Metabolomic profiling reveals distinct lipid signatures in progressive versus stable fibrotic lung disease

To compare the metabolomic profile differences between ILD (interstitial lung disease) and chronic obstructive pulmonary disease (COPD) controls, and to distinguish profiles between progressive and stable idiopathic pulmonary fibrosis (IPF)/ILD subjects.

This single-center prospective study enrolled n = 71 (progressive IPF/ILD: n = 33, stable IPF/ILD: n = 27, COPD: n = 11) participants between December 2021 and October 2022. Metabolite quantification was performed using the liquid chromatography-mass spectrometry (LC-MS platform), and nuclear magnetic resonance spectroscopy (¹H NMR). Further, pathway enrichment analysis was performed to identify biochemical pathways associated with the disease.

715 metabolites were accurately quantified to investigate (a) differences between the combined groups of stable and progressive idiopathic pulmonary fibrosis IPF/ILD and COPD controls, and (b) differences between progressive IPF/ILD and stable IPF/ILD controls. The most notable metabolites distinguishing fibrotic lung disease (both stable and progressive IPF/ILD) from COPD were glycerolipids (GL). Enrichment analysis of IPF/ILD versus COPD revealed significant disruptions in lipid metabolic pathways, particularly glycerophospholipids, and sphingolipids (false discovery rate FDR q-value < 0.05). In addition, significant disruptions in TG species were found in progressive IPF/ILD with enrichment analysis revealing dysregulation of metabolic pathways associated with glycerophospholipids (FDR q-value < 0.05).

These findings emphasize the dysregulation of lipid metabolism in fibrotic lung diseases, involving glycerolipids, glycerophospholipids, and sphingolipids. The distinct lipid alterations identified through metabolomic profiling provide valuable insight into lipid metabolism in IPF/ILD, warranting further research to explore their potential as biomarkers.