title: The association of down-regulated toll-like receptor 4 expression with airflow limitation and emphysema in smokers.
abstract: BACKGROUND
  An association between innate immunity including Toll-like receptors (TLRs) and COPD is reported recently; TLR4 deficiency in lung can cause emphysema in animals, which is not evident in humans. We analyzed the association of TLR4 expression, airflow limitation and emphysema in smokers.
  
  
  METHODS
  We enrolled patients of ≥40years old with smoking histories of ≥10 pack-years and who had undergone lung resection. We measured TLR4 expression in lung lysates. The severity of emphysema was evaluated on computed tomography. TLR4 expression was also evaluated immunohistochemically.
  
  
  RESULTS
  In total, 53 patients were enrolled. Forced expiratory volume in one second per forced vital capacity (FEV1/FVC) increased (P=0.03) and emphysema score decreased (P=0.01) as TLR4 expression increased. These were still significant, in multiple regression analysis including sex, age, tuberculosis history, smoking history and inhaled corticosteroid (ICS) usage. We also classified patients as high, intermediate, and low expressers according to TLR4 expression. Although no differences in age, gender, tuberculosis, or smoking history were observed among the groups, emphysema severity increased significantly (P = 0.02) and FEV1/FVC decreased significantly (P = 0.006) in TLR4 low expresser. The difference in TLR4 expression based on immunohistochemistry was most prominent in bronchial and alveolar epithelial cells.
  
  
  CONCLUSIONS
  Down-regulated TLR4 expression in lung was associated with emphysema and airflow limitation in smokers.
authors.affiliation: Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Dal Rae
authors.initials: DR
authors.lastname: Kim
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Kim
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Paik
authors.forename: Jin-Haeng
authors.initials: JH
authors.lastname: Chung
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Jheon
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Huh
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D015536:Down-Regulation; D004646:Emphysema / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4