title: Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma.
abstract: BACKGROUND
  KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history.
  
  
  METHODS
  The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201). The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28), were analyzed by immunohistochemistry and digital image analysis.
  
  
  RESULTS
  The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6.
  
  
  CONCLUSIONS
  KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.
authors.affiliation: Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Witold
authors.initials: W
authors.lastname: Mazur
authors.forename: Tuula
authors.initials: T
authors.lastname: Toljamo
authors.forename: Katri
authors.initials: K
authors.lastname: Vuopala
authors.forename: Mikko
authors.initials: M
authors.lastname: Rönty
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Horimasu
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Vuokko L
authors.initials: VL
authors.lastname: Kinnula
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005387:Finland; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism*
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1