Dysregulated serum glycerophospholipid and fatty acid metabolism in different disease stages of COPD

<bold>Background:</bold> Exploring the serum metabolic profile of COPD patients in different disease stages and its relationship with respiratory immunity will help advance our understanding of the pathogenesis and improve clinical management. <bold>Methods:</bold> A total of 107 longitudinal serum samples from 31 COPD patients and 20 serum samples from healthy controls were subjected to untargeted metabolic profiling, and the sputum supernatant was analyzed for 12 cytokines using a Luminex assay. <bold>Results:</bold> Serum glycerophospholipid metabolism and fatty acid metabolism were significantly dysregulated in COPD patients. Increased phosphatidylcholine (PC) and decreased lysophosphatidylcholine (LPC) were observed in both acute exacerbation (AE) and stable stage of COPD. We identified a number of differentially expressed metabolites unique to AE and stable stage (34 and 46 metabolites, respectively). Arachidonic acid metabolism was significantly unbalanced in AE, manifested as increased levels of metabolites in the cyclooxygenase (COX) pathway and decreased levels of metabolites in the lipoxygenase (LOX) and cytochrome P450 (CYP) pathways. Fatty acid metabolism was significantly altered in the stable stage, with decreased levels of various long-chain fatty acids and long-chain fatty acylcarnitines. Multiple associations were observed between serum metabolites and clinical parameters. Furthermore, correlation network analysis suggested that Th17 cytokines (IL-17A and IL-22) were closely related to PC (18:4/P-18:1) and phosphatidylserine (PS; 20:5/18:1). <bold>Conclusions:</bold> Serum glycerophospholipid metabolism and fatty acid metabolism may constitute potential targets for the management of COPD.