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影响的主要来源。另一方面，故意将空气中的颗粒输送到呼吸道是输送治疗药物的一种重要方法，用于治疗哮喘、流感和鼻炎等疾病。出于这些原因，了解和预测呼吸道中颗粒物的行为对于评估与环境气雾剂暴露相关的风险，以及改进依赖于呼吸道药物输送的治疗方法都是重要的。因为吸入的颗粒物必须通过鼻子或口腔(所谓的上呼吸道)进入呼吸道，所以要了解这些颗粒物的命运，首先要了解它们在上呼吸道的命运。在二十多年的时间里，艾伯塔省气溶胶研究实验室(ARLA)有条不紊地探索了上呼吸道中的颗粒行为，导致我们开发出了理想化的上呼吸道物理模型，现在许多学术研究人员和加拿大及世界各地的40多家公司都在使用该模型进行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，但在我们评估体外上呼吸道沉积的能力方面仍存在几个主要差距。其中一个差距包括缺乏模拟纳米颗粒沉积的理想化上呼吸道模型。第二个差距是缺乏一个理想的模型来模拟学龄前儿童微米直径颗粒的口腔沉积。最后一个缺口是缺乏理想的鼻腔呼吸道来模拟鼻腔给药喷雾剂的沉积。我们建议通过首先对人体上呼吸道的气雾剂和喷雾剂的行为进行广泛的实验和模拟来填补这些空白。使用从出生到成年的几个年龄段的大约12名人类受试者的医学图像，3D打印将被用来制作几十个逼真的上呼吸道复制品。使用将计算流体力学模拟与优化相结合的自动化设计方法，我们将开发出填补上述空白的理想化上呼吸道几何形状。对这些理想化上呼吸道中颗粒沉积的实验测量将允许对这些气道进行微调，最终验证理想上呼吸道与现实气道相比模拟平均颗粒沉积的能力。 这项拟议的工作将提供所需的工具，以实现对上呼吸道颗粒沉积的几乎完全的了解。鉴于人们对增加接触颗粒物以及通过呼吸道治疗和预防疾病的影响日益关切，拟议的工作填补了我们在知识和能力方面的根本差距，并为改进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.