Basic physical concepts of diffusion, convection, and dispersion pertaining to gas transport in the human airways are reviewed. Their incorporation into quantitative models of gas mixing is presented, also illustrating the crucial interaction of gas transport equations with the model geometry. Model simulations are confronted with the available experimental gas mixing indices such as the phase III slope obtained in normal human lungs, with some pertinent examples in laboratory animals and in human lung disease. The use of inert gases with differing diffusion coefficients and their associated phase III slope provides invaluable experimental information on gas mixing in the lungs, with the concept of the diffusion front playing a central role. Sources of inter- and intraregional ventilation heterogeneity can be related to the location of the diffusion front, which offers the possibility to distinguish between ventilation heterogeneity proximal to the diffusion front (driven by convection between lung units larger than acini) and more peripheral ventilation heterogeneity (driven by diffusion-convection interaction mainly within the acinus). While specific ventilation distribution and flow asynchrony co-act to generate convection-dependent ventilation heterogeneity, local structural asymmetry of the acinar air spaces is sufficient to generate diffusion-convection-dependent ventilation heterogeneity. The remaining hiatus in our understanding of ventilation heterogeneity in the human lung is described, together with some potential perspectives for its investigation.
© 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.