Modeling aerosol deposition in human airways

The very design that makes the lung an efficient gas exchanger also makes it vulnerable to insult by inorganic and organic aerosols. Epidemiological studies have shown a positive association between ambient aerosol exposure and health risks. Understanding particle dosimetry in the lung is the first step toward explaining particulate induced pulmonary dysfunction. In addition to understanding the deleterious effect of ambient particles, such studies are also helpful in engineering the delivery of therapeutic aerosols to the lung. Various animals are employed in experimental aerosol inhalation toxicology studies to determine particle lung dosimetry. To adequately apply the animal results to human risk assessment we need mathematical models that incorporate mechanistic determinants of disposition to extrapolate the exposure-dose data derived from experimental animals to humans.; The specific aim of this thesis is to develop a particle deposition model for the whole lung using fundamental principles of fluid mechanics and aerosol science. To accomplish this the lung has been divided into two broad regions: (1) the upper airways and (2) the lower airways. Due to the complex geometry of the upper airways, a computational fluid dynamics approach is used to address the issue of particle deposition in this region. For the lower airways, which have a regular bifurcating geometry, a simple compartmental model is used to study particle dosimetry. Aerosol dispersion in the human airways has a significant influence on the regional particle dosimetry. A model for dispersion using simple fluid mechanical principles is proposed and this model is incorporated into the deposition model to show why properly accounting for dispersion is critical to accurately assess the human health risk due to inhaled particulate matter.