Metabolomics Reveals Dysregulated Sphingolipid and Amino Acid Metabolism Associated with Chronic Obstructive Pulmonary Disease

Abstract

Purpose: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease presenting as multiple phenotypes, such as declining lung function, emphysema, or persistent airflow limitation caused by several risk factors, including cigarette smoking and air pollution. The inherent complexity of COPD phenotypes propounds difficulties for accurate diagnosis and prognosis. Although metabolomic profiles on COPD have been reported, the role of metabolism in COPD-related phenotypes is yet to be determined. In this study, we investigated the association between plasma sphingolipids and amino acids, and between COPD and COPD-related phenotypes in a Korean cohort. Patients and Methods: Blood samples were collected from 120 patients with COPD and 80 control participants who underwent spirometry and quantitative computed tomography. The plasma metabolic profiling was carried out using LC-MS/MS analysis. Results: Among the evaluated plasma sphingolipids, an increase in the metabolism of two specific sphingomyelins, SM (d18:1/24:0) and SM (d18:1/24:1) were significantly associated with COPD. There was no significant correlation between any of the SMs and the emphysema index, FVC and FEV 1 in the COPD cohort. Meanwhile, Cer (d18:1/18:0) and Cer (d18:1/24:1) were significantly associated with reduced FEV 1 . Furthermore, the levels of several amino acids were altered in the COPD group compared to that in the non-COPD group; glutamate and alpha AAA were substantial associated with emphysema in COPD. Kynurenine was the only amino acid significantly associated with reduced FEV 1 in COPD. In contrast, there was no correlation between FVC and the elevated metabolites. Conclusion: Our results provide dysregulated plasma metabolites impacting COPD phenotypes, although more studies are needed to explore the underlying mechanism related to COPD pathogenesis. Keywords: targeted sphingolipids, amino acids, sub-phenotypes, lung function