Physiological modeling of isoprene dynamics in exhaled breath

TL;DR

This study develops a compartmental model to understand how isoprene levels in human breath change during exercise, linking breath measurements to systemic blood concentrations and suggesting an extrahepatic source.

Contribution

The paper introduces a novel compartmental model for isoprene dynamics in exhaled breath, highlighting the role of perfusion and potential extrahepatic sources during physical activity.

Findings

Breath isoprene variability is linked to increased perfusion during exercise.

The model indicates significant extrahepatic tissue contribution to isoprene levels.

Experimental data supports the compartmental description of isoprene dynamics.

Abstract

Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs. Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.