The sputum microbiome, airway inflammation, and mortality in chronic obstructive pulmonary disease

Background The sputum microbiome has a potential role in disease phenotyping and risk stratification in chronic obstructive pulmonary disease (COPD), but few large longitudinal cohort studies exist. Objective Our aim was to investigate the COPD sputum microbiome and its association with inflammatory phenotypes and mortality. Methods 16S ribosomal RNA gene sequencing was performed on sputum from 253 clinically stable COPD patients (4-year median follow-up). Samples were classified as Proteobacteria or Firmicutes (phylum level) and Haemophilus or Streptococcus (genus level) dominant. Alpha diversity was measured by using Shannon-Wiener diversity and Berger-Parker dominance indices. Survival was modeled by using Cox proportional hazards regression. A subset of 78 patients had label-free liquid chromatography with tandem mass spectrometry performed, with partial least square discriminant analysis integrating clinical, microbiome, and proteomics data. Results Proteobacteria dominance and lower diversity was associated with more severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease classification system (P = .0015), more frequent exacerbations (P = .0042), blood eosinophil level less than or equal to 100 cells/μL (P  Conclusion 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.