Metabolomic Insights Into Fibrotic Lung Disease Differentiation From Chronic Obstructive Pulmonary Disease
Document Type
Conference Proceeding
Publication Date
2025
Publication Title
American Journal of Respiratory and Critical Care Medicine
Abstract
Background: Fibrotic lung disease encompasses idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). We investigated distinct metabolic patterns between IPF/ILD and chronic obstructive pulmonary disease (COPD) to enhance our understanding of the underlying disease mechanisms related to disease progression.
Methods: This single-center prospective study enrolled (n=71) participants between December 2021 and October 2022. Participants were categorized as progressive or stable IPF/ILD based on the 2018 IPF guidelines. Metabolite quantification was performed using the biocrates Quant 500 XL assay, a liquid chromatography-mass spectrometry (LC-MS platform), and nuclear magnetic resonance spectroscopy (H NMR). Further, pathway enrichment analysis identified significantly disrupted biochemical pathways.
Results: Of the 715 metabolites accurately quantified, 59 showed significant differences between the combined IPF/ILD groups and COPD controls. The most distinctive metabolic signatures differentiating fibrotic lung disease from COPD were found in glycerolipids class (GL), particularly various triacylglycerol (TG) and diacylglycerol (DG) species (false discovery rate [FDR] q < 0.05). Enrichment analysis comparing IPF/ILD versus COPD revealed significant disruptions in lipid metabolic pathways, with notable alterations in glycerophospholipids and sphingolipids metabolism (FDR q-value < 0.05). These findings demonstrate clear metabolomic distinctions between fibrotic lung diseases and COPD, highlighting specific lipid metabolism pathways as key differentiators.
Conclusion: This study reveals distinct metabolomic signatures that effectively differentiate between ILD and COPD, particularly in lipid metabolism pathways. The identification of specific glycerolipid alterations provides mechanistic insights that might inform future biomarker development, potentially enabling early identification of patients at elevated risk for fibrotic lung disease progression. Further investigation of these metabolic pathways could lead to improved diagnostic tools and targeted therapeutic strategies.
Volume
211
First Page
A6147
Recommended Citation
Faizee F, Alnabulsi Z, Smith Z, Rojas O.R. Gomez, Yilmaz A et al [Graham SF, Nair GB] Metabolomic insights into fibrotic lung disease differentiation from chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2025;211: A6147. doi: 10.1164/ajrccm.2025.211.Abstracts.A6147
DOI
10.1164/ajrccm.2025.211.Abstracts.A6147
Comments
The American Thoracic Society (ATS) International Conference, May 16-21, 2025, San Francisco, CA.