Subject-specific multi-scale modeling of the fate of inhaled aerosols

• Published in: Journal of aerosol science Vol. 183; p. 106471
• Main Authors: Kuprat, A.P., Feng, Y., Corley, R.A., Darquenne, C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2025; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Aerosol dosimetry; Computational fluid particle dynamics (CFPD); Host cell dynamics (HCD); Multi-scale modeling; Physiologically-based pharmacokinetics (PBPK); Subject-specific modeling; Aerosol dosimetry; Physiologically-based pharmacokinetics (PBPK); Host cell dynamics (HCD); Subject-specific modeling; Multi-scale modeling; Computational fluid particle dynamics (CFPD); multi-scale modeling; subject-specific modeling; host cell dynamics (HCD); computational fluid particle dynamics (CFPD); physiologically-based pharmacokinetics (PBPK); aerosol dosimetry
• ISSN: 0021-8502
• DOI: 10.1016/j.jaerosci.2024.106471

Determining the fate of inhaled aerosols in the respiratory system is essential in assessing the potential toxicity of inhaled airborne materials, responses to airborne pathogens, or in improving inhaled drug delivery. The availability of high-resolution clinical lung imaging and advances in the reconstruction of lung airways from CT images have led to the development of subject-specific in-silico 3D models of aerosol dosimetry, often referred to as computational fluid-particle-dynamics (CFPD) models. As CFPD models require extensive computing resources, they are typically confined to the upper and large airways. These models can be combined with lower-dimensional models to form multiscale models that predict the transport and deposition of inhaled aerosols in the entire respiratory tract. Understanding where aerosols deposit is only the first of potentially several key events necessary to predict an outcome, being a detrimental health effect or a therapeutic response. To that end, multiscale approaches that combine CFPD with physiologically-based pharmacokinetics (PBPK) models have been developed to evaluate the absorption, distribution, metabolism, and excretion (ADME) of toxic or medicinal chemicals in one or more compartments of the human body. CFPD models can also be combined with host cell dynamics (HCD) models to assess regional immune system responses. This paper reviews the state of the art of these different multiscale approaches and discusses the potential role of personalized or subject-specific modeling in respiratory health. •Hybrid 3D-1D lung models can predict aerosol deposition in the entire lung.•Subject-specific modeling improves predictions of inhaled aerosol deposition.•CFPD-PBPK models predict local and systemic exposure for inhaled medicines.•CPFD combined with host cell dynamics models immune response to inhaled particles.•AI/ML informed by computationally expensive 3D CFPD modeling speeds turnaround.