Particle and inhalation exposure in human and monkey computational airway models

Regional deposition of inhaled aerosols is essential for assessing health risks from toxic exposure. Upper airway physiology plays a significant role in respiratory defense by filtering micrometer particles, whose deposition mechanism is predominantly inertial impaction and is mainly controlled by airflow characteristics. The monkey is commonly used in tests that study inhalation toxicity as well as in pre-clinical tests as human surrogates due to their anatomical similarities to humans. Therefore, accurate predictions and an understanding of the inhaled particles and their distribution in monkeys are essential for extrapolating laboratory animal data to humans. The study goals were as follows: (1) to predict the particle deposition based on aerodynamic diameters (1-10 mm) and various steady inspiratory flow rates in computational models of monkey and human upper airways; and (2) to investigate potential differences in inhalation flow and particle deposition between humans and monkeys by comparing numerical simulation results with similar in-vitro and in-vivo measurements from recent literature. The deposition fractions of the monkey's numerical airway model agreed well with in-vitro and human model data when equivalent Stokes numbers were compared, based on the minimum cross-sectional area as representative of length scale. Vestibule removal efficiencies were predicted to be higher in the monkey model compared with the human model. Our results revealed that the particle transportations were sensitive to the anatomical structure, airway geometry, airflow rates, inflow boundary conditions and particle size.

吸入气溶胶在区域内的沉积对于评估有毒物质暴露带来的健康风险至关重要。上呼吸道生理机能在呼吸防御中起着重要作用，它能过滤微米级颗粒，其沉积机制主要是惯性撞击，且主要受气流特性控制。由于猴子在解剖结构上与人类相似，所以在吸入毒性研究以及临床前试验中常被用作人类的替代物。因此，准确预测和了解吸入颗粒及其在猴子体内的分布情况，对于将实验动物数据外推至人类至关重要。研究目标如下：（1）在猴子和人类上呼吸道的计算模型中，根据空气动力学直径（1 - 10毫米）以及各种稳定的吸气流量来预测颗粒沉积；（2）通过将数值模拟结果与近期文献中类似的体外和体内测量结果进行比较，研究人类和猴子在吸气流量和颗粒沉积方面的潜在差异。当以最小横截面积作为长度尺度的代表来比较等效斯托克斯数时，猴子数值气道模型的沉积分数与体外和人类模型数据吻合良好。据预测，与人类模型相比，猴子模型的前庭清除效率更高。我们的研究结果表明，颗粒传输对解剖结构、气道几何形状、气流速率、流入边界条件和颗粒大小较为敏感。