The sputum microbiome has a potential role in disease phenotyping and risk stratification in chronic obstructive pulmonary disease but few large longitudinal cohort studies exist.
To investigate the COPD sputum microbiome and its association with inflammatory phenotypes and mortality.
16S rRNA gene sequencing was performed on sputum from 253 clinically stable COPD patients (4-years median follow-up). Samples were classified as Proteobacteria or Firmicutes (phylum level) and Haemophilus or Streptococcus (genera level) dominant. Alpha diversity was measured using Shannon-Wiener Diversity and Berger-Parker Dominance Indices. Survival was modelled using Cox proportional hazards regression. A subset of 78 patients had label-free liquid chromatography/mass spectrometry performed, with partial least square discriminant analysis integrating clinical, microbiome and proteomics data.
Proteobacteria dominance and lower diversity was associated with more severe COPD using the GOLD classification system (p=0·0015), more frequent exacerbations (p=0·0042), blood eosinophils ≤100cells/μL (p<0·0001) and lower FEV (p=0·026). Blood eosinophil counts showed a positive relationship with %Firmicutes and Streptococcus, and a negative association with %Proteobacteria and Haemophilus. Proteobacteria dominance was associated with increased mortality compared to Firmicutes dominated or balanced microbiome profiles (HR 2·58 95%CI 1·43-4·66, p=0·0017 and HR 7·47 95%CI 1·02-54·86, p=0·048 respectively). Integrated omics analysis showed significant associations between Proteobacteria dominance and the neutrophil activation pathway in sputum.
The sputum microbiome is associated with clinical and inflammatory phenotypes in COPD. Reduced microbiome diversity, associated with Proteobacteria (predominantly Haemophilus) dominance, is associated with neutrophil associated protein profiles and an increased risk of mortality.

Copyright © 2020. Published by Elsevier Inc.