Simulation of the regional manifestation of asthma.

Asthma presents serious medical problems of global proportions. Clinical data suggest that the disease occurs preferentially at regions designated by large (0 </= I </= 5), central (6 </= I </= 11), and small (12 </= I </= 16) airways, where I defines branching generations within lungs. Our straightforward hypothesis, therefore, was that the efficacies of pharmacologic drugs proposed for the treatment and prophylaxis of asthma would be enhanced via their targeted delivery to appropriate sites. Hence, we have developed a mathematical model describing the behavior and fate of inhaled aerosols. Original algorithms have been derived to detail the physical manifestation of asthma as distinct components of smooth muscle constriction and inflammation. We have conducted a systematic analysis of the relative effects of morphology, ventilation, and particle size on aerosol deposition. Different intensities of asthma were simulated by reducing airway diameters by prescribed amounts. To show the real clinical applications of modeling, we have also simulated the performance of a popular nebulizer. Regarding therapeutic implications, it is clear that disease-induced changes in airway morphologies have pronounced effects on the administration of inhaled drugs. Likewise, ventilation affects both the total aerosol mass deposited and its relative spatial distribution among airways. By formulating these effects, the computer code allows drugs (e.g., bronchodilators for constriction, steroids for inflammation) to be selectively deposited. We suggest, therefore, that the code can be used in a complementary manner with clinical studies and can be integrated into aerosol therapy regimens. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1205-1216, 2004