Changes in Airway Microbiome and Inflammation with Ivacaftor Treatment in Patients with Cystic Fibrosis and the G551D Mutation

作者：Jonathan Kirk Harris, Brandie D. Wagner, Edith T. Zemanick, Charles E. Robertson, Mark J. Stevens, Sonya L. Heltshe, Steven Mark Rowe, Scott D. Sagel · 发表于：Annals of the American Thoracic Society · 年份：2019 · DOI：10.1513/annalsats.201907-493oc · 被引用次数：155 · 研究领域：Cystic Fibrosis Research Advances、Pediatric health and respiratory diseases、Breastfeeding Practices and Influences

Abstract Rationale Modulation of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein improves clinical outcomes in patients with CF and specific CFTR genetic mutations. It remains unclear how improving CFTR function modifies existing airway infection and inflammation. Objectives To compare sputum microbiome and markers of inflammation before and after 6 months of ivacaftor treatment. Methods The study included 31 people with CF, ages 10 years and older, with at least one G551D CFTR allele and an forced expiratory volume in 1 second (FEV1) of 40% predicted or greater who were enrolled in the GOAL (G551D Observational) study. Sputum samples were collected either by induction (n = 14) or by spontaneous expectoration (n = 17) before and 6 months after initiation of ivacaftor. Changes in bacterial community indices by sequencing of 16S rRNA amplicons, total and specific bacterial load, and a panel of proteases, antiproteases, and inflammatory cytokines were determined. Results The cohort that spontaneously expectorated sputum had a lower FEV1, a higher proportion with Pseudomonas aeruginosa infection, and higher concentrations of sputum inflammatory markers compared with the cohort that provided sputum by induction. Although the overall cohort experienced significant improvements in FEV1 and reductions in sweat chloride, no significant changes in bacterial diversity, specific bacterial pathogens, or markers of inflammation were observed in these subjects. N...