CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis

Antioxidants

Claus-Dieter Langhans¹  Jürgen Okun¹  Werner Siems²  Olaf Sommerburg³  Susanne Hämmerling³  Mirjam Stahl⁴  MarcusA. Mall⁴  SimonY. Gräber⁴  S.Philipp Schneider⁵  MarkO. Wielpütz⁵  Patricia Leutz-Schmidt⁵ 

[1] 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;Clinics for Prevention and Rehabilitation, 38667 Bad Harzburg, Germany;Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany;Immunology and Critical Care Medicine and Cystic Fibrosis Center, Department of Pediatric Pulmonology, Charite-Universitätsmedizin Berlin, 13353 Berlin, Germany;Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany;

关键词: cystic fibrosis;    CFTR modulators;    therapy;    retinol;    vitamin E;    hypervitaminosis A;   

DOI  :  10.3390/antiox10030483

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown