ORCID
- Wilde, Michael: 0000-0003-0726-890X
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.
DOI
10.1126/scitranslmed.abl5849
Publication Date
2022-11-16
Publication Title
Science Translational Medicine
ISSN
1946-6234
Embargo Period
2022-11-19
Organisational Unit
School of Geography, Earth and Environmental Sciences
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Wilde, M. J., Ibrahim, W., Cordell, R., Richardson, M., Free, R., Zhao, B., Singapuri, A., Hargadon, B., Gaillard, E., Suzuki, T., Ng, L., Coats, T., Thomas, P., Monks, P., Brightling, C., Greening, N., & Siddiqui, S. (2022) 'Visualisation of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness', Science Translational Medicine, . Available at: https://doi.org/10.1126/scitranslmed.abl5849
