ABSTRACT

Respiratory bacterial, fungal, and viral infections can lead to substantial morbidity and mortality in people with underlying lung diseases, but may also cause problems for healthy adults. Although some rapid tests are available, they lack accuracy to be widely helpful and rely on direct pathogen identification. However, it appears that upper respiratory infections (URIs) may be non-invasively diagnosed by analyzing exhaled breath for specific host-response-to-infection metabolites along with metabolites from microorganisms themselves. Exhaled breath contains thousands of volatile organic compounds (VOCs) and inflammatory mediated markers. While past phenomenological studies have associated specific breath chemicals to specific diseases, there is no mechanistic framework in place to predict or understand how these biomarkers relate to overall health status. We propose 106that upon infection, species- and strain-specific cascades of intracellular signaling mechanisms are initiated that have metabolic end points released into exhaled human breath. By examining host-response to infection and metabolites generated from microorganisms themselves, we can build a “bottom-up” model of breath metabolites to understand better how they are generated and released in the human body.