Abstract
The detection of chemical compounds in exhaled human breath presents an opportunity to determine physiological state, diagnose disease or assess environmental exposure. Recent advancements in metabolomics research have led to improved capabilities to explore human metabolic profiles in breath. Despite some notable challenges in sampling and analysis, exhaled breath represents a desirable medium for metabolomics applications, foremost due to its non-invasive, convenient and practically limitless availability. Several breath-based tests that target either endogenous or exogenous gas-phase compounds are currently established and are in practical and/or clinical use. This review outlines the concept of breath analysis in the context of these unique tests and their applications. The respective breath biomarkers targeted in each test are discussed in relation to their physiological production in the human body and the development and implementation of the associated tests. The paper concludes with a brief insight into prospective tests and an outlook of the future direction of breath research.
Highlights
Metabolomics is an emerging discipline that offers a promising opportunity to examine the human physiology in relation to different scenarios, from screening for disease, to targeting drug metabolism, or estimating the burden of environmental stressors; it thereby serves as a potential tool for objective diagnostics
The potential for exhaled breath to either detect this airborne virus directly or to diagnose infection is currently being investigated as a comfortable alternative to existing approaches that collect mucus secretions via nasopharyngeal or oropharyngeal swabs, or serological samples [249,250,251]
While no breath test has yet been developed that allows a reliable detection of the infection, studies have reported potential breath-borne volatile organic compounds (VOCs) biomarkers [252] or specific breathprints [253] for COVID-19, as well as evidence for tests using nanomaterial-based sensors [254]
Summary
The endogenous compounds present in breath derive from regular internal metabolic production, with either subsequent systemic circulation and transition into the gas-phase after passing the alveolar-blood capillary membranes in the lungs, or direct release into exhaled gas in the case of localised airways production [19,30]. The applications of endogenous compound-based breath tests that are currently implemented range from widespread routine use to highly specific settings. The most common test uses carbon dioxide, a by-product of cellular respiration, as a breath-borne marker to monitor breathing (e.g., in intensive care or sedated patients), whereas other tests target specific compounds for particular cases, e.g., nitric oxide in patients with asthma, or carbon monoxide in infants at risk of neonatal jaundice, demonstrating the prospects of breath tests based on a symptomatic approach. The Heartsbreath test for heart allograft rejection further shows the applicability of breath testing of multiple compounds as a screening procedure for adverse events. This section reviews the breath tests that utilise endogenous compounds, starting with the most common and widely implemented procedure
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