Development of Idealized Geometries that Mimic Upper Airway Deposition of Aerosols and Sprays

我们呼吸的空气中的颗粒物是有害健康的主要来源。另一方面，将空气传播的颗粒有意识地输送到呼吸道是输送用于治疗疾病（例如哮喘、流感和鼻炎等）的治疗药物的重要方法。出于这些原因，了解和预测呼吸道中颗粒的行为对于评估与环境气溶胶暴露相关的风险以及改善依赖于药物输送到呼吸道的治疗都很重要。 由于吸入的颗粒必须通过鼻子或嘴巴进入呼吸道（所谓的上呼吸道），因此了解这些颗粒的命运始于了解它们在上呼吸道中的命运。在二十多年的时间里，阿尔伯塔的气溶胶研究实验室（ARLA）系统地探索了上呼吸道中的颗粒行为，导致我们开发了理想化的上呼吸道物理模型，该模型现在被加拿大和世界各地的许多学术研究人员和40多家公司用于气溶胶暴露研究以及吸入器的开发和测试。 尽管取得了这一成功，但我们在体外评估上气道沉积的能力方面存在几个主要差距。这些差距之一包括缺乏模拟纳米颗粒沉积的理想化上气道模型。第二个差距是缺乏模拟学龄前儿童口腔沉积微米直径颗粒的理想模型。最后的差距是缺乏理想化的鼻气道来模拟鼻腔给药喷雾剂的沉积。我们建议填补这些空白，首先进行广泛的实验和模拟的行为的气溶胶和喷雾剂的复制品的上呼吸道的人类受试者。使用从出生到成年的几个年龄范围中的每一个大约十几个人类受试者的医学图像，3D打印将用于提供几十个逼真的上气道复制品。使用自动化设计方法，耦合计算流体动力学模拟与优化，我们将开发理想化的上气道几何形状，填补上述空白。这些理想化上气道中的颗粒沉积的实验测量将允许这些气道的微调，最终验证理想化上气道与现实气道中的颗粒沉积相比模拟平均颗粒沉积的能力。 拟议的工作将提供所需的工具，以实现一个几乎完整的了解上气道颗粒沉积。鉴于对颗粒物暴露增加的影响以及通过呼吸道治疗和预防疾病的关注日益增加，拟议的工作解决了我们知识和能力方面的重要差距，并为改善治疗和风险暴露评估铺平了道路，特别是在儿童中。

Particles in the air that we breathe are a major source of detrimental health effects. On the other hand, the intentional delivery of airborne particles to the respiratory tract is an important method of delivering therapeutic drugs for the treatment of diseases e.g. asthma, flu and rhinitis, among many others. For these reasons, understanding and predicting the behavior of particles in the respiratory tract is important both for assessing the risks associated with ambient aerosol exposure, but also for improving treatments that rely on drug delivery to the respiratory tract. Because inhaled particles must enter the respiratory tract through the nose or mouth (the so-called upper airways), understanding the fate of such particles begins with understanding their fate in the upper airways. Over the span of more than two decades, the Aerosol Research Laboratory of Alberta (ARLA) has methodically explored particle behavior in the upper airways, leading to our development of idealized upper airway physical models that are now used by many academic researchers and more than 40 companies in Canada and worldwide for research on aerosol exposure and in the development and testing of inhalers. Despite this success, several major gaps exist in our ability to assess upper airway deposition in vitro. One of these gaps includes a lack of idealized upper airway models that mimic nanoparticle deposition. A second gap is the lack of an idealized model that mimics oral deposition of micrometer diameter particles in preschool children. The final gap is the lack of idealized nasal airways for mimicking the deposition of nasal-administered sprays. We propose to fill these gaps by first performing extensive experiments and simulations of the behavior of aerosols and sprays in replicas of the upper airways of human subjects. Using medical images of approximately a dozen human subjects in each of several age ranges from birth to adulthood, 3D printing will be used to give several dozen realistic upper airway replicas. Using automated design methods that couple computational fluid dynamics simulations with optimization, we will develop idealized upper airway geometries that fill the above noted gaps. Experimental measurement of particle deposition in these idealized upper airways will allow fine tuning of these airways, culminating in validation of the ability of idealized upper airways to mimic average particle deposition compared to that in the realistic airways. The proposed work will provide the tools needed to achieve a nearly complete understanding of upper airway particle deposition. Given increasing concerns regarding the effects of increased particulate exposure and the treatment and prevention of disease via the respiratory tract, the proposed work addresses essential gaps in our knowledge and abilities, and paves the way to allowing improved treatment and risk exposure assessment, particularly in children.