Abstract
BackgroundQuantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.MethodsIn 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography–mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini–Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst.ResultsWe found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways.ConclusionsMetabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.