Characterizing COPD phenotypes with a targeted signaling lipids metabolomics approach

Abstract

Aims: This study aimed to elucidate clinically-relevant classifications of COPD using a targeted metabolomics approach focusing on signaling lipids.

Materials and methods: Using a targeted LC-MS/MS platform, 166 metabolites including free fatty acids, prostaglandins, isoprostanes, lysophospholipids, endocannabinoids, and bile acids were profiled in a cohort of 49 COPD patients. The study integrated metabolomic data with clinical parameters to identify key metabolites and related pathways for various COPD classification systems including Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading stages, Koninklijk Nederlands Genootschap voor Fysiotherapie (KNGF, Royal Dutch Society for Physiotherapy) profiles, and Systemic (SYS) subtypes and explored the association of these classification systems.

Key findings: The GOLD stages showed correlations with 15 metabolites, including lysophospholipids, oxylipins, and bile acids. KNGF profiles were linked to 13 metabolites, predominantly lysophospholipids, while SYS subtypes were associated with 9 metabolites, mainly oxylipins. A specific cluster of oxylipins, including HETEs and HDoHEs, was notably correlated to prognostic factors of COPD.

Significance: This study identified distinct metabolic patterns associated with GOLD stages, KNGF profiles, and SYS subtypes. Additionally, the findings indicate that 14-HDoHE/DHA may serve as a potential biomarker for COPD exacerbation and suggest possible therapeutic targets for COPD, including pathways involving lipoxygenases, G-protein coupled receptors, and the Farnesoid X receptor.

Keywords: COPD; GOLD stage; KNGF profile; Metabolomics; SYS subtype; Signaling lipids.