Subject-Specific Multi-Scale Modeling of the Fate of Inhaled Aerosols

Area of Science:

• Respiratory system modeling
• Inhaled aerosol dynamics
• Computational toxicology

Background:

• Accurate prediction of inhaled aerosol fate is crucial for assessing toxicity, pathogen response, and drug delivery efficacy.
• High-resolution lung imaging and airway reconstruction enable subject-specific 3D computational fluid-particle-dynamics (CFPD) models.
• CFPD models, computationally intensive, are often limited to upper airways, necessitating multiscale approaches.

Purpose of the Study:

• To review state-of-the-art multiscale modeling approaches for inhaled aerosols in the respiratory tract.
• To discuss the integration of computational fluid-particle-dynamics (CFPD) with other models for comprehensive respiratory analysis.
• To explore the role of personalized, subject-specific modeling in advancing respiratory health.

Main Methods:

• Combining computational fluid-particle-dynamics (CFPD) with lower-dimensional models for whole-tract aerosol transport and deposition.
• Integrating CFPD with physiologically-based pharmacokinetics (PBPK) models to evaluate ADME (absorption, distribution, metabolism, excretion).
• Coupling CFPD with host cell dynamics (HCD) models to assess regional immune responses.

Main Results:

• Multiscale models enable prediction of aerosol transport and deposition throughout the entire respiratory tract.
• Integrated models facilitate evaluation of chemical ADME and regional immune responses.
• Subject-specific modeling holds significant potential for personalized respiratory health applications.

Conclusions:

• Multiscale modeling approaches offer a powerful framework for understanding inhaled aerosol behavior.
• Integration of CFPD with PBPK and HCD models enhances the assessment of health effects and therapeutic outcomes.
• Personalized modeling is key to advancing individualized strategies in respiratory medicine and toxicology.