title: Association between pathogens detected using quantitative polymerase chain reaction with airway inflammation in COPD at stable state and exacerbations.
abstract: BACKGROUND
  Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear. Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.
  
  
  METHODS
  Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform. Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR. Symptoms were quantified using the visual analog scale.
  
  
  RESULTS
  At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae. Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis. Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α. H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β. In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.
  
  
  CONCLUSIONS
  At stable state, H influenzae is associated with increased airway inflammation in COPD. The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation.
authors.affiliation: Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, and the Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester.
authors.forename: Bethan L
authors.initials: BL
authors.lastname: Barker
authors.affiliation: Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, and the Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester.
authors.forename: Koirobi
authors.initials: K
authors.lastname: Haldar
authors.affiliation: Department of Clinical Microbiology, University Hospitals of Leicester National Health Service Trust, Leicester.
authors.forename: Hemu
authors.initials: H
authors.lastname: Patel
authors.affiliation: Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Oxford, England.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Pavord
authors.affiliation: Institute for Lung Health, National Institute for Health Research Respiratory Biomedical Research Unit, and the Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester; Department of Clinical Microbiology, University Hospitals of Leicester National Health Service Trust, Leicester.
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, and the Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.affiliation: Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Oxford, England. Electronic address: mona.bafadhel@ndm.ox.ac.uk.
authors.forename: Mona
authors.initials: M
authors.lastname: Bafadhel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001419:Bacteria / Q000235:genetics* / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000032:analysis*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology*; D013183:Sputum / Q000382:microbiology*
chemical_list: D004269:DNA, Bacterial
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