The proposed research aims at investigating the inhomogeneity of gas mixing and ventilation distribution in the lungs of normal subjects and patients with various types of airflow obstruction. The research will focus on the distinction between the interaction of convection and diffusion, producing a diffusion-dependent inhomogeneity within the lung periphery, and ventilation maldistribution among larger units subtended by more proximal branchponts. We propose to explore a newly developed method giving an index of ventilation maldistribution that is very sensitive to the connection-dependent component. The method, which allows a functional localisation of ventilation maldistribution will be used to explore various physiological factors such as the effect of frequency and bronchomotor tone on gas distribution in normal subjects. Studies in patients will be aimed at determining the differences in both magnitude and nature of the inhomogeneity inferred by the method of analysis. We plan to study gas transport through the conducting airways of normal subjects by analysing the phase II of single breath washouts in terms of a distribution function. By using gases of different diffusivity we shall attempt to define the contribution of the diffusion-dependent and diffusion (or time) independent component to the dispersion of gases reflected in the phase II of the washout. Finally we intend to extend our theoretical studies with a multibranchpoint model incorporating acinar asymmetry to include the aspects of ventilation maldistribution e.g. inequality of regional ventilation, inequality of dead spaces, and convective sequencing both a regional and an intraregional level. By relating simulations to experimental findings in the present and other studies, we hope to gain insight into the specific pattern of gas mixing and ventilation distribution in the lung.
