Abstract
<jats:p>Background Chronic obstructive pulmonary disease, primarily caused by exposure to cigarette smoke, is a heterogeneous lung condition characterized by complex metabolic alterations. The metabolic changes associated with smoking status have not been thoroughly investigated. Our study aims to explore the metabolite profile of COPD patients categorised by their smoking habits, including smokers, ex-smokers, and non-smokers. Methods In this study, the plasma metabolome of smoking stratified COPD patients were assessed using gas chromatography coupled to mass spectrometry. We applied multivariate and univariate statistical analysis to identify the differentially abundant metabolites. Results We identified 23 altered metabolites in the smokers and 36 in the ex-smokers COPD subgroups. Interestingly, in comparison to the control group, no significant alteration was observed in the plasma of non-smoker COPD patients. Additionally, pathway enrichment analysis revealed top dysregulated metabolic pathways, including biosynthesis of unsaturated fatty acids, galactose metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The receiver operating characteristic curve screened five metabolites, such as tetradecanoic acid, 2,4-di-tert-butylphenol, chloroxylenol, tetradecanal, and 1-dodecene, with the highest diagnostic performance (AUC > 0.8). Conclusion This study reveals distinct plasma metabolic signatures across COPD subgroups categorized by cigarette smoking history.</jats:p>