  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.
