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      Lung microbiome dynamics in COPD exacerbations.

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          Abstract

          Increasing evidence suggests that the lung microbiome plays an important role in chronic obstructive pulmonary disease (COPD) severity. However, the dynamics of the lung microbiome during COPD exacerbations and its potential role in disease aetiology remain poorly understood.We completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on 476 sputum samples collected from 87 subjects with COPD at four visits defined as stable state, exacerbation, 2 weeks post-therapy and 6 weeks recovery.Our analysis revealed a dynamic lung microbiota where changes appeared to be associated with exacerbation events and indicative of specific exacerbation phenotypes. Antibiotic and steroid treatments appear to have differential effects on the lung microbiome. We depict a microbial interaction network for the lung microbiome and suggest that perturbation of a few bacterial operational taxonomic units, in particular Haemophilus spp., could greatly impact the overall microbial community structure. Furthermore, several serum and sputum biomarkers, in particular sputum interleukin-8, appear to be highly correlated with the structure and diversity of the microbiome.Our study furthers the understanding of lung microbiome dynamics in COPD patients and highlights its potential as a biomarker, and possibly a target, for future respiratory therapeutics.

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          Author and article information

          Journal
          Eur. Respir. J.
          The European respiratory journal
          European Respiratory Society (ERS)
          1399-3003
          0903-1936
          Apr 2016
          : 47
          : 4
          Affiliations
          [1 ] Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA These authors contributed equally.
          [2 ] Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK These authors contributed equally.
          [3 ] Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK Dept of Health Sciences, University of Leicester, Leicester, UK.
          [4 ] Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA.
          [5 ] Respiratory Therapy Area Unit, GSK R&D, King of Prussia, PA, USA.
          [6 ] Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
          [7 ] Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
          [8 ] Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK Dept of Health Sciences, University of Leicester, Leicester, UK Both authors contributed equally ceb17@leicester.ac.uk.
          [9 ] Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA Both authors contributed equally.
          Article
          13993003.01406-2015
          10.1183/13993003.01406-2015
          26917613

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