Transient Absorption of Inhaled Vapors into a Multilayer Mucus–Tissue–Blood System

Abstract

Previous studies have approximated the absorption of vapors into the walls of the respiratory tract as a steady state process. However, non-dimensional analysis indicates that the absorption of vapors in the conducting airways is time-dependent over the timescale of a breathing cycle. The objective of this study was to evaluate the mass transport of sample chemical species through a simple multilayer system composed of mucus, tissue, and blood components on a transient basis. Individual multilayer models were considered that represent the wall dimensions of the nasal extrathoracic (ET(2)), bronchial (BB), and bronchiolar (bb) airways. Sample vapors considered were acetaldehyde and benzene, which are highly soluble and moderately soluble in mucus, respectively. To determine absorption, mass transport was calculated based on an existing analytical steady state solution, a new analytical transient solution, and a numerical transient solution. Results indicated that concentrations within the mucus and tissue layers were highly time dependent in the ET(2) and BB regions and moderately time dependent in the bb airways over the timescale of an inhalation cycle, which is approximately 1-2 s. Fluxes of vapors into the tissue and blood varied with time for approximately 6-8 s in the BB region and 0.6-0.8 s in the bb model. The associated transient blood uptake of acetaldehyde and benzene in the upper ET(2) and BB regions varied from steady state values by a factor of approximately 30 after 1 s. Under similar conditions, transient uptake in the bb model varied from steady state conditions by a factor of approximately 1.3. Surprisingly, inclusion of chemical reactions in the mucus and tissue modified the transient uptake predictions only for very large values of reaction rate coefficients (K > 100 min(-1)). In summary, transient effects significantly impact the absorption of vapors into the walls of the upper respiratory tract (ET(2) and BB regions) and may largely diminish the effects of chemical reactions over the timescale of an inhalation cycle. Furthermore, the transient analytical solution that was developed provides the basis for an improved boundary condition in future CFD simulations of air-phase transport and wall absorption.

Application of a new dosimetry program TAOCS to assess transient vapour absorption in the upper airways

“…However, 1-D models and experiments clearly show that blood concentrations increase over longer timescales (Kumagai and Matsunaga, 1995). An analytical solution of this system was previously developed by Tian and Longest (2010a) and extended to formulate a CFD boundary condition including the air phase by Tian and Longest (2010b). The analytical solution for the concentration of an absorbed species in the mucus and tissue layers is briefly reviewed below.…”

“…The validity of this assumption has recently been questioned by Longest et al Specifically, Tian and Longest (2010a) showed that transient wall absorption significantly influences uptake over the timescale of one inhalation cycle in the upper airways. For example, Tian and Longest (2010a) found that the uptake of highly and moderately soluble compounds modelled with transient fluxes varied from steady state flux estimates by a factor of ∼30 in nasal and upper TB models after 1 s. As a result, it appears important to consider a time-dependent (or transient) flux value when estimating absorption into the respiratory airway walls. This is especially true in the early stages of exposure where blood concentration values of the inhaled species are near zero.…”

“…This is especially true in the early stages of exposure where blood concentration values of the inhaled species are near zero. The results of Tian and Longest (2010a) were based analytical and numerical solutions of transient absorption into a simple mucus-tissue-blood wall representation. However, a constant vapour concentration was assumed at the air-mucus interface and the air phase transport was neglected.…”

Derivation of Mass Transfer Coefficients for Transient Uptake and Tissue Disposition of Soluble and Reactive Vapors in Lung Airways

“…25,36 In these studies, the transport of vapor in the tissue has been considered steady state, leading to one-way vapor transport from the air to tissue phases. However, Tian and Longest 41 showed that based on the calculated mass transfer Fourier number, this process is unsteady. Recently, Tian and Longest [39][40][41] published a series of articles on the transient absorption of vapors in respiratory airways using an uptake model that included a mucus-tissue-blood layer.…”

“…However, Tian and Longest 41 showed that based on the calculated mass transfer Fourier number, this process is unsteady. Recently, Tian and Longest [39][40][41] published a series of articles on the transient absorption of vapors in respiratory airways using an uptake model that included a mucus-tissue-blood layer. They developed a wall-flux boundary condition for transient absorption that was applied to CFD models of vapor uptake in the respiratory tract.…”