title: Physiological modeling of isoprene dynamics in exhaled breath.
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.
authors.affiliation: Breath Research Institute, Austrian Academy of Sciences, Rathausplatz 4, A-6850 Dornbirn, Austria.
authors.forename: Julian
authors.initials: J
authors.lastname: King
authors.forename: Helin
authors.initials: H
authors.lastname: Koc
authors.forename: Karl
authors.initials: K
authors.lastname: Unterkofler
authors.forename: Paweł
authors.initials: P
authors.lastname: Mochalski
authors.forename: Alexander
authors.initials: A
authors.lastname: Kupferthaler
authors.forename: Gerald
authors.initials: G
authors.lastname: Teschl
authors.forename: Susanne
authors.initials: S
authors.lastname: Teschl
authors.forename: Hartmann
authors.initials: H
authors.lastname: Hinterhuber
authors.forename: Anton
authors.initials: A
authors.lastname: Amann
mesh_terms: D000328:Adult; D001944:Breath Tests; D002070:Butadienes / Q000032:analysis*; D003198:Computer Simulation; D016552:Ergometry; D015444:Exercise / Q000502:physiology; D045853:Exhalation / Q000502:physiology*; D045782:Hemiterpenes / Q000032:analysis*; D006801:Humans; D008297:Male; D008954:Models, Biological; D010420:Pentanes / Q000032:analysis*; D011659:Pulmonary Gas Exchange; D015203:Reproducibility of Results
chemical_list: D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene