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


Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
01 2021
Historique:
received: 26 10 2019
revised: 17 02 2020
accepted: 18 02 2020
pubmed: 1 5 2020
medline: 27 7 2021
entrez: 1 5 2020
Statut: ppublish

Résumé

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. Our aim was to investigate the COPD sputum microbiome and its association with inflammatory phenotypes and mortality. 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. 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 FEV 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.

Sections du résumé

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 FEV
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.

Identifiants

pubmed: 32353489
pii: S0091-6749(20)30566-2
doi: 10.1016/j.jaci.2020.02.040
pii:
doi:

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

158-167

Informations de copyright

Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Auteurs

Alison J Dicker (AJ)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Jeffrey T J Huang (JTJ)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Mike Lonergan (M)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Holly R Keir (HR)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Christopher J Fong (CJ)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Brandon Tan (B)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Andrew J Cassidy (AJ)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Simon Finch (S)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom.

Hana Mullerova (H)

Medical Innovation, GSK R&D, Collegeville, Pa.

Bruce E Miller (BE)

Medical Innovation, GSK R&D, Collegeville, Pa.

Ruth Tal-Singer (R)

Medical Innovation, GSK R&D, Collegeville, Pa.

James D Chalmers (JD)

the Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom. Electronic address: jchalmers@dundee.ac.uk.

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