# Breath Volatile Metabolites for the Diagnosis of Coccidioidomycosis

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $214,171

## Abstract

Project Summary/Abstract: Coccidioidomycosis, caused by the highly infectious dimorphic fungi
Coccidioides posadasii and C. immitis, inflicts a heavy and rapidly growing burden of disease, with 150,000
new cases annually in the United States. Clinical symptoms of coccidioidomycosis are highly variable,
depending on the degree of exposure and robustness of host cell-mediated immunity – 40% of exposed
individuals develop an acute primary pulmonary coccidioidomycosis syndrome indistinguishable from regular
community-acquired pneumonia (CAP). While most of these patients eventually resolve their infection, 41-43%
are hospitalized for a median of 6 days, with disabling symptoms lasting several months. A subset of patients,
especially individuals with impaired cell-mediated immunity, progress to other, more severe coccidioidal
clinical syndromes, including disseminated infection, with high rates of morbidity and death. Although
coccidioidomycosis causes 30% of CAP cases in highly endemic regions, the clinical presentation is challenging
to differentiate from viral or bacterial CAP and available diagnostic tests have significant limitations, leading to
median diagnostic delays of 23-48 days, with many patients having delays lasting several months. Meanwhile,
patients seek medical care for their symptoms, with unnecessary hospitalizations, exposure to empiric broad-
spectrum antibiotics, laboratory tests, imaging, and invasive procedures. A critical barrier to improving clinical
outcomes in these patients is the lack of reliable diagnostic methods that identify coccidioidomycosis early in
the course of infection and distinguish it from other common infections with a similar clinical presentation.
Once coccidioidomycosis is diagnosed, it is also challenging to determine whether patients are responding to
antifungal therapy, due to slow resolution of symptoms and abnormal imaging and laboratory findings. To
address this unmet need, we propose a novel approach to the diagnosis of coccidioidomycosis based on
detection of fungal volatile metabolites in the breath. We will test the hypotheses that (a) patients with
coccidioidomycosis have unique breath metabolites that differentiate them from patients with other infections,
and (b) kinetics of these metabolites predict responses to antifungal therapy. We will: (1) identify breath
volatile metabolites that distinguish patients with coccidioidomycosis from those with similar clinical
syndromes, including CAP and other mycoses, and (2) examine the relationship between early changes in these
breath metabolites in patients with coccidioidomycosis treated with antifungal therapy and their clinical
outcome. Successful completion of these aims will lay the groundwork for a novel assay for the direct detection
of Coccidioides metabolism that can be coupled to a point-of-care gas sensor system for the rapid, bedside
identification of patients with coccidioidomycosis, reducing diagnostic delays, guiding appropriate initi...

## Key facts

- **NIH application ID:** 10312113
- **Project number:** 5R21AI156279-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Sophia Koo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $214,171
- **Award type:** 5
- **Project period:** 2020-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312113

## Citation

> US National Institutes of Health, RePORTER application 10312113, Breath Volatile Metabolites for the Diagnosis of Coccidioidomycosis (5R21AI156279-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10312113. Licensed CC0.

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