Purpose

The objective of this study was to optimize nose-to-lung aerosol delivery in an adult upper airway model using computational fluid dynamics (CFD) simulations in order to guide subsequent human subject aerosol delivery experiments.

Methods

A CFD model was developed that included a new high-flow nasal cannula (HFNC) and pharmaceutical aerosol delivery unit, nasal cannula interface, and adult upper airway geometry. Aerosol deposition predictions in the system were validated with existing and new experimental results. The validated CFD model was then used to explore aerosol delivery parameters related to synchronizing aerosol generation with inhalation and inhalation flow rate.

Results

The low volume of the new HFNC unit minimized aerosol transit time (0.2 s) and aerosol bolus spread (0.1 s) enabling effective synchronization of aerosol generation with inhalation. For aerosol delivery correctly synchronized with inhalation, a small particle excipient-enhanced growth delivery strategy reduced nasal cannula and nasal depositional losses each by an order of magnitude and enabled ~80% of the nebulized dose to reach the lungs. Surprisingly, nasal deposition was not sensitive to inhalation flow rate due to use of a nasal cannula interface with co-flow inhaled air and the small initial particle size.

Conclusions

The combination of correct aerosol synchronization and small particle size enabled high efficiency nose-to-lung aerosol delivery in adults, which was not sensitive to inhalation flow rate.

中文翻译：

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CFD 引导优化成人鼻对肺气雾剂输送：吸入波形和同步气雾剂输送的影响。

目的

本研究的目的是使用计算流体动力学 (CFD) 模拟优化成人上呼吸道模型中的鼻到肺气雾剂输送，以指导后续的人体气雾剂输送实验。

方法

开发了一个 CFD 模型，其中包括新的高流量鼻插管 (HFNC) 和药物气雾剂输送装置、鼻插管接口和成人上呼吸道几何形状。系统中的气溶胶沉积预测得到了现有和新实验结果的验证。然后使用经过验证的 CFD 模型来探索与同步气溶胶生成与吸入和吸入流速相关的气溶胶输送参数。

结果

新型 HFNC 装置的低容量最大限度地减少了气溶胶传输时间 (0.2 s) 和气溶胶丸剂扩散 (0.1 s)，从而实现气溶胶生成与吸入的有效同步。对于与吸入正确同步的气雾剂递送，小颗粒赋形剂增强的生长递送策略将鼻插管和鼻腔沉积物损失分别减少了一个数量级，并使约 80% 的雾化剂量能够到达肺部。令人惊讶的是，鼻腔沉积物对吸入流速不敏感，因为使用鼻插管接口与同流吸入空气和小初始粒径。

结论

正确的气溶胶同步和小粒径的结合使成人的鼻到肺气溶胶高效输送，对吸入流速不敏感。