title: Association of COPD exacerbation frequency with gene expression of pattern recognition receptors in inflammatory cells in induced sputum.
abstract: BACKGROUND
  Bacteria and viruses are major causes of chronic obstructive pulmonary disease (COPD) exacerbations. Molecular components of these pathogens are recognized by pattern-recognition receptors (PRRs) expressed by various cells in the airway, which leads to initiation of inflammatory processes. Expression levels of PRRs in airway inflammatory cells are expected to affect susceptibility to COPD exacerbation.
  
  
  OBJECTIVE
  This prospective observational study was conducted to detect any association between exacerbation and PRR expression.
  
  
  METHODS
  Thirty-one male COPD patients were recruited. At baseline, clinical history, lung function measurements, peripheral blood samples and induced sputum were obtained. Using sputum samples, we performed gene expression analysis of TLR2, TLR3, TLR4, NOD1, NOD2, RIG-I and MDA-5 by quantitative reverse transcription-polymerase chain reaction in addition to quantitative bacterial culture. COPD exacerbations were assessed based on Anthonisen's criteria using symptom diaries for the following 1-year period.
  
  
  RESULTS
  During 1-year follow-up period, 13 patients experienced at least one exacerbation, but 18 patients did not. Those with exacerbations tended to be more severe COPD and showed larger neutrophil fraction in their induced sputum. Among PRRs, only TLR3 gene expression was increased in COPD patients with exacerbation compared with those without exacerbations. Multivariate logistic regression analysis including neutrophil fraction and TLR3 gene expression as predictor variables demonstrated that only an increase of neutrophil fraction, but not TLR3 gene expression, was a significant predictor for COPD exacerbation.
  
  
  CONCLUSIONS
  TLR3 expression in inflammatory cells might affect the susceptibility to COPD exacerbation.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kinose
authors.affiliation: Health Administration Center and Division of Respiratory Medicine, Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Marumo
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kiyokawa
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Hirai
authors.affiliation: Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chin
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Muro
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000368:Aged; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013183:Sputum / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism
chemical_list: D051192:Receptors, Pattern Recognition; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3
keywords: COPD; TLR3; exacerbation; induced sputum; innate immune system