25 research outputs found
A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds
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 compound acetone we demonstrate
that the end-tidal breath profiles of such substances during isothermal
rebreathing show characteristics that contradict 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 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 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.Comment: 21 page
Modeling-based determination of physiological parameters of systemic VOCs by breath gas analysis, part 2
In a recent paper we presented a simple two compartment model which describes
the influence of inhaled concentrations on exhaled breath concentrations for
volatile organic compounds (VOCs) with small Henry constants. In this paper we
extend this investigation concerning the influence of inhaled concentrations on
exhaled breath concentrations for VOCs with higher Henry constants.
To this end we extend our model with an additional compartment which takes
into account the influence of the upper airways on exhaled breath VOC
concentrations
Modeling-based determination of physiological parameters of systemic VOCs by breath gas analysis: a pilot study
In this paper we develop a simple two compartment model which extends the
Farhi equation to the case when the inhaled concentration of a volatile organic
compound (VOC) is not zero. The model connects the exhaled breath concentration
of systemic VOCs with physiological parameters such as endogenous production
rates and metabolic rates. Its validity is tested with data obtained for
isoprene and inhaled deuterated isoprene-D5.Comment: 16 page
Physiological modeling of isoprene dynamics in exhaled breath
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.Comment: 14 page
Modeling of breath methane concentration profiles during exercise on an ergometer
We develop a simple three compartment model based on mass balance equations
which quantitatively describes the dynamics of breath methane concentration
profiles during exercise on an ergometer. With the help of this model it is
possible to estimate the endogenous production rate of methane in the large
intestine by measuring breath gas concentrations of methane.Comment: 17 pages, 4 figure
Physiological modeling of isoprene dynamics in exhaled breath
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.Comment: 14 page
A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone
Recommended standardized procedures for determining exhaled lower respiratory
nitric oxide and nasal nitric oxide have been developed by task forces of the
European Respiratory Society and the American Thoracic Society. These
recommendations have paved the way for the measurement of nitric oxide to
become a diagnostic tool for specific clinical applications. It would be
desirable to develop similar guidelines for the sampling of other trace gases
in exhaled breath, especially volatile organic compounds (VOCs) which reflect
ongoing metabolism. The concentrations of water-soluble, blood-borne substances
in exhaled breath are influenced by: (i) breathing patterns affecting gas
exchange in the conducting airways; (ii) the concentrations in the
tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations
of the compound. The classical Farhi equation takes only the alveolar
concentrations into account. Real-time measurements of acetone in end-tidal
breath under an ergometer challenge show characteristics which cannot be
explained within the Farhi setting. Here we develop a compartment model that
reliably captures these profiles and is capable of relating breath to the
systemic concentrations of acetone. By comparison with experimental data it is
inferred that the major part of variability in breath acetone concentrations
(e.g., in response to moderate exercise or altered breathing patterns) can be
attributed to airway gas exchange, with minimal changes of the underlying blood
and tissue concentrations. Moreover, it is deduced that measured end-tidal
breath concentrations of acetone determined during resting conditions and free
breathing will be rather poor indicators for endogenous levels. Particularly,
the current formulation includes the classical Farhi and the Scheid series
inhomogeneity model as special limiting cases.Comment: 38 page