The sputum microbiome, airway inflammation, and mortality in chronic obstructive pulmonary disease - 09/01/21
Abstract |
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 < .0001), and lower FEV1 (P = .026). Blood eosinophil counts showed a positive relationship with percent of Firmicutes and Streptococcus and a negative association with percent Proteobacteria and Haemophilus. Proteobacteria dominance was associated with increased mortality compared with Firmicutes-dominated or balanced microbiome profiles (hazard ratio = 2.58; 95% CI = 1.43-4.66; P = .0017 and hazard ratio = 7.47; 95% CI = 1.02-54.86; P = .048, respectively). Integrated omics analysis showed significant associations between Proteobacteria dominance and the neutrophil activation pathway in sputum.
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.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key words : Microbiome, COPD, eosinophil, phenotype, Haemophilus
Abbreviations used : aHR, BPDI, COPD, FDR, FVC, GOLD, HR, ICS, OTU, SWDI
Mappa
| This study was funded by GlaxoSmithKline and by the British Lung Foundation through the GSK-BLF Chair of Respiratory Research to J.D.C. |
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| Disclosure of potential conflict of interest: J. D. Chalmers reports grants from GlaxoSmithKline for this research; in addition, he reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer Healthcare, Grifols, Napp, Aradigm Corporation, and Insmed outside the submitted work. H. Mullerova and R. Tal-Singer were employees of GlaxoSmithKline when this study was conducted. R. Tal-Singer is a shareholder of GlaxoSmithKline. B. E. Miller is an employee and shareholder of GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 1
P. 158-167 - Gennaio 2021 Ritorno al numero
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