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

Area of Science:

• Inhalation toxicology and biophysics
• Comparative anatomy and physiology
• Computational modeling and simulation

Background:

• Nonhuman primates are valuable human surrogates, but their use is restricted by ethical and practical issues.
• Computational fluid-particle dynamics (CFPD) offers an alternative for inhalation studies but requires robust validation.
• Previous CFPD studies often used small sample sizes, limiting the generalizability of findings.

Purpose of the Study:

• To analyze inhalation exposure in a large cohort of macaques using CFPD.
• To establish relationships between human and monkey inhalation exposure through allometric comparison.
• To enhance the reliability of using primate models for human inhalation exposure assessments.

Main Methods:

• Reconstruction of 16 macaque upper airway models from CT data.
• Steady-state airflow and particle transport simulations using high-resolution, grid-independent meshes.
• Evaluation of particle aspiration and deposition efficiencies for 11 microparticle sizes via Lagrangian particle tracking.

Main Results:

• Airway geometry significantly impacts airflow resistance, velocity, and wall shear stress, causing interindividual variability in particle deposition.
• Morphological similarities were observed between macaque and pediatric human airway models.
• Normalizing deposition efficiency by a modified Stokes number reduced variability and improved predictive modeling.

Conclusions:

• Age and morphology are critical factors for accurate interspecies extrapolation of inhalation data.
• CFPD analysis in macaques provides a foundation for more reliable inhalation exposure assessments.
• This study validates and enhances the extrapolation of inhalation data from monkeys to humans.