TY - JOUR T1 - Lumacaftor/ivacaftor changes the lung microbiome and metabolome in cystic fibrosis patients JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00731-2020 SP - 00731-2020 AU - Anne H. Neerincx AU - Katrine Whiteson AU - Joann L. Phan AU - Paul Brinkman AU - Mahmoud I. Abdel-Aziz AU - Els J.M. Weersink AU - Josje Altenburg AU - Christof J. Majoor AU - Anke H. Maitland-van der Zee AU - Lieuwe D.J. Bos A2 - , , Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2020/11/06/23120541.00731-2020.abstract N2 - Rationale Targeted cystic fibrosis (CF) therapy with lumacaftor/ivacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes in the microbiome that is adapted to CF lungs may occur.Objectives To investigate the effects of lumacaftor/ivacaftor on respiratory microbial composition and microbial metabolic activity by repeatedly sampling the lower respiratory tract.Methods This was a single-center longitudinal observational cohort study in adult CF 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 a breath sample were collected before and every 3 months after starting therapy, up to 1 year.Results Twenty patients were included in this study. Amplicon 16S RNA and metagenomics sequencing revealed that Pseudomonas aeruginosa was most abundant in sputum and seemed to decrease after 6 months of treatment, although this did not reach statistical significance after correction for multiple testing. Two types of untargeted metabolomics analyses in sputum showed a change in metabolic composition between 3 and 9 months that almost returned to baseline levels after 12 months of treatment. The volatile metabolic composition of breath was significantly different after 3 months and remained different from baseline until 12 months follow up.Conclusions After starting CF transmembrane conductance regulator (CFTR) modulating treatment in CF patients with a homozygous Phe508del mutation, a temporary and moderate change in lung microbiome is observed, which is mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Neerincx has nothing to disclose.Conflict of interest: Dr. Whiteson has nothing to disclose.Conflict of interest: Dr. Phan has nothing to disclose.Conflict of interest: Dr. Brinkman has nothing to disclose.Conflict of interest: Dr. Abdel-Aziz reports a grant from Egyptian Government PhD Scholarship, outside the submitted work;.Conflict of interest: Dr. Weersink has nothing to disclose.Conflict of interest: Dr. Altenburg has nothing to disclose.Conflict of interest: Dr. Majoor has nothing to disclose.Conflict of interest: A.H. Maitland-van der Zee reports an Innovation Grant from Vertex outside the submitted work.Conflict of interest: Dr. Bos has nothing to disclose. ER -