Route of Pulmonary Administration of Aerosols and the Size of Aerosols Significantly Affects Particle Deposition and Cellular Recruitment

RYAN W. DROVER, Keziyah Yisrael, Malia L. Shapiro, Martha Anguiano, Nala Kachour, Qi Li, Emily Tran, David R. Cocker III, David D. Lo, University of California, Riverside

     Abstract Number: 28
     Working Group: Health-Related Aerosols

Abstract
Lung exposures to dusts, pollutants, and other aerosol particulates are known to be associated with a number of pulmonary diseases, including asthma and Chronic Obstructive Pulmonary Diseases. These health impacts are related to the ability of aerosol components to induce lung tissue inflammation, which promotes tissue remodeling, including fibrosis, tissue degradation, and smooth muscle proliferation, so the distribution of these effects can have a significant impact on lung physiologic function. To study the impact of distribution of inhaled particulates on lung pathogenesis, we compared the effect of different modes of aerosol delivery. Intranasal versus aerosol delivery of fluorescent microspheres showed strikingly different patterns of particle deposition; intranasal delivery provided focused deposition concentrated on larger airways, while aerosol delivery showed uniform deposition throughout the lung parenchyma. Since inflammatory cell impacts will also depend on the recruitment and behavior of the recruited cells, we then studied the responses to administration of endotoxin (bacterial Lipopolysaccharide, or LPS). Similar to the microsphere results, patterns of recruited neutrophil inflammatory responses matched the delivery method; that is, despite the migratory potential of active neutrophils, inflammatory histopathology patterns were either focused on large airways (intranasal administration) or diffusely throughout the parenchyma (aerosol). These results help establish validated models to study the impacts of aerosol exposures, as different patterns of inflammation and tissue remodeling will have distinct impacts on aspects of lung physiology.