TY - JOUR T1 - Profiling of airway epithelial proteome reveals sex differences in early stage COPD linked to xenobiotic metabolism and ER stress JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.3829 VL - 56 IS - suppl 64 SP - 3829 AU - Tina Heyder AU - Mingxing Yang AU - Maxie Kohler AU - Heta Merikallio AU - Helena Forsslund AU - Chuan-Xing Li AU - Reza Karimi AU - Johan Grunewald AU - Riitta Kaarteenaho AU - Carina Sihlbom AU - C. Magnus Skold AU - Åsa Wheelock Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/3829.abstract N2 - COPD is a heterogeneous disease with suggested impact of sex on disease onset and course, as well as on clinical and molecular phenotype.The aim of this study was to investigate alterations in the airway epithelial proteome in smoking-induced COPD, with emphasis on sex-differences.The airway epithelial proteome from age- and sex-matched smoking COPD patients (GOLD I-II/A-B), smokers with normal lung function (Smokers), and never-smoker healthy controls (Healthy) from the Karolinska COSMIC cohort (n=90) was analysed by multiplexed shotgun- and gel-based proteomics. Data analysis was performed by multivariate statistical modelling and pathway enrichment analyses.Significant sex-differences between COPD and Smoker groups was evident by both platforms, with distinct protein subsets providing significant classification in females and males (Figure 1A-B). Alterations were linked to dysregulation in protein folding in the ER, xenobiotic metabolism and oxidative phosphorylation. In female COPD patients, oxidative phosphorylation and protein processing in the ER correlated with airway wall thickness as measure by CT, while Protein folding in the ER correlated with goblet cell density (Figure 1C-E).This study demonstrates significant sex differences in the airway epithelial proteome in smoking-induced COPD, indicating divergent molecular COPD sub-phenotypes between the sexes. Figure 1FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3829.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). ER -