Metabolomic Signatures Linked to HRCT-defined Disease Phenotypes in Progressive and Stable Fibrotic 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 interstitial lung diseases (ILDs) are marked by lung fibrosis, with high-resolution computed tomography (HRCT) revealing characteristic radiographic patterns. This study aimed to integrate specific HRCT features and metabolomic profiles in progressive and stable IPF/ILD.
Methods: This single-center prospective study enrolled (n= 60) participants between December 2021 and October 2022, categorized as stable or progressive IPF/ILD per 2018 IPF guidelines. Further, we developed a novel HRCT grading system evaluating four key radiographic features (ground-glass opacity, reticulation, traction bronchiectasis, and honeycombing) across six lung zones. Each feature was scored on a semi-quantitative scale from 0 (absent) to 5 (very severe, >50% region affected). Then, the metabolomic profiling was conducted using the Biocrates Quant 500 XL assay on a liquid chromatography-mass spectrometry (LC-MS platform), and nuclear magnetic resonance spectroscopy (H NMR) platforms. Correlation analyses were performed to assess associations between the radiographic scoring and metabolomic profiles.
Results: Distinct metabolomic profiles emerged when comparing stable and progressive IPF/ILD radiographic phenotypes. In progressive disease with traction bronchiectasis, a low abundance of phosphatidylethanolamines (PE) and plasmalogens species (False Discovery Rate [FDR] q < 0.05) were observed; while triacylglycerols (TG) were significantly high abundant in stable disease with the same feature (FDR q < 0.05). Among individuals with honeycombing, TG species were in significant high abundance in stable disease (FDR q < 0.05), whereas sphingomyelins (SM) and ceramides (Cer) were abundant in progressors (FDR q < 0.05). Reticulation patterns showed similar findings to traction bronchiectasis and honeycombing, with high abundance of TG species in stable disease (FDR q < 0.05) and increased Cer and SM in progressive cases (FDR q < 0.05). In cases with ground-glass opacity, phospholipid variations were observed in multiple classes across both stable and progressive disease phenotypes, with TG demonstrating variable abundance (q < 0.05) between these groups.
Conclusion: Our findings highlight unique lipid signatures associated with HRCT phenotypes in fibrotic lung disease. Traction bronchiectasis and honeycombing patterns were associated with low abundance of PE and plasmalogens and high abundance of TG in stable disease, while progressive disease exhibited high abundance of SM and Cer. Further, reticulation patterns showed similar findings, with stable disease having high abundance of TG and progressive disease having high abundance of Cer and SM. Ground-glass opacity demonstrated variable abundance of TG between stable and progressive phenotypes.
Volume
211
Issue
A7743
Recommended Citation
Faizee F, Smith Z, Al-Katib S, Alnabulsi Z, Smielewski M, Graham SF et al [ Ashrafi N, Yilmaz A, Nair GB] Metabolomic signatures linked to hrct-defined disease phenotypes in progressive and stable fibrotic lung diseases. Am J Respir Crit Care Med. 2025;211:A7743.doi:10.1164/ajrccm.2025.211.Abstracts.A7743
DOI
10.1164/ajrccm.2025.211.Abstracts.A7743
Comments
The American Thoracic Society (ATS) International Conference, May 16-21, 2025, San Francisco, CA.