呼吸道内通过吸入气溶胶传播天花的机制模型
A mechanistic model for smallpox transmission via inhaled aerosols inside respiratory pathways
AI总结：
本研究构建多尺度模型，结合大涡模拟与天花病毒学、流行病学参数，揭示呼吸道内流体动力学对吸入含病毒气溶胶的感染引导作用，推算的天花感染剂量与已知参数高度吻合。
摘要：
病原体空气传播研究是一个快速发展的领域，主要聚焦于理解受感染宿主呼吸道颗粒物的排出模式及其在密闭空间中的扩散情况。流体动力学在引导吸入的含病毒颗粒物进入呼吸道腔、进而将病原体导向易感染的上呼吸道部位方面的关键作用，在很大程度上被忽视了。本文提出了一种基于流动物理学模拟气道感染起始参数的多尺度方法。研究结果得到了吸入气流大涡模拟（Large Eddy Simulations）的支持，我们对两个经计算机断层扫描成像重建的、临床健康且解剖结构真实的气道模型内的携带病原体的气溶胶/液滴轨迹进行了计算。作为一种可通过空气传播的典型各向异性病原体，我们选取了痘病毒科（Poxviridae）的天花来验证该方法。我们将吸入传播趋势的流体动力学研究结果与天花的病毒学和流行病学参数（例如宿主排出物中的病毒浓度、病毒粒子的物理特性以及典型暴露时长）相结合，确定了相应的感染剂量（即足以引发暴露个体感染的病毒粒子数量）最多为O(2)量级，更精确地说为1至180个。该预测结果与已知的天花病毒学参数高度吻合。
英文摘要：
Investigations on airborne transmission of pathogens constitute a rapidly expanding field, primarily focused on understanding the expulsion patterns of respiratory particulates from infected hosts and their dispersion in confined spaces. Largely overlooked has been the crucial role of fluid dynamics in guiding inhaled virus-laden particulates within the respiratory cavity, thereby directing the pathogens to the infection-prone upper airway sites. Here, we discuss a multi-scale approach for modeling the onset parameters of airway infection based on flow physics. The findings are backed by Large Eddy Simulations of inhaled airflow and computed trajectories of pathogen-bearing aerosols/droplets within two clinically healthy and anatomically realistic airway geometries reconstructed from computed tomography imaging. As a representative anisotropic pathogen that can transmit aerially, we have picked smallpox from the Poxviridae family to demonstrate the approach. The fluid dynamics findings on inhaled transmission trends are integrated with virological and epidemiological parameters for smallpox (e.g., viral concentration in host ejecta, physical properties of virions, and typical exposure durations) to establish the corresponding infectious dose (i.e., the number of virions potent enough to launch infection in an exposed subject) to be, at maximum, of the order of O(2), or more precisely 1 to 180. The projection agrees remarkably well with the known virological parameters for smallpox.
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