Inhalation exposure and particle deposition across 16 nonhuman primate airway models using computational...

Nonhuman primates are indispensable surrogate models for humans due to their evolutionary proximity; however, ethical concerns and practical constraints are increasingly limiting their use. Computational fluid-particle dynamics (CFPD) offers a promising alternative for inhalation exposure studies; however, previous studies typically used small sample sizes with limited model validation. Therefore, this study aims to elucidate inhalation exposure in monkeys through a large cohort analysis and to identify relationships between humans and monkeys by allometric comparison.

In this study, we reconstruct anatomically accurate upper airway models from computed tomography (CT) data of 16 macaques (Macaca fuscata and Macaca mulatta). Steady-state airflow and particle transport simulations are performed using high-resolution meshes with verified grid independence. Particle aspiration and deposition efficiencies are evaluated across 11 microparticles using the Lagrangian particle tracking.

Airway geometry was found to strongly influence the airflow resistance, velocity distribution, and wall shear stress. These factors resulted in substantial interindividual variability in aspiration and particle deposition patterns. Comparative analysis with pediatric human models revealed morphological correspondences. The mean nasal cross-sectional area correlated more strongly with age than the minimal nasal cross-sectional area or region-specific areas. Normalizing deposition efficiency by a modified Stokes number substantially reduced intersubject variability and yielded a high-fidelity logistic fit.

These findings emphasize the importance of incorporating both age- and morphology-dependent factors into interspecies extrapolations. Therefore, this study provides a basis for more reliable assessments of inhalation exposure and enhances the validity of extrapolating data from monkeys to humans.