Department of Pharmacology, University of California, Irvine, Irvine, CA, United States.
Various compounds in present human breath have long been loosely associated with pathological states (including acetone smell in uncontrolled diabetes). Only recently, however, the precise measurement of exhaled volatile organic compounds (VOCs) and aerosolized particles was made possible at extremely low concentrations by advances in several analytical methodologies, described in detail in the international literature and each suitable for specific subsets of exhaled compounds. Exhaled gases may be generated endogenously (in the pulmonary tract, blood, or peripheral tissues), as metabolic by-products of human cells or colonizing micro-organisms, or may be inhaled as atmospheric pollutants; growing evidence indicates that several of these molecules have distinct cell-to-cell signaling functions. Independent of origin and physiological role, exhaled VOCs are attractive candidates as biomarkers of cellular activity/metabolism, and could be incorporated in future non-invasive clinical testing devices. Indeed, several recent studies reported altered exhaled gas profiles in dysmetabolic conditions and relatively accurate predictions of glucose concentrations, at least in controlled experimental conditions, for healthy and diabetic subjects over a broad range of glycemic values. Optimization of this methodology and validation in large-scale trials under a wider range of conditions is needed to determine its true potential to transition into practical clinical use.