A Breath Fungal Secondary Metabolite Signature to Diagnose Invasive Aspergillosis
Open accessAbstract
BACKGROUND: Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection. METHODS: Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples. RESULTS: The monoterpenes camphene, α- and β-pinene, and limonene, and the sesquiterpene compounds α- and β-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of α-trans-bergamotene, β-trans-bergamotene, a β-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%). CONCLUSIONS: In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia.
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A recent analysis of volatile organic compounds of A. fumigatus showed that β bergamotene was released in higher concentrations in vitro.
“A recent analysis of the volatile organic compounds of A. fumigatus showed that β bergamotene was released in higher concentrations in vitro and also was specifically identified in the exhaled breath condensates of patients with IA (146, 147).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [147]
β bergamotene was specifically identified in exhaled breath condensates of patients with IA.
“A recent analysis of the volatile organic compounds of A. fumigatus showed that β bergamotene was released in higher concentrations in vitro and also was specifically identified in the exhaled breath condensates of patients with IA (146, 147).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [147]
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- Authors
- Koo, S., Thomas, H. R., Daniels, S. D., Lynch, R. C., Fortier, S. M., Shea, M. M., Rearden, P., Comolli, J. C., Baden, L. R., & Marty, F. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Draper Laboratory (US)
- Corresponding author
- Koo, Sophia
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-22
- Volume
- 59
- Issue
- 12
- Pages
- 1733-1740
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC4311178
- OpenAlex
- W2171006576
- Cited by
- 153
- References
- 41
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 14 · 2023: 11 · 2022: 11 · 2021: 15 · 2020: 14 · 2019: 9 · 2018: 20 · 2017: 18 · 2016: 16 · 2015: 11 · 2014: 3
- FWCI
- 11.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- Charles Stark Draper Laboratory
- Harvard Catalyst (UL1-RR025758)
- Astellas Pharma
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (K23AI097225, R21AI085454)
- National Center for Research Resources (UL1RR025758)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Physical Sciences › Engineering › Biomedical Engineering › Advanced Chemical Sensor Technologies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Keywords
- invasive aspergillosis, Aspergillus fumigatus, breath analysis, secondary metabolites, monoterpenes, sesquiterpenes, non-invasive diagnosis, invasive fungal pneumonia, thermal desorption gas chromatography-mass spectrometry
- MeSH terms
- Limonene, Bicyclic Monoterpenes, Adult, Aged, Aspergillosis, Aspergillus fumigatus, Bridged Bicyclo Compounds, Female, Humans, Male, Gas Chromatography-Mass Spectrometry, Middle Aged, Prospective Studies, Sesquiterpenes, Terpenes, Monoterpenes, Cyclohexenes
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