The circulating metabolome in idiopathic pulmonary fibrosis (IPF)

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Introduction: The circulating metabolome, reflecting underlying cellular processes and biology, has not been characterised in patients with IPF. Aim: To determine differential metabolite expression in patients with IPF vs controls. Methods: Patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months (n=300) were drawn from the multicenter IPF-PRO Registry. Controls (n=100) without known lung disease were of similar age and sex distribution. Metabolites (408 in 11 major groups) were quantified using the Absolute IDQ p400HR kit. Of 398 metabolites detected, 303 were carried forward to analysis. Data were log2 transformed and linear regression used to compare metabolite expression in IPF vs control groups. Results: Patients with IPF were predominantly male (74.3%), former smokers (67.3%), with a median age of 70. Median (Q1, Q3) % predicted FVC and DLCO were 69.7 (61.0, 80.2) and 40.6 (31.7, 49.4), respectively. 229 metabolites were differentially expressed in the IPF vs. control group based on p-values corrected to control the false discovery rate at 5%, with 79 having a |log2FC|≥0.585 and 40 having a |log2FC|≥1. The top 40 metabolites that were differentially expressed came from 5 major groups (Figure). Conclusions: IPF associates with a distinct circulating metabolome. Further analysis of the IPF metabolome might aid the development of diagnostic biomarkers or the definition of novel disease endotypes.

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