Late Breaking Abstract - Increased serum levels of YKL-40 in male smoking chronic obstructive pulmonary disease patients associated with altered miRNA levels in alveolar macrophages

Abstract

Background: The protein YKL-40 (CHI3L1) is associated with smoking and chronic obstructive pulmonary disease (COPD). Smoking is a major risk factor for COPD, and the importance of gender on molecular COPD sub-phenotypes is emerging.

Aims and Objectives: To investigate the influence of gender and smoking on YKL-40 levels, and putative regulatory mechanisms of YKL-40 expression in the lung.

Methods: YKL-40 was quantified by ELISA in serum and bronchoalveolar lavage (BAL) fluid in never-smokers (n=40), smokers with normal lung function (n=40), as well as smokers (n=27) and ex-smokers (n=11) with mild to moderate COPD. CHI3L1 mRNA and associated miRNA were quantified in BAL cells and bronchial epithelial cells (BEC) using microarray.

Results: Serum YKL-40 was significantly elevated in the male smoking COPD patients compared to male smokers without COPD (p<0.05) and male healthy never-smokers (p<0.01). Furthermore, serum YKL-40 levels correlated with goblet cell abundance (r=0.71) and mean corpuscular hemoglobin (r=0.75) in male smoking COPD patients. In BAL fluid, no significant differences in YKL-40 levels were observed. CHI3L1 mRNA levels in BAL cells were altered in a similar fashion to serum YKL-40 levels, with no alterations observed in BEC. A subset of 10 miRNA known to target CHI3L1 were decreased in BAL cells of male COPD-smokers versus male smokers.

Conclusions: Alveolar macrophages, which make up >85% of BAL cells, could account for the higher YKL-40 serum levels observed in smoking men with COPD, possibly via specific miRNA. This could point towards a male-dominated COPD sub-phenotype associated with chitinase alterations.