RAPID: Characterization of Aerosolized Droplet and Droplet Nuclei in Cough

由于有证据表明病毒通过雾化飞沫在宿主与宿主之间传播，因此人们对咳嗽产生的飞沫在环境中的行为非常感兴趣。以前的研究主要集中在这些液滴如何与外部环境相互作用上，而对它们在体内的行为却知之甚少。然而，飞沫在气道内的行为在很大程度上决定了它们在体外的后续特征（如大小和弥散度），以及它们在体内滞留导致肺部感染、肺炎、误吸和死亡的可能性。同样不清楚的是，如果咳嗽太弱，无法排出携带病毒的飞沫，人们患肺部感染和肺部肺炎的风险是否会更大，这在某些已有疾病的情况下可能会发生。该多学科研究项目的目标是将计算模型与实验相结合，以充分了解雾化咳嗽飞沫在人体气道内根据咳嗽强度的行为，并评估携带病毒的飞沫在气道中保留或传播到肺部的可能性。该研究成果将对减少新冠病毒传播、减少住院、减少死亡的技术开发具有临床意义。对气道内液滴行为的关注将与阐明新的COVID-19菌株的行为特别相关，这些菌株已被发现在气道中产生比原始菌株更高的病毒载量，使新菌株对其他菌株更具传染性。这项研究将能够确定这些新变异在气道中停留的时间，这将有助于开发减少它们在体外传播的技术。这项研究的一个重要组成部分也是教育下一代科学家和工程师，特别是那些来自代表性不足的群体的科学家和工程师，为他们提供机会，使他们有机会研究具有挑战性的具有公共卫生意义的多学科问题。自2019冠状病毒病大流行以来，大多数研究都集中在携带病毒的咳嗽飞沫与周围环境的相互作用上，这是可以理解的。然而，飞沫在气道内的行为在很大程度上决定了它们在体外的后续特征（如大小和传播距离），以及它们在体内滞留导致肺部感染、肺炎、误吸和死亡的可能性。咳嗽强度在携带新病毒株的飞沫滞留在气道内的作用也没有得到充分探讨，这些飞沫可能导致一系列环境传播。这个多学科研究项目的目标是将计算流体动力学与实验相结合，以充分表征雾化液滴和纳米颗粒在人类上呼吸道内相对于咳嗽强度的行为。模型校准和验证的实验将利用一种新型体积打印工艺生产的逼真的三维打印上呼吸道结构。在结构中模拟咳嗽，将荧光素溶液雾化产生种子液滴。液滴大小将量化使用蓝光滤光片和内窥镜图像的数字图像处理。该研究将：(a)量化小液滴和纳米颗粒在佩戴和不佩戴标准口罩的受试者中与气道的相互作用；(b)在正常和紊乱咳嗽功能下，量化气道内液滴特征（大小分布、停留时间、轨迹）；(c)量化相对于咳嗽强度的飞沫吸入能力和延迟传播潜力；(d)利用实验数据验证计算模型。通过建立液滴和纳米颗粒与咳嗽流和气道相互作用的基本特征，本项目将提供表征复杂纳米颗粒在咳嗽流特别是瞬态爆炸流条件下的行为的策略。项目成果将与临床相关的技术开发，以尽量减少COVID-19的传播，住院和死亡。关注气道内的颗粒行为将与探索新的COVID-19毒株的行为特别相关，这些毒株已被发现在鼻腔和口腔中产生比原始毒株更高的病毒载量，使新毒株对其他毒株更具传染性。开发的模型将能够量化这些新变体的停留时间，并探索干预技术，以减轻它们在体外传播或吸入性肺炎和肺部感染的可能性。随着人们对covid - 19后患者的长期影响有了更好的了解，相对于咳嗽强度的飞沫行为将成为一个重要的风险标志，因为保留在肺组织中的微愿望可能导致肺部感染、肺炎或死亡。covid - 19后患者出现的症状和其他合并症的顺序放大了正在调查的误吸事件的重要性。这项研究还将有助于开发呼吸干预技术，以改善中风后、久坐的老年人或接受过癌症相关治疗的患者的咳嗽功能缺陷。这项研究的教育目标将侧重于教育下一代科学家和工程师，特别是那些来自代表性不足群体的科学家和工程师，为他们提供机会，研究具有公共卫生意义的具有挑战性的多学科问题。研究成果将直接整合到pi教授的两门本科课程和两门研究生课程中。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

There is considerable interest in the behavior of cough-generated droplets in the environment due to evidence of host-to-host transmission of viruses through aerosolized droplets. Previous investigations have mostly focused on how such droplets interact with the external environment and not much has been explored on their behavior inside the body. Yet, the droplet behavior inside the airway largely determines their subsequent characteristics outside the body (such as size and dispersion), as well as their potential for retention inside the body to cause lung infection, pneumonia, aspiration, and mortality. It is also unknown whether people are at greater risk for pulmonary infection and pulmonary pneumonia if their cough is too weak to expel virus-laden droplets as may occur under some pre-existing conditions. The objective of this multidisciplinary research project is to combine computational modeling with experiments to fully understand the behavior of aerosolized cough droplets inside the human airway depending on the cough strength and assess the potential of virus-laden droplets to be retained in the airway or transmitted to the lungs. The research outcome will be clinically relevant to the development of technologies to minimize the spread of COVID-19, hospitalization, and death. The focus on droplet behavior inside the airway will be particularly relevant for elucidating the behavior of new COVID-19 strains which have been found to generate higher viral loads in the airway compared to the original strain, making the new strains much more contagious to others. The research will enable determination of how long these new variants reside in the airway, which will aid in the development of technologies that mitigate their potential transmission outside the body. An important component of the research is also the education of the next generation of scientists and engineers, especially those from under-represented groups by providing them an opportunity to work on a challenging multidisciplinary problem of public health significance.Since the advent of the COVID-19 pandemic, most studies have understandably focused on the interaction of virus-laden cough droplets with the ambient environment. Yet, the behavior of droplets inside the airway largely determines their subsequent characteristics outside the body (such as size and transmission distance), as well as their potential for retention inside the body to cause lung infection, pneumonia, aspiration, and mortality. The role of cough strength in the retention of droplets laden with the new viral strains inside the airway with potential to cause serial environmental transmission has also not been fully explored. The objective of this multidisciplinary research project is to integrate Computational Fluid Dynamics with experiments to fully characterize the behavior of aerosolized droplets and nanoparticles relative to cough strength inside the human upper airway. The experiments for model calibration and validation will utilize a realistic three-dimensional-printed upper airway structure produced with a novel volumetric printing process. Cough will be simulated in the structure with fluorescein solution atomized to produce seed droplets. Droplet sizes will be quantified using a blue-light filter and digital image processing of endoscope images. The research will: (a) Quantify small droplet and nanoparticle interaction with the airway, in subjects with and without standard facemask; (b) Quantify droplet characteristics (size distribution, residence time, trajectories) within the airway under normal and disordered cough functions; (c) Quantify aspiration capacity and delayed transmission potential of droplets relative to cough strength; and (d) Validate the computational models using the experimental data. By establishing the fundamental features of droplet and nanoparticle interaction with cough flow and the airway, this project will deliver the strategies for characterization of complex nanoparticle behavior under cough flow in particular and transient explosive flow condition in general. The project outcome will be clinically relevant in the development of technologies to minimize the spread of COVID-19, hospitalization, and death. The focus on particle behavior inside the airway will be particularly relevant to exploring the behavior of new COVID-19 strains which have been found to generate higher viral loads in the nasal and oral cavities compared to the original strain, making the new strains much more contagious to others. The model developed will enable quantification of the residence times of these new variants and explore intervention technologies to mitigate their potential for transmission outside the body or aspiration pneumonia and lung infection. As the longer-term impact of post-COVID patients becomes better understood, the droplet behavior relative to cough strength will be an important risk marker as the micro aspirations that retain in the lung tissue can result in lung infection, pneumonia, or death. The sequence of symptoms and other comorbidities occurring in post-COVID patients amplify the significance of the aspiration event being investigated. This research will also assist the development of respiratory intervention technologies to improve deficits of cough function in patients with pre-existing conditions such as post-stroke individuals, sedentary elderly or those who have undergone cancer related treatment. The education objective of the research will focus on educating the next generation of scientists and engineers, especially those from under-represented groups by providing them an opportunity to work on a challenging multidisciplinary problem of public health significance. The research findings will be integrated directly in two undergraduate courses and two graduate courses taught by the PIs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.