Comparative simulation of gas transport in airway models of rat, dog, and human

Although a number of animal studies have been conducted to investigate the toxic effects of gaseous pollutants on human airways, the anatomical and physiological differences between animals and humans represent a challenge in extrapolating the animal data to humans. The aim of this study was to examine how interspecies anatomical and physiological differences influence the transport of the inhaled gases throughout the airways and alveoli. We designed mathematical airway models of three mammalian species, rats, dogs, and humans, in which interspecies differences in airway dimensions and respiratory patterns were taken into account. We then simulated the bulk flow of three gases (ozone [O-3], nitrogen dioxide [NO2], and sulfur dioxide [SO2]) and obtained the intra-airway concentrations of the gases and the amount absorbed using these models. For all three gases, both real-time and mean concentrations in the upper and lower airways were higher in humans when compared with rats and dogs. For example, the mean concentration of O-3 in the 5th bronchi of humans was 3 and 12 times higher than in rats and dogs, respectively. Similarly, the amount of absorbed gases corrected for airway surface area was again higher in the upper and lower airways of humans than the other two species. Sensitivity analysis indicated that tidal volume, respiratory rate, and surface area of the upper and lower airways had significant impact on the results. In conclusion, kinetics of inhaled gaseous substances vary substantially among animals and humans, and such variations are, at least partially, the result of anatomical and physiological differences in their airways.