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Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis.

ABSTRACT: RATIONALE:The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation. OBJECTIVES:To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF. METHODS:Infants with CF from U.S. and Australian centers were enrolled in a prospective, observational study examining the bacterial microbiota and inflammatory profiles of the respiratory tract. Bacterial diversity and density (load) were measured. Lavage samples were analyzed for inflammatory markers (interleukin 8, unbound neutrophil elastase, and absolute neutrophil count) in the epithelial lining fluid. RESULTS:Thirty-two infants (mean age, 4.7 months) underwent bronchoalveolar lavage and oropharyngeal sampling. Shannon diversity strongly correlated between upper and lower airway samples from a given subject, although community compositions differed. Microbial diversity was lower in younger subjects and in those receiving daily antistaphylococcal antibiotic prophylaxis. In lavage samples, reduced diversity correlated with lower interleukin 8 concentration and absolute neutrophil count. CONCLUSIONS:In infants with CF, reduced bacterial diversity in the upper and lower airways was strongly associated with the use of prophylactic antibiotics and younger age at the time of sampling; less diversity in the lower airway correlated with lower inflammation on bronchoalveolar lavage. Our findings suggest modification of the respiratory microbiome in infants with CF may influence airway inflammation.

SUBMITTER: Pittman JE

PROVIDER: S-EPMC5718571 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis.

Pittman Jessica E JE Wylie Kristine M KM Akers Kathryn K Storch Gregory A GA Hatch Joseph J Quante Jane J Frayman Katherine B KB Clarke Nadeene N Davis Miriam M Stick Stephen M SM Hall Graham L GL Montgomery Gregory G Ranganathan Sarath S Davis Stephanie D SD Ferkol Thomas W TW

Annals of the American Thoracic Society 20171001 10

<h4>Rationale</h4>The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation.<h4>Objectives</h4>To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions i ...[more]

PMID: 28708417

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Project description: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. Neither total bacterial load nor presence of Pseudomonas changed significantly between paired samples with ivacaftor treatment. Younger patients experienced more shifts in their microbial communities than older patients.Conclusions: In this multicenter cohort, 6 months of ivacaftor treatment were not associated with significant changes in airway microbial communities or measures of inflammation. These data suggest that concomitant antimicrobial and antiinflammatory treatments will still be needed to manage airway disease in patients with CF treated with highly effective CFTR modulator therapy, especially in older patients with more advanced disease.

Dataset Information

Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis.

Publications

Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis.

Similar Datasets

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