| Title: | A breath fungal secondary metabolite signature to diagnose invasive aspergillosis |
| Author(s): | Koo S; Thomas HR; Daniels SD; Lynch RC; Fortier SM; Shea MM; Rearden P; Comolli JC; Baden LR; Marty FM; |
| Address: | "Division of Infectious Diseases, Brigham and Women's Hospital Dana-Farber Cancer Institute Harvard Medical School, Boston. Division of Infectious Diseases, Brigham and Women's Hospital Harvard Medical School, Boston. Division of Infectious Diseases, Brigham and Women's Hospital. Draper Laboratory, Cambridge, Massachusetts" |
| ISSN/ISBN: | 1537-6591 (Electronic) 1058-4838 (Print) 1058-4838 (Linking) |
| Abstract: | "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, alpha- and beta-pinene, and limonene, and the sesquiterpene compounds alpha- and beta-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 alpha-trans-bergamotene, beta-trans-bergamotene, a beta-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" |
| Keywords: | Adult Aged Aspergillosis/*diagnosis/*metabolism Aspergillus fumigatus/*metabolism/*pathogenicity Bicyclic Monoterpenes Bridged Bicyclo Compounds/analysis Cyclohexenes/analysis Female Gas Chromatography-Mass Spectrometry Humans Limonene Male Middle Aged Mo; |
| Notes: | "MedlineKoo, Sophia Thomas, Horatio R Daniels, S David Lynch, Robert C Fortier, Sean M Shea, Margaret M Rearden, Preshious Comolli, James C Baden, Lindsey R Marty, Francisco M eng K23 AI097225/AI/NIAID NIH HHS/ R21 AI085454/AI/NIAID NIH HHS/ UL1 RR025758/RR/NCRR NIH HHS/ UL1 RR 025758/RR/NCRR NIH HHS/ Research Support, N.I.H., Extramural 2014/10/25 Clin Infect Dis. 2014 Dec 15; 59(12):1733-40. doi: 10.1093/cid/ciu725. Epub 2014 Oct 22" |
