CFTR modulator therapy with lumacaftor/ivacaftor alters plasma concentrations of lipid-soluble vitamins A and E in patients with cystic fibrosis

• Verfasst von: Sommerburg, Olaf [VerfasserIn]
• Verfasst von: Hämmerling, Susanne Hedwig [VerfasserIn]
• Verfasst von: Schneider, Philipp [VerfasserIn]
• Verfasst von: Okun, Jürgen G. [VerfasserIn]
• Verfasst von: Langhans, Claus-Dieter [VerfasserIn]
• Verfasst von: Leutz-Schmidt, Patricia [VerfasserIn]
• Verfasst von: Wielpütz, Mark Oliver [VerfasserIn]
• Verfasst von: Siems, Werner [VerfasserIn]
• Verfasst von: Gräber, Simon Y. [VerfasserIn]
• Verfasst von: Mall, Marcus A. [VerfasserIn]
• Verfasst von: Stahl, Mirjam [VerfasserIn]
• Titel: CFTR modulator therapy with lumacaftor/ivacaftor alters plasma concentrations of lipid-soluble vitamins A and E in patients with cystic fibrosis
• Verf.angabe: Olaf Sommerburg, Susanne Hämmerling, S. Philipp Schneider, Jürgen Okun, Claus-Dieter Langhans, Patricia Leutz-Schmidt, Mark O. Wielpütz, Werner Siems, Simon Y. Gräber, Marcus A. Mall and Mirjam Stahl
• E-Jahr: 2021
• Jahr: 19 March 2021
• Umfang: 15 S.
• Teil: volume:10
• Teil: year:2021
• Teil: number:3
• Teil: elocationid:483
• Teil: pages:1-15
• Teil: extent:15
• Fussnoten: Der Artikel erschien im Special Issue "Commemorative issue of antioxidants dedicated to Peter Eckl" ; Gesehen am 07.05.2021
• Titel Quelle: Enthalten in: Antioxidants
• Ort Quelle: Basel : MDPI, 2013
• Jahr Quelle: 2021
• Band/Heft Quelle: 10(2021), 3, Artikel-ID 483, Seite 1-15
• ISSN Quelle: 2076-3921
• DOI: doi:10.3390/antiox10030483
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CFTR modulators
• Sach-SW: cystic fibrosis
• Sach-SW: hypervitaminosis A
• Sach-SW: retinol
• Sach-SW: therapy
• Sach-SW: vitamin E
• K10plus-PPN: 1757486623

Abstract

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 < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 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 µmol/L (p < 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.