Some crucial principles of exhaled breath volatile analysis

This review addresses several important confounding factors that are often overlooked in the analysis of volatiles contained in exhaled breath, which, if ignored, will significantly limit the interpretation of volatile data from exhaled breath and thus prevent meaningful outcomes. Crucial confounding factors that tend to be neglected are those that influence the alveolar volatile concentrations according to the Farhi equation, namely cardiac output, alveolar ventilation, blood:air partition coefficients and mixed-venous blood volatile concentrations. Another potential confounding factor is associated with the contributions of volatiles produced in the oral cavity through microbial activity. In addition, the concentration of an exhaled breath volatile will be affected if that volatile is also present in the ambient inhaled air. The purpose of this review is to show how these confounding factors can be accounted for. We will demonstrate how mathematical modeling and an understanding of the Farhi equation aid in the interpretation of the exhaled breath volatile concentration measurements. We will discuss the limitations of the alveolar gradient method used to determine the effects of inhaled volatiles. An alternative method is presented that correctly allows for any inhaled volatile contribution to the exhaled concentration of that volatile. The review concludes with suggested recommendations that, if adopted, will improve the quality of breath data leading to an improved interpretation of exhaled volatiles.