Direct Detection of an Aspergillus fumigatus -specific Breath Volatile Organic Metabolite Profile for the Diagnosis of Invasive Aspergillosis

Ref ID: 19569

Author:

S Koo1,2,3*, HR Thomas1,3, SD Daniels1, P Rearden4, J Comolli4, LR Baden1,2,3, FM Marty1,2,3

Author address:

1Infectious Diseases, Brigham and Women’s Hospital, Boston, MA, USA
2Dana-Farber Cancer Institute, Boston, MA, USA
3Harvard Medical School, Boston, MA, USA
4Draper Laboratory, Cambridge, MA, USA

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Aspergillus fumigatus emits a complex bouquet of volatile organic compounds (VOC) in vitro,
distinctive from the VOC profile of other pathogenic mold species. A VOC profile of the terpene
and sesquiterpene compounds camphene, α – and β -pinene, limonene, α -bergamotene, and farnesene
is particularly characteristic of A. fumigatus in vitro and distinguishes A. fumigatus from other
pathogenic molds, including other Aspergillus species. We assessed whether we could discriminate
patients with invasive aspergillosis (IA) from patients without IA by directly detecting these volatile
metabolites of fungal origin in their breath.
Methods:
We collected tidal breath from patients with suspected invasive fungal disease (IFD) and concurrent
ambient air control samples onto thermal desorption traps designed to retain VOCs of diverse
size, boiling points, and polarity from November 2011 through September 2013. We used gas
chromatography-mass spectrometry to assess for Aspergillus fumigatus-specific VOCs in these
breath samples, minus ambient air.
Results:
Of 64 patients, 25 (39%) were female, 54 (84%) were patients with hematologic malignancy, 24 (38%)
were allogeneic stem-cell transplantation recipients, 8 (13%) were solid organ transplant recipients,
27 (42%) had prolonged neutropenia, 55 (86%) were receiving T-cell immunosuppressants and
12 (19%) corticosteroids. These characteristics were comparable in 34 patients with EORTC/MSG
proven (5) or probable (29) IA and 30 patients with nodular pneumonia caused by other IFD or other
infectious processes. While some of the volatile metabolites produced in vitro by A. fumigatus were
equally present in patients with or without IA (camphene, α – and β -pinene, limonene), a combination of
the sesquiterpenes farnesene and β -vatirenene and the farnesene derivative geranylacetone correctly
discriminated patients with IA from patients with other IFD or other infectious or inflammatory
pneumonias in 60/64 (94%) patients, with 94% sensitivity and 93% specificity (Figure). Aspergillus
niger, which has a distinct VOC profile from A. fumigatus in vitro, was ultimately identified as
the causal etiology of pneumonia in one of the IA patients who had no farnesene, β -vatirenene , or
geranylacetone in their breath sample. One patient with breath farnesene and geranylacetone was
initially classified as not having IA by EORTC/MSG criteria, but on autopsy was found to have
invasive pulmonary aspergillosis.
Conclusion:
In breath sampled from patients with suspected IFD, an Aspergillus fumigatus-specific VOC profile
of farnesene, β -vatirenene, and geranylacetone accurately and noninvasively discriminates clinically
comparable patients with IA from patients with other causes of pneumonia. NOTE: THIS ABSTRACT HAS BEEN SELECTED FOR ORAL PRESENTATION.

Abstract Number: 95

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

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