Experimental studies will be performed to determine the range of sizes of the bronchial and alveolar airspaces in human lungs and the effects of variations in airspace dimensions on the regional deposition of inhaled particles. Measurements of in vivo particle deposition will be made, for both cigarette smokers and nonsmokers, with monodisperse aerosols of triphenyl phosphate and ferric oxide, the latter being tagged with 99mTc or 198Au. Concurrently, a series of sequential measurements will be made on the freshly excised lungs of adult smokers, nonsmokers, and children dying accidentally, and on hollow airway casts and tissue sections made from these lungs. Measurements will include: respiratory mechanical function, airspace sizes using aerosol probes, bronchial airway morphometry on solid lung casts, intrabronchial deposition patterns in hollow airway casts, and alveolar airspace dimension on lung sections. In addition, similar techniques will be applied in tests performed on donkeys, involving in vivo aerosol deposition, sacrifice, tests of mechanical function and aerosol deposition in their excised lungs, preparation of lung casts and tissue sections, and measurements of particle deposition and airspace sizes in them. Direct comparisons will be between in vivo airspace sizes and those measured in the casts and sections, and between airspace sizes and particle deposition. The results of all of these tests will be incorporated into predictive deposition models which take anatomic variability into account, including variability associated with age, cigarette smoking, and constitutional factors.
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