Physiological Modeling for Analysis of Exhaled Breath

Due to its broad scope and applicability, breath gas analysis holds great promise as a versatile framework for general bio-monitoring applications. As a biochemical probe, volatile organic compounds (VOCs) in exhaled breath are unique in the sense that they can provide both non-invasive and continuous information on the metabolic and physiological state of an individual. Apart from diagnostics and therapy control, this information might potentially be used for dynamic assessments of normal physiological function (e.g., by a stress test on a cycle ergometer, in an intra-operative setting, or in a sleep lab), pharmacodynamics (drug testing) or for quantifying body burden in response to environmental exposure (e.g., in occupational health) [3, 4, 2, 13, 46, 39, 44, 5]. Furthermore, as has been impressively demonstrated in the Nobel prize-winning work of Furchgott, Ignarro and Murad on the small inorganic molecule nitric oxide, trace gases can actively participate in the regulation of physiological events [23, 10]. This renders breath VOCs as an intriguing tool for examining more fundamental endogenous processes. While sufficiently accurate and fast instrumental techniques are vital for fully exploiting this huge potential, also several methodological issues need to be addressed before breath gas analysis can become the “new blood test”. Specifically, a crucial yet underestimated aspect of breath gas analysis concerns the blood-gas kinetics of the VOCs under scrutiny as well as their systemic distribution and physiological flow within the human body. Much can be learnt in this context from the cumbersome development of the nitric oxide breath test, which nowadays ranks among the most successful breath tests based on an endogenous compound [3]. This paradigmatic example shows that a purely explorative search for VOC biomarkers is not sufficient: in order to make breath tests operational, a thorough quantitative understanding of the underlying gas exchange mechanisms and their sensitivity with respect to physiological factors is