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

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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.**