title: Lung microbiome dynamics in COPD exacerbations.
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.
authors.affiliation: Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA These authors contributed equally.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK These authors contributed equally.
authors.forename: Mona
authors.initials: M
authors.lastname: Bafadhel
authors.affiliation: 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.
authors.forename: Koirobi
authors.initials: K
authors.lastname: Haldar
authors.affiliation: Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Spivak
authors.affiliation: Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mayhew
authors.affiliation: Respiratory Therapy Area Unit, GSK R&D, King of Prussia, PA, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Miller
authors.affiliation: Respiratory Therapy Area Unit, GSK R&D, King of Prussia, PA, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Mohammadali Yavari
authors.initials: MY
authors.lastname: Ramsheh
authors.affiliation: Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barer
authors.affiliation: 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.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.affiliation: Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA Both authors contributed equally.
authors.forename: James R
authors.initials: JR
authors.lastname: Brown
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008137:Longitudinal Studies; D008168:Lung / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D010641:Phenotype; D025341:Principal Component Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000382:microbiology*; D011786:Quality Control; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013183:Sputum / Q000382:microbiology
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; C508606:CXCL8 protein, human; D018925:Chemokines; D016209:Interleukin-8; D012336:RNA, Ribosomal, 16S