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Institutes for 1 Inhalation Biology and 3 Pathology, GSF-National Research Center for Environment and Health, D-85758 Neuherberg/Munich; and 2 Harvard School of Public Health, Department of Environmental Health, Boston, Massachusetts 02115
Long-term retention of particles in airways is controversial. However, precise anatomic localization of the particles is not possible in people. In this study the anatomic location of retained particles after shallow bolus inhalation was determined in anesthetized, ventilated beagle dogs. Fifty 30-cm3 boluses containing monodisperse 2.5-µm polystyrene particles (PSL) were delivered to a shallow lung depth of 81-129 cm3. At 96 h before euthanasia, red fluorescent PSL were used; at 24 h, green fluorescent PSL and 99mTc-labeled PSL were used. Clearance of 99mTc-PSL was measured during the next 24 h. Sites of particle retention were determined in systematic, volume-weighted random samples of microwave-fixed lung tissue. Precise particle localization and distribution was analyzed by using gamma counting, conventional fluorescence microscopy, and confocal microscopy. Within 24 h after shallow bolus inhalation, 50-95% of the deposited 99mTc-PSL were cleared, but the remaining fraction was cleared slowly in all dogs, similar to previous human results. The three-dimensional deposition patterns showed particles across the entire cross-sectional plane of the lungs at the level of the carina. In these locations, 33 ± 9.9% of the retained particles were found in small, nonrespiratory airways (0.3- to 1-mm diameter) and 49 ± 10% of the particles in alveoli; the remaining fraction was found in larger airways. After 96 h, a similar pattern was found. These findings suggest that long-term retention in airways is at the bronchiolar level.
aerosol bolus inhalation; convective gas transport; particle distribution in lungs; slow particle clearance from airways; fluorescent or radiolabeled polystyrene particles
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