Tutorial: Understanding the transport, deposition, and translocation of particles in human respiratory systems using Computational Fluid-Particle Dynamics and Physiologically Based Toxicokinetic models
Tutorial: Understanding the transport, deposition, and translocation of particles in human respiratory systems using Computational Fluid-Particle Dynamics and Physiologically Based Toxicokinetic models
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DOI：
10.1016/j.jaerosci.2020.105672
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发表时间：
2021-01-01
影响因子：
4.5
通讯作者：
Yi, Hang
中科院分区：
文献类型：
--
作者：
Feng, Yu;Zhao, Jianan;Yi, Hang
动态模拟颗粒物（PM）的运输，存款，并从人体呼吸系统的全身区域受到室内和室外暴露是必不可少的特定情况下的肺剂量预测和职业健康风险评估。由于现有的体外和体内方法的侵入性和成像分辨率的限制，计算流体-颗粒动力学加上基于生理学的药代动力学/毒代动力学（CFPD-PBPK/TK）模型已被用于预测可吸入气溶胶的命运几十年。本文介绍了如何使用多尺度CFPD-PBPK/TK模型来预测肺剂量和全身移位定量与三维主体特定的人体呼吸系统的指南。本教程旨在澄清可能存在歧义的概念。逐步建模程序应帮助研究人员准确地建立CFPD-PBPK/TK模型，遵循标准模型验证和验证（V&V）过程，并将肺剂量学预测带入健康终点。从CFPD和PBPK/TK控制方程的基本原理出发，本教程涵盖了问题识别，预处理，求解和后处理步骤，以执行计算肺气溶胶动力学模拟，强调（a）正确重建和肺气道网格生成的重要性;（B）选择合适的湍流模型来预测层流到湍流的肺气流状态的意义; CFPD-PBPK/TK建模框架中子模型的标准（V&V）过程。本教程还强调了当前CFPD-PBPK/TK模型的不足，澄清了呼吸系统中缺失的生物力学和气溶胶动力学，这些都需要考虑构建下一代虚拟人全肺模型。
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.