An in silico inter-subject variability study of extra-thoracic morphology effects on inhaled particle transport and deposition
An in silico inter-subject variability study of extra-thoracic morphology effects on inhaled particle transport and deposition
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DOI：
10.1016/j.jaerosci.2018.05.010
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发表时间：
2018-09-01
影响因子：
4.5
通讯作者：
Lin, Jiang
中科院分区：
文献类型：
--
作者：
Feng, Yu;Zhao, Jianan;Lin, Jiang
了解人类受试者间的变异性对于实施个性化肺部药物输送以及空气中有害物质的暴露评估至关重要。然而，由于缺乏统计上可靠的数据和随后的比较，人类呼吸形态对吸入的纳米/微米颗粒输送和沉积的影响仍不完全清楚。因此，专注于识别显着影响气流和吸入颗粒输送/沉积的几何参数，开发了基于欧拉-拉格朗日方法的经过实验验证的计算流体颗粒动力学（CFPD）模型。在分析沉积模式以填补知识空白时，颗粒被分为六个直径组，即 0.05、0.1、0.5、2、5 和 10 μm。为了增强调查的统计稳健性，创建了一个虚拟群体，其中包含七种不同且广泛使用的人类上呼吸道配置，其中相同的气管支气管树延伸至第六代（G6）。数值结果和受试者间变异性分析表明，声门收缩是显着影响呼吸道吸入颗粒动力学的形态参数。出于统计稳健性的原因，应保持上呼吸道的解剖特征，以捕获小于 500 nm 或大于 2 μm 的颗粒的个性化气流和颗粒传输动力学。然而，代表基本亚群的单一上呼吸道模型可用于评估直径范围为 500 nm < d(p) < 2 μm 的颗粒的总沉积量。本研究提供了一个计算机肺气溶胶动力学框架，具有详细的颗粒沉积结果和新的物理见解。它可以作为实施吸入药物气溶胶最佳靶向以及评估不同人群中危险气溶胶暴露的指南。
An understanding of human inter-subject variability is crucial for the implementation of personalized pulmonary drug delivery as well as exposure assessment of airborne hazardous materials. However, due to the lack of statistically robust data and subsequent comparisons, the influence of human respiratory morphology on inhaled nano-/micro-particle transport and deposition is still not fully known. Thus, focusing on identifying geometric parameters that significantly influence airflow and inhaled particle transport/deposition, an experimentally validated Computational Fluid-Particle Dynamics (CFPD) model based on the Euler-Lagrange method is developed. In analyzing deposition patterns to fill the knowledge gap, the particles are grouped into six diameter groups, i.e., 0.05, 0.1, 0.5, 2, 5, and 10 mu m. To enhance the statistical robustness of the investigation, a virtual population group is created that contains seven distinct and widely used human upper-airway configurations, where the same tracheobronchial trees are extended to Generation 6 (G6). Numerical results and the inter-subject variability analysis indicate that the glottis constriction is the morphological parameter that significantly impacts the inhaled particle dynamics in the respiratory tract. For reasons of statistical robustness, anatomical features of the upper airways should be maintained to capture the personalized airflow and particle transport dynamics for particles smaller than 500 nm or larger than 2 mu m. However, a single upper airway model, representing a basic subpopulation group, can be employed to evaluate the total deposition of particles in the diameter range of 500 nm < d(p) < 2 mu m. The present study provides an in silico lung-aerosol dynamics framework with detailed particle-deposition results and new physical insight. It may serve as a guide for implementing optimal targeting of inhaled drug-aerosols as well as for the assessment of hazardous aerosol exposure in distinct populations.