RT Journal Article
SR Electronic
T1 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
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 4714
DO 10.1183/13993003.congress-2020.4714
VO 56
IS suppl 64
A1 Benedikt Zöhrer
A1 Anna James
A1 Nabil Souihi
A1 Bettina Brundin
A1 Reza Karimi
A1 David J. Erle
A1 Sven-Eric Dahlén
A1 C. Magnus Sköld
A1 Åsa M. Wheelock
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/4714.abstract
AB 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.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4714.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).