RAPID: Characterization of Aerosolized Droplet and Droplet Nuclei in Cough

RAPID：咳嗽中雾化液滴和液滴核的表征

• 批准号: 2153814
• 负责人: Olusegun Ilegbusi
• 金额: $ 19.99万
• 依托单位: The University of Central Florida Board of Trustees
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2153814&HistoricalAwards=false
• 关键词: RAPID; Characterization; Aerosolized; Droplet; Nuclei

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.

由于有证据表明病毒通过雾化飞沫在宿主之间传播，因此人们对环境中咳嗽产生的飞沫的行为非常感兴趣。之前的研究主要集中在这些液滴如何与外部环境相互作用，而对它们在体内的行为却没有太多探索。然而，气道内的飞沫行为在很大程度上决定了它们在体外的后续特性（例如大小和分散性），以及它们滞留在体内导致肺部感染、肺炎、误吸和死亡的可能性。目前还不清楚，如果人们的咳嗽太弱而无法排出载有病毒的飞沫，那么他们是否会面临更大的肺部感染和肺部肺炎的风险，而在某些已有的情况下可能会发生这种情况。 这个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呼吸道内的行为，具体取决于咳嗽强度，并评估载有病毒的飞沫保留在气道中或传播到呼吸道的可能性。肺部。研究成果将在临床上与技术开发相关，以最大限度地减少 COVID-19 的传播、住院和死亡。对气道内飞沫行为的关注对于阐明新的 COVID-19 毒株的行为特别重要，人们发现与原始毒株相比，新毒株在气道中产生更高的病毒载量，从而使新毒株对其他毒株的传染性更强。这项研究将能够确定这些新变种在气道中停留的时间，这将有助于开发减轻其潜在的体外传播的技术。该研究的一个重要组成部分也是对下一代科学家和工程师的教育，特别是那些来自代表性不足群体的科学家和工程师，为他们提供机会来研究具有公共卫生意义的具有挑战性的多学科问题。自新冠病毒出现以来， 19 流感大流行期间，大多数研究都集中在载有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（例如大小和传播距离），以及它们滞留在体内导致肺部感染、肺炎、误吸和死亡的可能性。咳嗽强度在气道内滞留携带新病毒株的飞沫中的作用也尚未得到充分探索，这些飞沫可能导致连续的环境传播。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相对于人体上呼吸道内咳嗽强度的行为。模型校准和验证实验将利用通过新颖的体积打印工艺生产的真实三维打印上呼吸道结构。荧光素溶液雾化产生种子液滴，在结构中模拟咳嗽。将使用蓝光滤光片和内窥镜图像的数字图像处理来量化液滴尺寸。该研究将： (a) 量化带或不带标准口罩的受试者中小液滴和纳米颗粒与气道的相互作用； (b) 量化正常和紊乱咳嗽功能下气道内的液滴特征（尺寸分布、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) 使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，该项目将提供表征咳嗽流（特别是咳嗽流）和一般瞬态爆炸流条件下复杂纳米颗粒行为的策略。该项目的成果将与技术开发具有临床相关性，以最大限度地减少 COVID-19 的传播、住院和死亡。对气道内颗粒行为的关注将与探索新的 COVID-19 毒株的行为特别相关，与原始毒株相比，新毒株被发现在鼻腔和口腔中产生更高的病毒载量，从而使新毒株更具传染性给其他人。开发的模型将能够量化这些新变种的停留时间，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。 随着人们更好地了解新冠肺炎后患者的长期影响，与咳嗽强度相关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量吸入可能导致肺部感染、肺炎或死亡。 新冠肺炎后患者出现的一系列症状和其他合并症增强了所调查的误吸事件的重要性。这项研究还将协助开发呼吸干预技术，以改善患有既往疾病的患者（例如中风后患者、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。该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，为他们提供解决具有公共卫生意义的挑战性多学科问题的机会。研究结果将直接融入由 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 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。