Tutorial: Understanding the transport, deposition, and translocation of particles in human respiratory systems using Computational Fluid-Particle Dynamics and Physiologically Based Toxicokinetic models

• Published in: Journal of aerosol science Vol. 151; p. 105672
• Main Authors: Feng, Yu, Zhao, Jianan, Hayati, Hamideh, Sperry, Ted, Yi, Hang
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.01.2021
• Subjects: Computational fluid-particle dynamics (CFPD); Physiologically based pharmacokinetic/toxicokinetic (PBPK/TK) model; The next-generation lung model; Virtual human; The next-generation lung model; Physiologically based pharmacokinetic/toxicokinetic (PBPK/TK) model; Virtual human; Computational fluid-particle dynamics (CFPD)
• ISSN: 0021-8502; 1879-1964
• DOI: 10.1016/j.jaerosci.2020.105672

Dynamic modeling of how particulate matter (PM) transport, deposit, and translocate from human respiratory systems to systemic regions subject to indoor and outdoor exposures are essential for case-specific lung dosimetry predictions and occupational health risk assessments. Because of the invasive nature and imaging resolution limitations of existing in vitro and in vivo methods, Computational Fluid-Particle Dynamics plus Physiologically Based Pharmacokinetic/Toxicokinetic (CFPD-PBPK/TK) models have been employed to predict the fate of the respirable aerosols for decades. This paper presents a guide on how to use the multiscale CFPD-PBPK/TK models to predict lung dosimetry and systemic translocations quantitatively with 3D subject-specific human respiratory systems. The tutorial aims to clarify possibly ambiguous concepts. The step-by-step modeling procedure should help researchers set up the CFPD-PBPK/TK model accurately, following the standard model validation and verification (V&V) processes, and to bring the lung dosimetry predictions to health endpoints. Starting from the fundamentals of CFPD and PBPK/TK governing equations, the tutorial covers the problem identification, pre-processing, solving, and post-processing steps to perform a computational lung aerosol dynamics simulations, emphasizing on (a) the importance of correct reconstruction and mesh generation of the pulmonary airways; (b) the significance of choosing the appropriate turbulence model to predict the laminar-to-turbulence pulmonary airflow regimes; and (c) the standard (V&V) procedures of submodels in the CFPD-PBPK/TK modeling framework. The tutorial also highlights the deficiencies of current CFPD-PBPK/TK models, clarifies the missing biomechanisms and aerosol dynamics in the respiratory systems that need to be considered to build the next-generation virtual human whole-lung models. •A step-by-step tutorial on how to establish the CFPD-PBPK/TK model is presented.•Key procedures to guarantee the accuracy of the CFPD-PBPK/TK simulations are emphasized.•Challenges and research directions to build the next-generation virtual lung model are discussed.