Metabolomic responses to lumacaftor/ivacaftor in cystic fibrosis.

摘要: BACKGROUND Cystic fibrosis (CF) is a life-limiting disease caused by defect in the cystic transmembrane conductance regulator (CFTR) gene. Lumacaftor/Ivacaftor novel CFTR modulator approved for patients that are homozygous Phe508del CFTR, but its clinical effectiveness varies amongst patients, making it difficult to determine responders. Therefore, identifying biochemical biomarkers associated with drug response clinically important follow-up studies. METHODS Serum metabolomics was performed on twenty CF pre- and 6-month post-Lumacaftor/Ivacaftor via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Correlation variables performed. RESULTS Metabolomics analysis demonstrated 188 differentially regulated metabolites between initiation, predominance of lipid amino acid alterations. The top 30 were able differentiate status greater than 90% random-forest confusion matrix. Alterations bile acids, phospholipids, bacteria-associated predominant changes response. Importantly, metabolic patterns CONCLUSIONS Selected key pathways significantly affected initiation similar Targeted may provide useful relevant responses.