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Sci Transl Med

Title:		Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness
Author(s):		Ibrahim W; Wilde MJ; Cordell RL; Richardson M; Salman D; Free RC; Zhao B; Singapuri A; Hargadon B; Gaillard EA; Suzuki T; Ng LL; Coats T; Thomas P; Monks PS; Brightling CE; Greening NJ; Siddiqui S; Consortium E; Munton R; Le Quesne J; Goodall AH; Pandya HC; Reynolds JC; Clokie MRJ; Samani NJ; Barer MR; Shaw JA;
Address:		"Department of Respiratory Sciences, University of Leicester, Leicester LE1 7RH, UK. School of Chemistry, University of Leicester, Leicester LE1 7RH, UK. School of Geography, Earth and Environmental Sciences, University of Plymouth, Plymouth PL4 8AA, UK. Department of Chemistry, Loughborough University, Loughborough LE11 3TT, UK. Leverhulme Centre for Demographic Science, University of Oxford, Oxford OX1 1JD, UK. Nuffield College, University of Oxford, Oxford OX1 1NF, UK. Department of Cardiovascular Sciences, University of Leicester, Cardiovascular Research Center, Glenfield General Hospital, Leicester LE3 9QP, UK. Institute of Medical Science, University of Tokyo Shirokanedai, Minato-ku 4-6-1 108-8639, Tokyo, Japan. Emergency Medicine Academic Group, Department of Cardiovascular Sciences, University of Leicester, University Road, Leicester LE1 7RH, UK. National Heart and Lung Institute, Imperial College, London SW3 6LY UK"
Journal Title:		Sci Transl Med
Year:		2022
Volume:		20221116
Issue:		671
Page Number:		eabl5849 -
DOI:		10.1126/scitranslmed.abl5849
ISSN/ISBN:		1946-6242 (Electronic) 1946-6234 (Print) 1946-6234 (Linking)
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"
Keywords:		Humans Breath Tests *Volatile Organic Compounds/analysis Acute Disease Dyspnea/diagnosis *Asthma/diagnosis Biomarkers/metabolism *Heart Failure/diagnosis;
Notes:		"MedlineIbrahim, Wadah Wilde, Michael J Cordell, Rebecca L Richardson, Matthew Salman, Dahlia Free, Robert C Zhao, Bo Singapuri, Amisha Hargadon, Beverley Gaillard, Erol A Suzuki, Toru Ng, Leong L Coats, Tim Thomas, Paul Monks, Paul S Brightling, Christopher E Greening, Neil J Siddiqui, Salman Munton, Rachel Le Quesne, John Goodall, Alison H Pandya, Hitesh C Reynolds, James C Clokie, Martha R J Samani, Nilesh J Barer, Michael R Shaw, Jacqueline A eng DH_/Department of Health/United Kingdom MC_PC_19043/MRC_/Medical Research Council/United Kingdom 204801/WT_/Wellcome Trust/United Kingdom PDF-2017-10-052/DH_/Department of Health/United Kingdom G0601369/MRC_/Medical Research Council/United Kingdom MR/N005880/1/MRC_/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't 2022/11/17 Sci Transl Med. 2022 Nov 16; 14(671):eabl5849. doi: 10.1126/scitranslmed.abl5849. Epub 2022 Nov 16"