Enhanced Aerosol Deposition in the Lung with Mild Airways Obstruction

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Abstract
We investigated the sensitivity of aerosol deposition to airways obstruction by measuring total deposition fraction of inert aerosol in normal conscious sheep (n = 6) after challenging cholinergic agent, pilocarpine (PL) (0.5 mg/kg intravenously) with and without a prior challenge of .beta.2-adrenergic agonist, terbutaline sulfate (TS) (0.025 mg/kg subcutaneously). Aerosol deposition was measured by a light-scattering aerosol photometer in situ while sheep rebreathed 1.0-.mu.m-diamether inert oil droplets from a 0.2-L collapsible bag at a rate of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as a percentage of initial aerosol concentration was determined and compared with mean pulmonary airflow resistance (RL). After PL, both AD5 and RL increased significantly from baseline values by 51 .+-. 9% and 597 .+-. 118% (mean .+-. SE), respectively, whereas AD5 and RL decreased significantly by 16 .+-. 4% and 34 .+-. 6%, respectively after TS (p < 0.05). After PL subsequent to TS (TS-PL), AD5 increased in all six sheep by 33 .+-. 7% from post-TS values (p < 0.05). However, RL did not change from post-TS values. Greater changes in RL than in AD5 after PL (bronchoconstriction) or TS (bronchodilation) suggest a greater sensitivity of RL than AD5 to airway patency in the large airways. Lack of increase of RL after TS-PL indicated that bronchoconstrictive effect of PL was blocked by prior challenge with TS. Therefore, the increase in AD5 after TS-PL may be related to the peripheral airway obstructions which might have been caused by increased secretions induced by a potent secretagogue PL. The results suggest that total aerosol depositon fraction in the lung increases with obstructions in the airways and is particularly sensitive to mild airways obstructions undetectable by RL.