(394a) Simulating Airflow in Human and Nonhuman Primate Airways with Applications to Aerosolized Drug Delivery Animal Testing

Assessing the human health benefits and risks from the inhalation of aerosolized medications is often performed by extrapolating experimental data taken using nonhuman primates animal studies to humans. Published results from these studies are often measurements of biological dose-response data that are corrected using coarse-grained allometric scaling to make predictions for humans. In this work we analyze how drug-delivery differs between species from a transport perspective. We use computational fluid dynamics alongside extensive in-vivo animal inhalation experiments to understand the dynamics of airflow in nonhuman primate lungs, and report on differences in aerosol transport and deposition mechanisms between humans and primates.

In the respiratory tract, inhaled aerosols must navigate the airways of the body and be deposited in targeted ways to maximize drug efficiency. Accurate analysis of drug efficacy and dosage requires an understanding of where these particles go upon inhalation. We report deposition fractions in airways across a range of particle sizes, breathing rates, and in numerous lung geometries. These computational results are validated with PET/CT experimental results. We compare these results with our previous report to show that differences in length scales between species produce fundamentally different time-dependent flow behavior and aerosol deposition mechanisms. Particle filtering in the nasal passages are reported for both species. In addition to patient-specific lungs, we compare and contrast the flow through statistically averaged bronchial trees of both humans and rhesus monkeys.

Additionally, we report on the success of novel simulation techniques that allow us to simulate deposition during a full inhalation/exhalation cycle. We employ advanced boundary conditions constructed using reduced-order modeling of the lower generations of the bifurcating airways and alveoli.