Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma

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.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.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.Smokers are particularly vulnerable to suffer from chronic obstructive pulmonary disease (COPD) and several co-morbidities [1,2]. The risk of COPD increases with age and smoking history [3-5], but very little is known about the cumulative effects of ageing and long-term smoking on human lungs.Several markers of oxidant burden and inflammation are elevated in smokers who have not developed obstruction/COPD [6-10]. However, these markers are not specific for smoking or COPD [10]. The epithelial lining fluid and mucins provide the first line of defense in the lung [11-14]. KL-6 is high-molecular-weight mucus glycoprotein also classified as a human MUC1 mucin [15-17]. Purified KL-6 can be detected by a