Supplementary Data: On the mechanics of inhaled bronchial transmission of pathogenic microdroplets generated from the upper respiratory tract, with implications for downwind infection onset

Could the microdroplets formed by viscoelastic fragmentation of mucosal liquids within the upper respiratory tract (URT) explain the brisk onset of deep lung infection following initial URT infections? Generally, particulates, inhaled through the nostrils and therefore navigating the intricate topography of the anterior nasal cavity, can efficiently reach the lower airway only if they are small enough, typically &lt; 5 microns. However, the fate of larger particulates, many exceeding 5-micron in diameter, that are sheared from the initial infection sites along the intra-URT mucosa during inhalation remains unresolved. These particulates originate primarily from the nasopharynx, oropharynx, and the laryngeal chamber containing the vocal folds. To investigate, this study employs a computed tomography-based three-dimensional anatomical airway reconstruction, isolating the tract from the larynx and mapping the tracheal cavity through to the third generation of the tracheobronchial tree; constituent transport across the distal bronchial outlets is also recorded to assess deep lung penetration. Within the defined geometry, airflow simulations are conducted with the Large Eddy Simulation scheme to replicate relaxed inhalation at 15 L/min flow rate. Against the ambient air flux, numerical experiments are performed to monitor the transport of particulates (aerosols/droplets) with diameters 1-30 microns, bearing physical properties akin to aerosolized mucus with embedded virions. The full-scale numerical transmission trends, representatively validated against a small set of published experimental data, are consistent with findings from our reduced-order mathematical model that conceptualizes the influence of intra-airway vortex instabilities on local particle transport through point vortex idealization in an anatomy-guided two-dimensional potential flow domain. The results collectively demonstrate a markedly elevated lower airway penetration by URT-derived particulates, even by those as large as 10 and 15 microns. The high viral load, often exceeding the pathogen-specific infectious dose, carried by such droplets into the bronchial spaces of the sample airway, provides a plausible mechanistic explanation for the accelerated seeding of secondary lung infection.Uploaded by: Dr. Saikat Basu (Contact: [e-mail])<br>Dated: August 28, 2025

上呼吸道（upper respiratory tract，URT）黏膜液体经粘弹性碎裂形成的微滴，能否解释初始上呼吸道感染后肺部深部感染的快速发作？通常而言，经鼻腔吸入的颗粒物需穿过前鼻腔复杂的解剖结构，仅当粒径足够小时（通常小于5微米）才能有效抵达下呼吸道。然而，吸气过程中沿上呼吸道黏膜从初始感染部位剪切产生的更大粒径颗粒物（许多直径超过5微米）的最终去向仍未明确。此类颗粒物主要源自鼻咽部、口咽部以及包含声带的喉腔。为探究该问题，本研究采用基于计算机断层扫描（computed tomography，CT）的三维气道解剖重建方法，从喉部分离气道并绘制气管腔直至气管支气管树第三代分支的通路；同时记录颗粒物通过远端支气管开口的输运情况，以评估其肺部深部穿透能力。在确定的几何模型中，本研究采用大涡模拟（Large Eddy Simulation，LES）方案开展气流模拟，以复现15升/分钟流速下的平静吸气状态。针对环境气流，本研究开展数值实验，监测直径1~30微米、具有与载有病毒粒子的雾化黏液相似物理特性的颗粒物（气溶胶/液滴）的输运过程。针对少量已发表实验数据进行代表性验证后的全尺寸数值输运趋势，与我们的降阶数学模型结果一致；该模型通过在解剖学引导的二维势流域中采用点涡理想化方法，刻画了气道内涡旋不稳定性对局部颗粒物输运的影响。研究结果整体表明，源自上呼吸道的颗粒物（即便粒径达10和15微米），其下呼吸道穿透率显著提升。此类液滴携带的病毒载量通常超过病原体特异性感染剂量，并被输送至样本气道的支气管区域，这为继发性肺部感染的快速定植提供了合理的机理解释。<br>上传者：赛卡特·巴苏博士（联系方式：[e-mail]）<br>日期：2025年8月28日