Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness
Author(s)
Type
Journal Article
Abstract
Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements. We collected and analyzed exhaled breath samples from 277 participants presenting acute cardiorespiratory exacerbations and aged-matched healthy volunteers. Topological data analysis phenotypes differentiated acute disease from health and acute cardiorespiratory exacerbation subtypes (acute heart failure, acute asthma, acute chronic obstructive pulmonary disease, and community-acquired pneumonia). A multibiomarker score (101 breath biomarkers) demonstrated good diagnostic sensitivity and specificity (≥80%) in both discovery and replication sets and was associated with all-cause mortality at 2 years. In addition, VOC biomarker scores differentiated metabolic subgroups of cardiorespiratory exacerbation. Louvain clustering of VOCs coupled with metabolite enrichment and similarity assessment revealed highly specific enrichment patterns in all acute disease subgroups, for example, selective enrichment of correlated C5-7 hydrocarbons and C3-5 carbonyls in heart failure and selective depletion of correlated aldehydes in acute asthma. This study identified breath VOCs that differentiate acute cardiorespiratory exacerbations and associated subtypes and metabolic clusters of disease-associated VOCs.
Date Issued
2022-11-16
Date Acceptance
2022-11-01
Citation
Science Translational Medicine, 2022, 14 (671), pp.1-14
ISSN
1946-6234
Publisher
American Association for the Advancement of Science
Start Page
1
End Page
14
Journal / Book Title
Science Translational Medicine
Volume
14
Issue
671
Copyright Statement
Copyright© 2022The Authors,somerightsreserved;exclusive licenseeAmericanAssociationfor the Advancementof Science.No claimto originalU.S.GovernmentWorks. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Translational Medicine on 14, 16 November 2022, DOI: https://doi.org/10.1126/scitranslmed.abl5849
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000890052400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Cell Biology
CELLS
Life Sciences & Biomedicine
LUNG-CANCER
Medicine, Research & Experimental
Research & Experimental Medicine
Science & Technology
VOLATILE ORGANIC-COMPOUNDS
Publication Status
Published
Article Number
ARTN eabl5849
Date Publish Online
2022-11-16