Abstract
On-line analysis of exhaled breath offers insight into a person's metabolism without the need for sample preparation or sample collection. Due to its noninvasive nature and the possibility to sample continuously, the analysis of breath has great clinical potential. The unique features of this technology make it an attractive candidate for applications in medicine, beyond the task of diagnosis. We review the current methodologies for on-line breath analysis, discuss current and future applications, and critically evaluate challenges and pitfalls such as the need for standardization. Special emphasis is given to the use of the technology in diagnosing respiratory diseases, potential niche applications, and the promise of breath analysis for personalized medicine. The analytical methodologies used range from very small and low-cost chemical sensors, which are ideal for continuous monitoring of disease status, to optical spectroscopy and state-of-the-art, high-resolution mass spectrometry. The latter can be utilized for untargeted analysis of exhaled breath, with the capability to identify hitherto unknown molecules. The interpretation of the resulting big data sets is complex and often constrained due to a limited number of participants. Even larger data sets will be needed for assessing reproducibility and for validation of biomarker candidates. In addition, molecular structures and quantification of compounds are generally not easily available from on-line measurements and require complementary measurements, for example, a separation method coupled to mass spectrometry. Furthermore, a lack of standardization still hampers the application of the technique to screen larger cohorts of patients. This review summarizes the present status and continuous improvements of the principal on-line breath analysis methods and evaluates obstacles for their wider application.
Highlights
On-line analysis of exhaled breath, sometimes called "real-time" or "direct" breath analysis, has gained a lot of momentum in recent years, and could in the future become the method of choice for some applications in medical diagnosis and personalized medicine
1 Direct, i.e., non-separative mass spectrometry methods for non-invasive diagnostics based on volatile organic compounds (VOCs) were reviewed by Casas-Ferreira et al 2, Giannoukos et al summarized applications for security and biodiagnostics 3 and Ahmed et al covered the analysis of exhaled volatile organics that play a role in infection. 4
VOCs can either be endogenous, i.e., they arise from the respiratory tract or they are of systemic origin after passing the bloodair-barrier, or VOCs can be of exogenous origin, in which case they originate from the environment and are inhaled and exhaled without alteration
Summary
On-line analysis of exhaled breath, sometimes called "real-time" or "direct" breath analysis, has gained a lot of momentum in recent years, and could in the future become the method of choice for some applications in medical diagnosis and personalized medicine. Breath is available in nearly unlimited quantities, its analysis presents no burden to the subject being measured, and its on-line analysis allows continuous monitoring of metabolic health, disease progression, and medication in short time intervals This approach might become indispensable in certain critical situations, e.g., in the emergency room, for correct treatment of a dangerous infection such as pneumonia, when consumption of potentially dangerous party drugs must be ascertained, in doping control, or in other situations where immediate action is necessary. On-line analysis of exhaled breath could potentially reveal novel biomarkers for diseases, allow disease phenotyping, might become an inexpensive replacement for established tests, permit bedside or even home monitoring, and allow cost-effective and frequent checks of disease progression, effectiveness of a therapy, and adherence to medication It could open up completely new applications, e.g., diagnosis of asthma in young children or chronobiology where continuous sampling is required (e.g. sleep studies). Wallace, and Pleil reviewed methods and instrumentation for analyzing exhaled gas-phase, condensate, and aerosols for use in clinical and environmental health applications. 1 Direct, i.e., non-separative mass spectrometry methods for non-invasive diagnostics based on volatile organic compounds (VOCs) were reviewed by Casas-Ferreira et al 2, Giannoukos et al summarized applications for security and biodiagnostics 3 and Ahmed et al covered the analysis of exhaled volatile organics that play a role in infection. 4
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