sub>2<\/jats:sub>\n                      MBW) in children aged 6\u201317 years. Additionally, we compared the two outcomes, lung clearance index (LCI), and ventilation distribution efficiency (VDE), as VDE is considered to adjust for a theoretical overestimation of lung disease when using LCI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This nationwide study included data from N\n                      <jats:sub>2<\/jats:sub>\n                      MBW performed during routine clinical care. Linear mixed effect regression was used to assess changes in LCI and VDE after 12 months of ETI treatment. Subgroup analyses included baseline age (6\u201311 vs. 12\u20131 years) and disease severity (normal\u2010moderate vs. severe\u2010very severe).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 131 children (78% homozygous for F508del mutation, mean [SD] age 11.5 [3.4]), and 339 N\n                      <jats:sub>2<\/jats:sub>\n                      MBW tests. The median (range) number of tests per child was 3 (1\u201010). The estimated mean (95% CI) 12\u2010months post\u2010ETI improvement in LCI and VDE were 1.7 units (\u22122.1; \u22121.2,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and 2.1%\u2010point (1.6; 2.6,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), respectively. Similar LCI and VDE improvements were observed across age groups. Using VDE, fewer children were categorized with very severe lung disease, and the ETI\u2010effect did not differ between the severity groups, unlike LCI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our research demonstrates that ETI treatment significantly improves lung function, as measured by N\n                      <jats:sub>2<\/jats:sub>\n                      MBW, in Danish children and adolescents with CF. VDE improvements were consistent across age and disease severity groups. In contrast, LCI revealed larger effect estimates for those with severe to very\u2010severe lung impairment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71166","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:15:13Z","timestamp":1750407313000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Real\u2010World Improvements of Lung Clearance Index and Ventilation Distribution Efficiency in Children With Cystic Fibrosis After Elexacaftor\/Tezacaftor\/Ivacaftor Initiation"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1247-8779","authenticated-orcid":false,"given":"Esben Herborg","family":"Henriksen","sequence":"first","affiliation":[{"name":"The Danish Cystic Fibrosis Cohort Copenhagen Denmark"},{"name":"Department of Infectious Diseases Rigshospitalet Copenhagen Denmark"},{"name":"Department of Pediatrics and Adolescent Medicine Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0374-7279","authenticated-orcid":false,"given":"Rikke Mulvad","family":"Sandvik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette Frahm","family":"Olsen","sequence":"additional","affiliation":[{"name":"The Danish Cystic Fibrosis Cohort Copenhagen Denmark"},{"name":"Department of Infectious Diseases Rigshospitalet Copenhagen Denmark"},{"name":"Department of Nutrition, Exercise and Sports, Faculty of Science University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tacjana","family":"Pressler","sequence":"additional","affiliation":[{"name":"The Danish Cystic Fibrosis Cohort Copenhagen Denmark"},{"name":"Department of Infectious Diseases Rigshospitalet Copenhagen Denmark"},{"name":"Department of Pediatrics and Adolescent Medicine Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8533-6766","authenticated-orcid":false,"given":"Thomas","family":"Bryrup","sequence":"additional","affiliation":[{"name":"The Danish Cystic Fibrosis Cohort Copenhagen Denmark"},{"name":"Department of Infectious Diseases Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Leo\u2010Hansen","sequence":"additional","affiliation":[{"name":"The Danish Cystic Fibrosis Cohort Copenhagen Denmark"},{"name":"Department of Infectious Diseases Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibi Uhre","family":"Nielsen","sequence":"additional","affiliation":[{"name":"The Danish Cystic Fibrosis Cohort Copenhagen Denmark"},{"name":"Department 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