CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis
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,
Mirjam Stahl
Affiliations
Olaf Sommerburg
Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
Susanne Hämmerling
Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
S. Philipp Schneider
Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany
Jürgen Okun
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
Claus-Dieter Langhans
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
Patricia Leutz-Schmidt
Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany
Mark O. Wielpütz
Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany
Werner Siems
Clinics for Prevention and Rehabilitation, 38667 Bad Harzburg, Germany
Simon Y. Gräber
Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charite -Universitätsmedizin Berlin, 13353 Berlin, Germany
Marcus A. Mall
Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charite -Universitätsmedizin Berlin, 13353 Berlin, Germany
Mirjam Stahl
Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charite -Universitätsmedizin Berlin, 13353 Berlin, Germany
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 p 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.
