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Isothermal rebreathing has been proposed as an experimental technique forestimating the alveolar levels of hydrophilic volatile organic compounds (VOCs)in exhaled breath. Using the prototypic test compound acetone we demonstratethat the end-tidal breath profiles of such substances during isothermalrebreathing show characteristics that contradict the conventional pulmonaryinert gas elimination theory due to Farhi. On the other hand, these profilescan reliably be captured by virtue of a previously developed mathematical modelfor the general exhalation kinetics of highly soluble, blood-borne VOCs, whichexplicitly takes into account airway gas exchange as major determinant of theobservable breath output.  This model allows for a mechanistic analysis of various rebreathing protocolssuggested in the literature. In particular, it clarifies the discrepanciesbetween in vitro and in vivo blood-breath ratios of hydrophilic VOCs and yieldsfurther quantitative insights into the physiological components of isothermalrebreathing.

A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds