{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:29Z","timestamp":1787027549148,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["82DZL004A1"],"award-info":[{"award-number":["82DZL004A1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM\/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM\/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM\/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM\/IVA therapy. Results: Patients with CF receiving LUM\/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g\/L after two years (p &lt; 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 \u00b5mol\/L (p &lt; 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E\/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 \u00b5mol\/L (p &lt; 0.01). Conclusions: CFTR modulator therapy with LUM\/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.<\/jats:p>","DOI":"10.3390\/antiox10030483","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T11:18:38Z","timestamp":1616152718000},"page":"483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["CFTR Modulator Therapy with Lumacaftor\/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3941-8944","authenticated-orcid":false,"given":"Olaf","family":"Sommerburg","sequence":"first","affiliation":[{"name":"Division of Pediatric Pulmonology &amp; Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"},{"name":"Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"H\u00e4mmerling","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology &amp; Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany"},{"name":"Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Philipp","family":"Schneider","sequence":"additional","affiliation":[{"name":"Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Okun","sequence":"additional","affiliation":[{"name":"Center for Pediatric and Adolescent Medicine, Department of Paediatrics I, Division of Neuropediatrics and Metabolic Medicine and Newborn Screening Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus-Dieter","family":"Langhans","sequence":"additional","affiliation":[{"name":"Center for Pediatric and Adolescent Medicine, Department of Paediatrics I, Division of Neuropediatrics and Metabolic Medicine and Newborn Screening Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Leutz-Schmidt","sequence":"additional","affiliation":[{"name":"Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark O.","family":"Wielp\u00fctz","sequence":"additional","affiliation":[{"name":"Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"},{"name":"Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Siems","sequence":"additional","affiliation":[{"name":"Clinics for Prevention and Rehabilitation, 38667 Bad Harzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1666-8924","authenticated-orcid":false,"given":"Simon Y.","family":"Gr\u00e4ber","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charite -Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"},{"name":"German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2199","authenticated-orcid":false,"given":"Marcus A.","family":"Mall","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charite -Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"},{"name":"German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-8315","authenticated-orcid":false,"given":"Mirjam","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charite -Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"},{"name":"German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic Fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15010","DOI":"10.1038\/nrdp.2015.10","article-title":"Cystic Fibrosis","volume":"1","author":"Ratjen","year":"2015","journal-title":"Nat. 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