Start of ivacaftor/lumacaftor in adult cystic fibrosis patients with homozygous Phe508del results in temporal changes in lung microbiome and metabolome.

Rationale: Targeted cystic fibrosis therapy with ivacaftor/lumacaftor partly restores chloride channel function in the airways and increases of the epithelial fluid transport in the airways. Consequently, changes in the microbiome that is adapted to cystic fibrosis lungs can occur.Objectives: To investigate the effects of ivacaftor/lumacaftor on respiratory microbial composition and microbial metabolic activity in an observational cohort study, in which we repeatedly sampled the lower respiratory tract.Methods: This was a single-center longitudinal observational cohort study in adult cystic fibrosis patients with a homozygous Phe508del mutation. Lung function measurements and microbial cultures of sputum were performed as part of routine care. An oral and nasal wash, and an exhaled breath sample were collected before and every three months after starting therapy, up to one year.