Lipid biomarkers for differentiating asthma-COPD overlap: Insights from LC-MS-based lipidomics

Asthma-COPD overlap (ACO) is a complex clinical entity that combines features of both asthma and COPD. Patients with ACO tend to have more frequent exacerbations, faster decline in lung function, poorer quality of life, and increased hospital admissions. Lipids play a central role in airway inflammation, immune responses, and maintenance of lung function. Investigating lipid metabolism could enhance understanding of ACO pathophysiology and facilitate identification of potential disease-specific lipid biomarkers.

This study aimed to compare serum lipid profiles of ACO, asthma, and COPD patients and identify lipid markers that distinguish ACO from these related pulmonary disorders.

Using liquid chromatography-mass spectrometry (LC-MS)-based lipidomics, we explored serum lipid profiles of ACO, asthma, and COPD patients. Multivariate and univariate analyses were performed to identify distinct lipid signatures across the disease groups.

22 lipid classes comprising 1185 annotated lipid species were identified. Multivariate models demonstrated clear separation between ACO vs. asthma and ACO vs. COPD groups, with several hexosylceramides (HCER) emerging as consistently altered species. Among these, HCER(d18:0/24:1) + H and HCER(d18:0/20:0) + H showed high AUC values in differentiating ACO from asthma and COPD. A combined clinico-lipidomic Random Forest model demonstrated good classification performance. Notably, these HCERs correlated inversely with the lung function parameters, FEV₁ and FEV₁/FVC of ACO patients.

Compared with both asthma and COPD, ACO is characterized by distinct changes in serum lipid profiles, particularly involving HCERs. While these lipids show potential as discriminatory markers, this study is exploratory in nature and requires validation in larger, independent cohorts.