EMBARGOED UNTIL: Tuesday, September 10, 12:00 PM MDT
(Session 23, Paper M-219)
Brigham & Women’s Hosp., Boston, MA, United States
Invasive aspergillosis is a common and often severe fungal infection that affects immunocompromised patients, particularly cancer and transplant patients. While early diagnosis and treatment reduce the severity of this infection, current diagnostic tests for invasive aspergillosis are limited, and diagnosis is often difficult until the infection is well-established. Many patients still require a biopsy procedure for diagnosis.
We developed a novel, noninvasive approach to the diagnosis of invasive aspergillosis using a Breathalyzer-like test for the detection of fungal gas metabolites in patient breath. By looking for gas molecules of fungal origin in the breath of immunocompromised patients with suspected invasive aspergillosis, we were able to distinguish patients with invasive aspergillosis accurately from patients with other causes of pneumonia. This breath test has the potential to improve the care of immunocompromised patients by allowing the rapid, noninvasive, and accurate diagnosis of invasive aspergillosis and prompt administration of antifungal medications to patients who have this infection.
This research was performed by Sophia Koo, MD, Horatio R. Thomas, AB, Preshious Rearden, PhD, James Comolli, PhD, Lindsey R. Baden, MD, and Francisco M. Marty, MD of Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, MA, and the Charles Stark Draper Laboratory in Cambridge, MA. This work was conducted with support from the National Institutes of Health (R21 AI085454, K23 AI097225) and the Harvard Catalyst│The Harvard Clinical and Translational Science Center Pilot Grant program (8UL1TR000170-05). Findings from this research will be presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in Denver, CO, on September 10, 2013.
We previously demonstrated that Aspergillus fumigatus, the most common cause of mold infections in immunocompromised patients, releases a distinctive set of gas molecules in in vitro cultures that distinguish it from other fungal species. In this study, we assessed whether we could identify these gas molecules in the breath of patients with Aspergillus pneumonia. We collected breath from 54 immunocompromised patients with suspected invasive aspergillosis, 29 who ultimately had invasive aspergillosis and 25 who had other causes of pneumonia. Using gas chromatography-mass spectrometry, we analyzed all organic gas metabolites in each breath sample, and found that a combination of the gas molecules farnesene, -vatirenene, and the farnesene derivative cis-geranylacetone correctly classified 27 of 29 patients with invasive aspergillosis and 24 of 25 patients without invasive aspergillosis, for an overall diagnostic accuracy of 94%.
This novel diagnostic breath test has practical applications for the clinical care of immuncompromised patients. We envision that the technology can be adapted to a simple, rapid, bedside breath gas detection system for real-time patient breath surveillance for this pattern of fungal metabolites, which may allow for earlier diagnosis of invasive aspergillosis than currently possible and ultimately, better patient outcomes.