Open Access Research article

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

Nobuhisa Ishikawa12, Witold Mazur1, Tuula Toljamo3, Katri Vuopala4, Mikko Rönty5, Yasushi Horimasu2, Nobuoki Kohno2 and Vuokko L Kinnula1*

Author Affiliations

1 Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

2 Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

3 Department of Medicine, Pulmonary Division, Lapland Central Hospital, Rovaniemi, Finland

4 Department of Pathology, Lapland Central Hospital, Rovaniemi, Finland

5 Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

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BMC Pulmonary Medicine 2011, 11:22  doi:10.1186/1471-2466-11-22

Published: 11 May 2011



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.


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.