Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study
Zhang Wang, Richa Singh, Bruce E Miller, Ruth Tal-Singer, Stephanie Van Horn, Lynn Tomsho, Alexander Mackay, James P Allinson, Adam J Webb, Anthony J Brookes, Leena M George, Bethan Barker, Umme Kolsum, Louise E Donnelly, Kylie Belchamber, Peter J Barnes, Dave Singh, Christopher E Brightling, Gavin C Donaldson, Jadwiga A Wedzicha, James R Brown, COPDMAP, Zhang Wang, Richa Singh, Bruce E Miller, Ruth Tal-Singer, Stephanie Van Horn, Lynn Tomsho, Alexander Mackay, James P Allinson, Adam J Webb, Anthony J Brookes, Leena M George, Bethan Barker, Umme Kolsum, Louise E Donnelly, Kylie Belchamber, Peter J Barnes, Dave Singh, Christopher E Brightling, Gavin C Donaldson, Jadwiga A Wedzicha, James R Brown, COPDMAP
Abstract
Background: Recent studies suggest that lung microbiome dysbiosis, the disease associated disruption of the lung microbial community, might play a key role in chronic obstructive pulmonary disease (COPD) exacerbations. However, characterising temporal variability of the microbiome from large longitudinal COPD cohorts is needed to better understand this phenomenon.
Methods: We performed a 16S ribosomal RNA survey of microbiome on 716 sputum samples collected longitudinally at baseline and exacerbations from 281 subjects with COPD at three UK clinical centres as part of the COPDMAP consortium.
Results: The microbiome composition was similar among centres and between stable and exacerbations except for a small significant decrease of Veillonella at exacerbations. The abundance of Moraxella was negatively associated with bacterial alpha diversity. Microbiomes were distinct between exacerbations associated with bacteria versus eosinophilic airway inflammation. Dysbiosis at exacerbations, measured as significant within subject deviation of microbial composition relative to baseline, was present in 41% of exacerbations. Dysbiosis was associated with increased exacerbation severity indicated by a greater fall in forced expiratory volume in one second, forced vital capacity and a greater increase in CAT score, particularly in exacerbations with concurrent eosinophilic inflammation. There was a significant difference of temporal variability of microbial alpha and beta diversity among centres. The variation of beta diversity significantly decreased in those subjects with frequent historical exacerbations.
Conclusions: Microbial dysbiosis is a feature of some exacerbations and its presence, especially in concert with eosinophilic inflammation, is associated with more severe exacerbations indicated by a greater fall in lung function.
Trial registration number: Results, NCT01620645.
Keywords: bacterial infection; copd exacerbations; copd pathology.
Conflict of interest statement
Competing interests: ZW, BEM, RT-S, SVH, LT and JRB were employees and shareholders in GlaxoSmithKline PLC at the time of this study. Other authors have no competing interest to declare.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Source: PubMed