Novel breath test helped identify invasive aspergillosis

DENVER – A novel breathalyzerlike test detected fungal gas metabolites in the breath of immunocompromised patients with suspected invasive aspergillosis, with excellent sensitivity and specificity, a single-center study demonstrated.

"We envision this work can be adapted to a rapid, noninvasive point-of-care detection system for real-time surveillance of patient breath for the emergence of aspergillosis and potentially for the diagnosis of lung infections caused by other fungal and bacterial pathogens," Dr. Sophia Koo said in an interview prior to a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"An urgent need" exists for better diagnostic tests for invasive aspergillosis, a life-threatening fungal pneumonia in immunocompromised patients, explained Dr. Koo of Harvard Medical School, Boston. Current diagnostic tests – respiratory tract cultures, serum and bronchoalveolar lavage for fungal antigen testing, and nucleic acid detection assays – "have significant limitations in their sensitivity and specificity, and the turnaround time of these assays in clinical practice is often days," she said.

Dr. Koo and her colleagues developed a new method to detect volatile fungal metabolites directly in patient breath. First, they defined the fungal volatile metabolite profile of Aspergillus fumigatus, the most common cause of invasive aspergillosis, in in vitro culture. Next, they used gas chromatography–mass spectrometry to detect those metabolites in the breath of 54 immunocompromised patients with suspected invasive aspergillosis pneumonia. Of those 54 patients, 29 ultimately had invasive aspergillosis, and 25 had other causes of pneumonia.

The breathalyzerlike test correctly identified 27 of 29 patients with invasive aspergillosis and 24 of 25 patients without invasive aspergillosis, for an overall diagnostic sensitivity of 93% and a diagnostic specificity of 96%.

"We were a bit surprised by how clearly we were able to discriminate patients with invasive aspergillosis from patients with other pneumonias using this approach," Dr. Koo noted. "When we made our initial plot of breath fungal volatile metabolites, clustered by patients with and without invasive aspergillosis, there was a clear line demarcating the two groups. We expected some differences in the fungal volatile metabolite profile in vitro and in vivo, with the overlay of the host-pathogen interaction, and we did indeed see some fungal metabolites in vivo that we did not see in any of our in vitro experiments."

While Dr. Koo described gas chromatography–mass spectrometry as "labor intensive," she characterized the findings of the current study as "easily translatable to a point of care platform for the detection of these fungal breath metabolites and potentially the diagnosis of other bacterial and fungal pneumonias at the bedside."

Dr. Koo acknowledged certain limitations of the study, including its single-center design and the fact that it will require validation in a larger cohort of patients.

The National Institutes of Health and the Harvard Catalyst/the Harvard Clinical and Translational Science Center Pilot Grant Program supported the study. The authors stated that they have no relevant financial conflicts.

[email protected]

DENVER – A novel breathalyzerlike test detected fungal gas metabolites in the breath of immunocompromised patients with suspected invasive aspergillosis, with excellent sensitivity and specificity, a single-center study demonstrated.

"We envision this work can be adapted to a rapid, noninvasive point-of-care detection system for real-time surveillance of patient breath for the emergence of aspergillosis and potentially for the diagnosis of lung infections caused by other fungal and bacterial pathogens," Dr. Sophia Koo said in an interview prior to a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"An urgent need" exists for better diagnostic tests for invasive aspergillosis, a life-threatening fungal pneumonia in immunocompromised patients, explained Dr. Koo of Harvard Medical School, Boston. Current diagnostic tests – respiratory tract cultures, serum and bronchoalveolar lavage for fungal antigen testing, and nucleic acid detection assays – "have significant limitations in their sensitivity and specificity, and the turnaround time of these assays in clinical practice is often days," she said.

Dr. Koo and her colleagues developed a new method to detect volatile fungal metabolites directly in patient breath. First, they defined the fungal volatile metabolite profile of Aspergillus fumigatus, the most common cause of invasive aspergillosis, in in vitro culture. Next, they used gas chromatography–mass spectrometry to detect those metabolites in the breath of 54 immunocompromised patients with suspected invasive aspergillosis pneumonia. Of those 54 patients, 29 ultimately had invasive aspergillosis, and 25 had other causes of pneumonia.

The breathalyzerlike test correctly identified 27 of 29 patients with invasive aspergillosis and 24 of 25 patients without invasive aspergillosis, for an overall diagnostic sensitivity of 93% and a diagnostic specificity of 96%.

"We were a bit surprised by how clearly we were able to discriminate patients with invasive aspergillosis from patients with other pneumonias using this approach," Dr. Koo noted. "When we made our initial plot of breath fungal volatile metabolites, clustered by patients with and without invasive aspergillosis, there was a clear line demarcating the two groups. We expected some differences in the fungal volatile metabolite profile in vitro and in vivo, with the overlay of the host-pathogen interaction, and we did indeed see some fungal metabolites in vivo that we did not see in any of our in vitro experiments."

While Dr. Koo described gas chromatography–mass spectrometry as "labor intensive," she characterized the findings of the current study as "easily translatable to a point of care platform for the detection of these fungal breath metabolites and potentially the diagnosis of other bacterial and fungal pneumonias at the bedside."

Dr. Koo acknowledged certain limitations of the study, including its single-center design and the fact that it will require validation in a larger cohort of patients.

The National Institutes of Health and the Harvard Catalyst/the Harvard Clinical and Translational Science Center Pilot Grant Program supported the study. The authors stated that they have no relevant financial conflicts.

[email protected]

DENVER – A novel breathalyzerlike test detected fungal gas metabolites in the breath of immunocompromised patients with suspected invasive aspergillosis, with excellent sensitivity and specificity, a single-center study demonstrated.

"We envision this work can be adapted to a rapid, noninvasive point-of-care detection system for real-time surveillance of patient breath for the emergence of aspergillosis and potentially for the diagnosis of lung infections caused by other fungal and bacterial pathogens," Dr. Sophia Koo said in an interview prior to a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"An urgent need" exists for better diagnostic tests for invasive aspergillosis, a life-threatening fungal pneumonia in immunocompromised patients, explained Dr. Koo of Harvard Medical School, Boston. Current diagnostic tests – respiratory tract cultures, serum and bronchoalveolar lavage for fungal antigen testing, and nucleic acid detection assays – "have significant limitations in their sensitivity and specificity, and the turnaround time of these assays in clinical practice is often days," she said.

Dr. Koo and her colleagues developed a new method to detect volatile fungal metabolites directly in patient breath. First, they defined the fungal volatile metabolite profile of Aspergillus fumigatus, the most common cause of invasive aspergillosis, in in vitro culture. Next, they used gas chromatography–mass spectrometry to detect those metabolites in the breath of 54 immunocompromised patients with suspected invasive aspergillosis pneumonia. Of those 54 patients, 29 ultimately had invasive aspergillosis, and 25 had other causes of pneumonia.

The breathalyzerlike test correctly identified 27 of 29 patients with invasive aspergillosis and 24 of 25 patients without invasive aspergillosis, for an overall diagnostic sensitivity of 93% and a diagnostic specificity of 96%.

"We were a bit surprised by how clearly we were able to discriminate patients with invasive aspergillosis from patients with other pneumonias using this approach," Dr. Koo noted. "When we made our initial plot of breath fungal volatile metabolites, clustered by patients with and without invasive aspergillosis, there was a clear line demarcating the two groups. We expected some differences in the fungal volatile metabolite profile in vitro and in vivo, with the overlay of the host-pathogen interaction, and we did indeed see some fungal metabolites in vivo that we did not see in any of our in vitro experiments."

While Dr. Koo described gas chromatography–mass spectrometry as "labor intensive," she characterized the findings of the current study as "easily translatable to a point of care platform for the detection of these fungal breath metabolites and potentially the diagnosis of other bacterial and fungal pneumonias at the bedside."

Dr. Koo acknowledged certain limitations of the study, including its single-center design and the fact that it will require validation in a larger cohort of patients.

The National Institutes of Health and the Harvard Catalyst/the Harvard Clinical and Translational Science Center Pilot Grant Program supported the study. The authors stated that they have no relevant financial conflicts.

[email protected]