Breath Test May Diagnose Fungal Pneumonia

Beth Skwarecki

October 29, 2014

A chemical signature of Aspergillus fumigatus infection can be detected in patients' breath, according to a study published online October 23 in Clinical Infectious Diseases.

"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," write Sophia Koo, MD, from the Division of Infectious Diseases at Brigham and Women's Hospital in Boston, Massachusetts, and colleagues.

Fungal infections including invasive aspergillosis (IA) often occur in patients who have had stem cell or organ transplants or who have hematologic cancers. The mortality rate for IA is 25% or more. At this time, the most definitive tests are invasive, including lung biopsy.

The new study involved 64 patients from Brigham and Women's Hospital and the Dana-Farber Cancer Institute, also in Boston, who were identified as having suspected cases of IA. According to later diagnosis, 34 of these patients had proven or probable IA, 10 had proven or probable cases of other types of fungal disease, and 20 had other or unknown causes of pneumonia.

The breath test required 4 minutes of breathing into a breath sampling machine, which the investigators report was well tolerated even among patients who were short of breath or who required supplemental oxygen. At the same time, the investigators took samples of the ambient air in the patient's room.

Four chemical compounds were found in the breath of patients with IA, but not in other patients. These included two sesquiterpenes that had been observed in in vitro tests as being unique to A fumigatus.

The four-compound signature correctly identified all five patients with proven IA (whose samples all grew A fumigatus in culture), all 21 who were considered to have "probable" IA based on positive tests for galactomannan, and six of seven patients who grew A fumigatus from respiratory tract culture. The sensitivity was 94% (95% confidence interval, 81% - 98%), and the specificity was 93% (95% confidence interval, 79% - 98%).

The investigators refer to their test as a proof of concept, writing that further research should focus on finding a relationship between the breath signature and the size of lesions and on distinguishing infection from chronic colonization.

"I really do applaud the authors for looking to find another noninvasive rapid test for identifying pulmonary aspergillosis. This is something that leads to a high rate of mortality, and anything we can use to diagnose it earlier is valuable," Erika Lease, MD, medical director of the lung transplant program at the University of Washington in Seattle, told Medscape Medical News. Dr Lease, who was not involved in the study, noted that existing biomarker tests for fungal antigens galactomannan and (1→3)-β-D-glucan do not always perform well in patients with solid organ transplants, possibly because of differences in their immune response. Although this means that new noninvasive tests are especially needed for those patients, she also cautions that because only eight of the 64 subjects in this study had had solid organ transplants, further research on the breath test should consider whether it works as well for organ transplant patients as for the other patients tested.

This work was supported by the Harvard Catalyst Pilot Grant Program and the National Institute of Allergy and Infectious Diseases. Brigham and Women's Hospital and the Charles Stark Draper Laboratory have filed a patent based in part on this work. One coauthor has reported receiving grant support from Astellas and WHISCON and consulting honoraria from Astellas, WHISCON, and Merck and has served as a board member for Astellas. The other authors and Dr Lease have disclosed no relevant financial relationships.

Clin Infect Dis. Published online October 23, 2014. Abstract

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