Metabolomic Profiling Reveals Distinct and Common Biological Pathways in COPD and IPF

Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic respiratory diseases with distinct pathologies but also shared risk factors, such as age and smoking. While genetic studies have identified five shared loci with opposite effects for both diseases, their downstream consequences remain unclear. To explore this, we performed untargeted metabolomic profiling on plasma samples from 1,507 individuals in the TOPMed initiative, including 480 COPD, 219 IPF, and 361 control subjects. Logistic regression identified 248 metabolites significantly associated with COPD, including alterations in steroid hormone biosynthesis, tryptophan catabolism, and sphingolipid metabolism. For IPF, 133 significant metabolites were identified, with changes in steroid hormone biosynthesis and polyamine metabolism. Additionally, 39 metabolites differed between COPD and IPF. These findings highlight distinct and overlapping metabolic pathways in COPD and IPF, offering insights for potential therapeutic targets.