Determining the Effect of Airway Deformation on Pulmonary Air-Particle Dynamics

慢性阻塞性肺疾病（COPD）是美国第四大死亡原因，由于气道僵硬、气道变形能力丧失和炎症引起的气道阻塞，导致严重的呼吸困难。吸入治疗性微颗粒是标准的COPD药物治疗，但由于气道收缩，长期存在递送障碍，无法达到预期的治疗效果。具体来说，只有不到25%的颗粒可以到达远端气道，大部分颗粒沉积在上呼吸道。该项目将使用计算流体动力学代码来更好地理解疾病特异性气道变形运动学对肺空气颗粒流动动力学的作用。通过调节颗粒大小、吸湿性生长和吸气流条件，寻求最佳的输送方法来控制肺空气颗粒运输，并实现目标颗粒输送到远端气道。该项目还包括外展内容，以普及“计算机肺保健”的概念，并增加代表性不足群体的STEM参与。该项目的目标是模拟和量化copd特定气道变形运动学对(a)改变上气道的涡流结构和肺气道树的再分层化以及(b)随后改变小气道中的颗粒混合效果和颗粒输送效率的影响。该项目将开发一种新的基于计算的弹性全肺建模框架，以捕获疾病特异性气道变形运动学，同时捕获全肺中的空气颗粒流预测。该项目将(i)开发、校准和验证弹性全肺模型，以捕获严重COPD肺病的气道变形运动学；（ii）量化疾病特异性气道变形运动学对肺空气颗粒运输动力学和沉积的影响；（iii）量化颗粒特征和呼吸方式对远端气道空气颗粒运输、沉积机制和输送效率的影响。该研究将促进我们对全肺血流动力学的了解，了解特定疾病的气道变形运动学如何影响肺部气流和吸入颗粒的运输、分布和沉积。新的弹性全肺建模框架和对疾病特异性肺空气颗粒传输动力学的增强理解将有助于实现个性化吸入治疗优化，以改善治疗结果并减少副作用。该项目由流体动力学项目和促进竞争研究的既定项目（EPSCoR）共同资助。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。

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in America, causes severe breathing difficulty due to airway stiffening, loss of airway deformation capability, and airway blockage induced by inflammation. Inhalation of therapeutic micro particles is the standard COPD drug treatment, but it has a long-standing delivery barrier to achieving desired therapeutic outcomes because of airway constriction. Specifically, less than 25% of the particles can reach the distal airways, with most of the particles depositing in the upper airway. The project will use a computational fluid dynamics code to better understand the role of disease-specific airway deformation kinematics on pulmonary air-particle flow dynamics. By modulating particle size, hygroscopic growth, and inspiratory flow conditions, an optimal delivery approach will be sought to control the pulmonary air-particle transport and achieve targeted particle delivery to distal airways. The project also entails outreach components to popularize the concepts of “in silico pulmonary healthcare” and increase STEM engagement of underrepresented groups.The goal of the project is to simulate and quantify the influence of COPD-specific airway deformation kinematics on (a) altering the vortex structures in the upper airway and the relaminarization in the lung airway tree and (b) subsequently altering the particle mixing effects and particle delivery efficiency in small airways. The project will develop a new computation-based elastic whole-lung modeling framework to capture the disease-specific airway deformation kinematics simultaneously with the air-particle flow predictions in the whole lung. The project will (i) develop, calibrate, and validate the elastic whole-lung model to capture the airway deformation kinematics for severe COPD lung condition; (ii) quantify the effect of disease-specific airway deformation kinematics on pulmonary air-particle transport dynamics and deposition; and (iii) quantify the effects of particle characteristics and breathing pattern on air-particle transport and deposition mechanisms and delivery efficiency in distal airways. The research will advance our knowledge of whole-lung flow dynamics on how disease-specific airway deformation kinematics can influence the pulmonary airflow and inhaled particle transport, distribution, and deposition. The new elastic whole-lung modeling framework and enhanced understanding of the disease-specific pulmonary air-particle transport dynamics will help achieve personalized inhalation therapy optimization for improved therapeutic outcomes with reduced side effects. This project is jointly funded by Fluid Dynamics program and the Established Program to Stimulate Competitive Research (EPSCoR).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.