CHRONIC-BRONCHITIS ALTERS THE PATTERN OF AEROSOL DEPOSITION IN THE LUNG

Knowledge of the local and regional doses of inhaled particulates is crucial for inhalation therapy and for understanding the progression of pulmonary disease. We studied the deposition pattern of radioactively tagged particles in rats with chronic bronchitis. Rats were exposed to sulfur dioxide (SO2; 236 +/- 14 ppm) for 5 h/d, 5 d/wk for 7 wk to produce chronic bronchitis (CB). Control rats were exposed to room air. The control animals gained 85% more weight over the 7-wk period than did the CB rats. Five control and five CB rats were then exposed for 30 min to an insoluble Tc-99m-labeled aerosol. The animals were killed within 5 min after the exposure period. The lungs were excised, dried at total lung capacity (TLC), and sliced into 1 mm sections. The distribution of the radiolabeled particles retained in the lungs was determined in two ways. First, autoradiographs were made of the distribution of the radioactivity throughout a lung slice. Autoradiographs were quantified by image analysis to determine the amount of radioactivity (relative density of the film) associated with airway versus parenchyma (ratio of airway to parenchyma density). The lung slices were then dissected into pieces, the weight and radioactivity content of each piece was measured, and its evenness index (El) was calculated. Th is type of analysis enables the homogeneity of particle deposition throughout the lungs to be assessed. If deposition were totally uniform, the average Fl would be 1.0 with an SD = 0. The total amount of radioactivity retained in the lungs was similar in control and CB rats. Yet particles were nonhomogeneously distributed throughout the chronic bronchitic rat lungs compared with those of control animals. The SD of all Els was 0.27 for controls but 0.49 for bronchitic rats. A greater percentage of pieces from the CB rat lungs (8.0 +/- 3.1%) retained few or no particles (El < 0.2). Less than 0.6% of the pieces from control lungs had Els less than or equal to 0.2. Autoradiographs revealed increased deposition associated with airways in CB lungs as compared with control lungs. The ratio of the average grey level in airways/parenchyma increased by 113% in the CB rats. This rat model of SO2-induced chronic bronchitis produces airway changes similar to the human disease, and upon aerosol exposure, exhibits heterogeneous patterns with enhanced airway deposition.