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

Abstract

Isothermal rebreathing has been proposed as an experimental technique for estimating the alveolar levels of hydrophilic volatile organic compounds (VOCs) in exhaled breath. Using the prototypic test compounds acetone and methanol, we demonstrate that the end-tidal breath profiles of such substances during isothermal rebreathing show a characteristic increase that contradicts the conventional pulmonary inert gas elimination theory due to Farhi. On the other hand, these profiles can reliably be captured by virtue of a previously developed mathematical model for the general exhalation kinetics of highly soluble, blood-borne VOCs, which explicitly takes into account airway gas exchange as a major determinant of the observable breath output. This model allows for a mechanistic analysis of various rebreathing protocols suggested in the literature. In particular, it predicts that the end-exhaled levels of acetone and methanol measured during free tidal breathing will underestimate the underlying alveolar concentration by a factor of up to 1.5. Moreover, it clarifies the discrepancies between in vitro and in vivo blood-breath ratios of hydrophilic VOCs and yields further quantitative insights into the physiological components of isothermal rebreathing and highly soluble gas exchange in general.

Background levels and diurnal variations of hydrogen cyanide in breath and emitted from skin

“…This has recently been demonstrated for acetone, which has a similar water air partition coefficient as HCN [37]. A way to measure alveolar HCN levels could be to combine nose breathing with the isothermal rebreathing sampling technique [38,39]. The emission from the skin was sampled before and after washing because it was noticed in exploratory tests that the skin emitted considerably less HCN for 2-3 hours after washing with water.…”

Physiological Modeling for Analysis of Exhaled Breath

“…Similarly, during hyperventilation breath acetone levels tend to increase, whereas a (slight) decrease might be expected from Equation (1.1) (due to a drastic rise of the ventilation-perfusion ratio). Further evidence for the inadequacy of classical pulmonary inert gas elimination theory in describing the blood-breath relationships of hydrophilic compounds can be derived from isothermal rebreathing experiments [30]. The heuristic intention leading to isothermal rebreathing is to create an experimental situation diminishing the influence of the wash-in/washout mechanisms discussed above.…”

“…Additionally, warming the rebreathing volume to body temperature will ensure a similar solubility of these VOCs in both regions of the pulmonary tract, alveoli and airways. End-tidal breath profiles of highly water soluble VOCs such as acetone and methanol may increase by a factor of up to 1.5 during isothermal rebreathing [30], until approaching a plateau value that corresponds to the underlying alveolar concentration. Again, this behavior sharply contrasts with the formalism underlying Equation (1.1).…”

Quantitative Analysis of VOCs in Exhaled Breath from Asian Volunteers: A Pilot Study

“…Human breath contains hundreds of VOCs in ppb (parts per billion (by volume)) levels that are associated with normal metabolism (e.g., ethanol, isoprene, propanone, and methanol), products of oxidative stress (e.g., propanedial and pentane), and with environmental and occupational exposures (e.g., trichloromethane and benzene) [7][8][9][10]. Measurements of specific VOCs of interest in exhaled breath would help in the development of health risk management strategies, leading to effective pollution prevention and early diagnosis for respiratory illnesses ensuring optimum lung health for Asian populations.…”

“…PTR-MS (Proton Transfer Reaction-Mass Spectrometry), characterized by very low detection limits and by a soft chemical ionization often producing the molecular ion only [13], has become very popular in recent years as an analytical technique for a wide range of applications [17,18]. Recent research reports by King et al, on PTRMS highlights the versatility of this online analytical technique for measurement of crucial VOCs in human volunteers under various conditions [10,17,18].…”