Human tracheobronchial deposition and effect of a cholinergic aerosol inhaled by extremely slow inhalations

Ten subjects inhaled the same amounts of cholinergic aerosol of a mass medi an diameter (MMD) of 7.7 mu m in a normal provocation test and In a test wi th extremely slow inhalations (ESI). This new technique using ESI and large droplets/particles gives a high degree of deposition in small ciliated air ways which cannot be obtained by using small particles. The purpose was to compare measured effects with calculated doses of the aerosol in large end small ciliated airways. The effect on large airways was measured by airway resistance (R-aw), and the effect on small airways was measured by the phas e III slope of single breath nitrogen test (N-2-delta). Mouth and throat de position was calculated from human experimental data, and deposition of the cholinergic aerosol into large and small airways was calculated, using a c omputerized lung model. The study showed that the extremely slow inhalation caused a larger effect on R-aw and tendency to a larger effect on N-2-delt a compared to the effect in the normal provocation. Deposited dose in the l arge airways, in percent of inhaled dose, was calculated to be 25-33% for n ormal inhalation and 20-24% for ESI. Calculated deposited dose ill the smal l airways (bronchioles; generations 12-16) was 1.8-3.4% for normal inhalati on and 18-25% for ESI. For large airways a stronger effect was induced by E SI, perhaps by the more uniform distribution of particles within each gener ation, compared to normal inhalations when particles deposit near the bifur cations. Concerning the small airways, N-2-delta did not differ significant ly between normal and ESI provocations, indicating that they did not react much an cholinergic exposure. We believe that our approach using ESI for sm all airway deposition of a nebulized aerosol can be of value for estimating the effects of various substances on large and small airways.