Year-end Sale % OFF 
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence.
Highlights
Chronic obstructive pulmonary disease (COPD) is an umbrella diagnosis that is characterised by airflow obstruction and permanent reduction of the forced expiratory volume [1]
Subjects and study design The Karolinska COSMIC cohort is a three-group cross-sectional study designed for investigating molecular sex differences in early-stage COPD, including 40 never-smokers (“healthy”), 40 smokers with normal lung function (“smokers”) and 38 individuals with COPD (Global Initiative for Chronic Obstructive Lung Disease stage I–II/A–B; forced expiratory volume in 1 s (FEV1) 51–97%; FEV1/forced vital capacity (FVC)
A total of 1153 putative metabolites were extracted from the nontargeted metabolomics raw data, of which 959 passed quality control
Summary
Chronic obstructive pulmonary disease (COPD) is an umbrella diagnosis that is characterised by airflow obstruction and permanent reduction of the forced expiratory volume [1]. The early diagnosis of COPD is challenging due to disease heterogeneity and lack of predictive molecular markers. The diagnosis is based solely on spirometry, while lung function, symptoms and exacerbation history are used for disease staging. Decline in lung function over time is accepted as a reliable index of disease progression; the mechanisms underlying different COPD subphenotypes and their relationship with prognosis are still unclear [3]. Evidence of sex differences, with higher mortality in females even after correction for smoking has emerged [4]. Smoking results in greater impairment in lung function in females, especially post-menopause [5, 6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
