The research proposed is the first stage of a program focused on the development and critical evaluation of quantitative predictive models for gas and aerosol deposition efficiency in lung airways in humans and animals under a variety of respiratory modes and rates. The initial objective is to develop realistic physical models of the tracheobronchial airways of humans and experimental animals. The second objective is to use the models to examine the intrabronchial dose distribution of both gases and particles. Such measurements will provide basic experimental data on pollutant mass transfer. The complexity of flow profiles in both human and animal airways precludes useful predictions of mass transfer based on current fluid dynamics theory. The physical models to be made will permit examination of particle deposition in small bronchial and bronchioles for the first time. The ultimate objective is to develop predictive models for deposition using both theory and experimentally derived coefficients, including models that account for the pronounced nonuniformity of epithelial depositions on the airways. We propose to make single path hollow airway casts of human and dog tracheobronchial airways, including a cast composed of all major branches, a cast composed of minor branches, and a cast containing approximately equal numbers of major and minor branches. Flow distributions will be measured prior to cast pruning, and each branch removed will be replaced with an equivalent flow resistor. The casts will be fabricated so as to permit repeated assembly for experimental deposition measurements. Aerosol deposition in the small airways will be examined for the distinctly nonuniform deposition patterns that have been previously observed in the major human airways and, more recently, at alveolar duct bifurcations in rodents. The utility of the casts for quantitative detailed gas dosimetry will be demonstrated using NO as a model air pollutant and triethanolamine (TEA) as an absorbing surface. Overall deposition efficiencies at each airway segment and the pattern of deposition within airways will be defined for various constant and cyclic flow rates. Comparative measurements in these realistic flow systems with the NO2-TEA system and with nondiffusing, noninertial particles will provide basic flow profile information needed for predictive dose estimation.
