Breath analysis for respiratory infections

Davis, Cristina E.; Hill, Jane E.; Frank, Matthias; McCartney, Mitchell M.; Schivo, Michael; Bean, Heather D.

doi:10.1016/b978-0-12-819967-1.00021-9

Cited by 8 publications

(13 citation statements)

References 28 publications

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“…Exhaled breath vapor is the collection of gas-phase compounds, including respiratory gases like O 2 , CO 2 , and NO, but also hundreds of volatile organic compounds (VOCs) known as the breath volatilome 9 . While exogenous compounds are the result of inspiring VOCs from the room or environment, endogenous compounds derive from metabolic processes and can reflect imbalances due to injury or disease 10 .…”

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confidence: 99%

Predominant SARS-CoV-2 variant impacts accuracy when screening for infection using exhaled breath vapor

et al. 2022

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Background New technologies with novel and ambitious approaches are being developed to diagnose or screen for SARS-CoV-2, including breath tests. The US FDA approved the first breath test for COVID-19 under emergency use authorization in April 2022. Most breath-based assays measure volatile metabolites exhaled by persons to identify a host response to infection. We hypothesized that the breathprint of COVID-19 fluctuated after Omicron became the primary variant of transmission over the Delta variant. Methods We collected breath samples from 142 persons with and without a confirmed COVID-19 infection during the Delta and Omicron waves. Breath samples were analyzed by gas chromatography-mass spectrometry. Results Here we show that based on 63 exhaled compounds, a general COVID-19 model had an accuracy of 0.73 ± 0.06, which improved to 0.82 ± 0.12 when modeling only the Delta wave, and 0.84 ± 0.06 for the Omicron wave. The specificity improved for the Delta and Omicron models (0.79 ± 0.21 and 0.74 ± 0.12, respectively) relative to the general model (0.61 ± 0.13). Conclusions We report that the volatile signature of COVID-19 in breath differs between the Delta-predominant and Omicron-predominant variant waves, and accuracies improve when samples from these waves are modeled separately rather than as one universal approach. Our findings have important implications for groups developing breath-based assays for COVID-19 and other respiratory pathogens, as the host response to infection may significantly differ depending on variants or subtypes.

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confidence: 99%

Predominant SARS-CoV-2 variant impacts accuracy when screening for infection using exhaled breath vapor

et al. 2022

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“…It may be of clinical or epidemiological interest to differentiate coccidioidomycosis from other fungal pneumonias such as aspergillosis, blastomycosis, histoplasmosis, or cryptococcosis. Previous studies have shown that bacterial lung pathogens have unique and reproducible volatilomes that can be used to detect and identify organisms at the genus, species, or strain level ( 11 ), and therefore, differentiating fungal pneumonias is feasible.…”

Section: Discussionmentioning

confidence: 99%

“…Breath-based diagnostics are a promising novel approach for diagnosing respiratory infections. Numerous in vitro studies have demonstrated that bacterial and fungal respiratory pathogens have unique volatile metabolome (or volatilome) signatures that can be used to differentiate and identify them to the genus, species, and strain levels ( 11 ). Thus far, relatively few studies have specifically focused on identifying breath biomarkers for fungal lung diseases.…”

Section: Introductionmentioning

confidence: 99%

Life Cycle Dominates the Volatilome Character of Dimorphic Fungus Coccidioides spp.

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et al. 2021

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Valley fever (coccidioidomycosis) is an endemic fungal pneumonia of the North and South American deserts. The causative agents of Valley fever are the dimorphic fungi Coccidioides immitis and C. posadasii, which grow as mycelia in the environment and as spherules within the lungs of vulnerable hosts. Current diagnostics for Valley fever are severely lacking due to poor sensitivity and invasiveness, contributing to a 23-day median time to diagnosis, and therefore, new diagnostic tools are needed. We are working toward the development of a breath-based diagnostic for coccidioidomycosis, and in this initial study, we characterized the volatile metabolomes (or volatilomes) of in vitro cultures of Coccidioides. Using solid-phase microextraction (SPME) and comprehensive two-dimensional gas chromatography coupled to time of flight mass spectrometry (GC×GC-TOFMS), we characterized the volatile organic compounds (VOCs) produced by six strains of each species during mycelial or spherule growth. We detected a total of 353 VOCs that were at least 2-fold more abundant in a Coccidioides culture than in medium controls and found that the volatile metabolome of Coccidioides is more dependent on the growth phase (spherules versus mycelia) than on the species. The volatile profiles of C. immitis and C. posadasii have strong similarities, indicating that a single suite of Valley fever breath biomarkers can be developed to detect both species. IMPORTANCE Coccidioidomycosis, or Valley fever, causes up to 30% of community-acquired pneumonias in highly populated areas of the U.S. desert southwest where the disease is endemic. The infection is difficult to diagnose by standard serological and histopathological methods, which delays appropriate treatment. Therefore, we are working toward the development of breath-based diagnostics for Valley fever. In this study, we characterized the volatile metabolomes (or volatilomes) of six strains each of Coccidioides immitis and C. posadasii, the dimorphic fungal species that cause Valley fever. By analyzing the volatilomes during the two modes of growth of the fungus—mycelia and spherules—we observed that the life cycle plays a significant role in the volatiles produced by Coccidioides. In contrast, we observed no significant differences in the C. immitis versus C. posadasii volatilomes. These data suggest that life cycle, rather than species, should guide the selection of putative biomarkers for a Valley fever breath test.

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“…Breath screening would also reduce the number of patients that must undergo more invasive procedures, alleviating certain pressures and backlog in the healthcare system [ 2 ]. The concept of chemically profiling exhaled breath is not new but has certainly gained significant momentum [ 3 ]. Research has also been performed regarding the application of breathomics during the current urgency for COVID-19 diagnosis and in differentiating the disease from other respiratory infections [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Pilot Study on Exhaled Breath Analysis for a Healthy Adult Population in Hawaii

et al. 2021

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Fast diagnostic results using breath analysis are an anticipated possibility for disease diagnosis or general health screenings. Tests that do not require sending specimens to medical laboratories possess capabilities to speed patient diagnosis and protect both patient and healthcare staff from unnecessary prolonged exposure. The objective of this work was to develop testing procedures on an initial healthy subject cohort in Hawaii to act as a range-finding pilot study for characterizing the baseline of exhaled breath prior to further research. Using comprehensive two-dimensional gas chromatography (GC×GC), this study analyzed exhaled breath from a healthy adult population in Hawaii to profile the range of different volatile organic compounds (VOCs) and survey Hawaii-specific differences. The most consistently reported compounds in the breath profile of individuals were acetic acid, dimethoxymethane, benzoic acid methyl ester, and n-hexane. In comparison to other breathprinting studies, the list of compounds discovered was representative of control cohorts. This must be considered when implementing proposed breath diagnostics in new locations with increased interpersonal variation due to diversity. Further studies on larger numbers of subjects over longer periods of time will provide additional foundational data on baseline breath VOC profiles of control populations for comparison to disease-positive cohorts.

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Breath analysis for respiratory infections

Cited by 8 publications

References 28 publications

Predominant SARS-CoV-2 variant impacts accuracy when screening for infection using exhaled breath vapor

Predominant SARS-CoV-2 variant impacts accuracy when screening for infection using exhaled breath vapor

Life Cycle Dominates the Volatilome Character of Dimorphic Fungus Coccidioides spp.

Pilot Study on Exhaled Breath Analysis for a Healthy Adult Population in Hawaii

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