期刊
ERJ OPEN RESEARCH
卷 7, 期 2, 页码 -出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/23120541.00731-2020
关键词
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资金
- Dutch Lung Foundation (Longfonds) Young Investigator Award
This study investigated the effects of lumacaftor/ivacaftor on the respiratory microbial composition and microbial metabolic activity in CF patients. Results showed a temporary change in lung microbiome characterized by a reduction in the relative abundance of Pseudomonas aeruginosa after CFTR modulating treatment, which eventually returned to baseline levels. The volatile metabolic composition in breath also exhibited significant differences from baseline, indicating potential ongoing changes in microbial activity even after 12 months of treatment.
Rationale: Targeted cystic fibrosis (CF) therapy with lumacaftor/ivacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes may occur in the microbiome, which is adapted to CF lungs. 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-centre 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, for up to 12 months. 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 the lung microbiome is observed, which is mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa.
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