Metabolomic Analysis of Disease Progression In Idiopathic Pulmonary Fibrosis and Interstitial Lung Diseases
Document Type
Conference Proceeding
Publication Date
2025
Publication Title
American Journal of Respiratory and Critical Care Medicine
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs) are characterized by progressive fibrosis and deteriorating lung function. Despite advancements in pharmacotherapy, these conditions remain clinically heterogeneous, with variable disease trajectories that challenge optimal patient management. This study aimed to distinguish metabolomic profiles between progressive and stable IPF/ILD subjects to identify individuals at high risk for disease progression.
Methods: This single-center prospective study enrolled (n=60) participants between December 2021 and October 2022. Participants were categorized as progressive or stable 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 associated with the disease.
Results: Among the 715 metabolites accurately quantified, 15 showed significantly different concentrations between progressive and stable IPF/ILD patients (False Discovery Rate [FDR] q < 0.05). Detailed analysis revealed distinct metabolic signatures associated with disease progression, characterized by significant high abundance in phosphatidylethanolamines (PE) and triacylglycerides (TG) species (FDR q < 0.05) in progressive IPF/ILD compared to stable IPF/ILD individuals. Pathway enrichment analysis comparing progressive versus stable IPF/ILD groups identified significant disruptions in glycerophospholipid metabolism (FDR q-value < 0.05), suggesting that these pathways may play a crucial role in disease progression. Conclusion: This study identifies specific metabolic signatures associated with IPF/ILD progression, particularly involving glycerophospholipid metabolism. The high abundance of PE and TG species in progressive IPF individuals suggest their potential utility for monitoring disease trajectory. These findings provide new insights into the metabolic changes accompanying disease progression in IPF/ILD and identify potential therapeutic targets.
Volume
211
First Page
A7641
Recommended Citation
Smith Z, Faizee F, Alnabulsi Z, Ashrafi N, Yilmaz A, Mimi RA, et al [ SF Graham, Nair GB] Metabolomic analysis of disease progression in idiopathic pulmonary fibrosis and interstitial lung diseases. Am J Respir Crit Care Med. 2025;211:A7641.doi:10.1164/ajrccm.2025.211.Abstracts.A7641
DOI
10.1164/ajrccm.2025.211.Abstracts.A7641
Comments
The American Thoracic Society (ATS) International Conference, May 16-21, 2025, San Francisco, CA.