Collaborative Research: Integrated experimental and computational investigations of exogenous surfactant distribution in conducting zone lung airways

我们的肺里有一个气管分支网络。肺的稳定和正常呼吸是由一种叫做表面活性剂的天然物质维持的。大多数早产儿的肺部发育不全，缺乏表面活性剂，使得新生儿呼吸非常困难。这些婴儿通常接受的治疗包括将表面活性剂溶液注入气管。然后使用呼吸机的气流引导溶液进入肺气道。这种治疗的成功很大程度上取决于表面活性剂在气道内分布的均匀性。然而，x射线成像显示表面活性剂分布不均匀，导致治疗效果不佳。由于气道的不可达性，改善这种治疗方法及其有效性已被证明是困难的。本项目将通过实验和模拟相结合的方法来解决这个尚未解决的问题。我们将设计真实的人体肺气道模型，用它们来研究表面活性剂向肺部的输送，并确定导致表面活性剂均匀分布的输送条件，从而使治疗更有效。除了为学生提供培训机会和通过外展项目促进多样性外，我们的项目还将通过开发新工具和阐明肺气道中的流体流动产生变革性影响。本项目的总体目标是了解表面活性剂在导电带气道中的输送和分布的流体动力学。利用一套设计规则，生成气道树的三维计算模型，并利用增材制造技术进行制造。然后，我们将使用互补的实验和计算研究来定量阐明流体类型（牛顿和非牛顿表面活性剂）、气流类型（恒定vs循环）和气道树的重力方向如何影响表面活性剂在气道中的沉积和分布。我们将通过两个具体目标来实现这一目标：(i)定量研究恒气流下表面活性剂在肺气道树中的分布；循环气流和已有表面活性剂膜对表面活性剂分布的影响。这项工作将对对肺气道多相流流体动力学的基本理解产生变革性影响，并导致设计增强表面活性剂替代治疗的策略。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。

Our lungs contain a branching network of airways. Lung stability and normal breathing is maintained by a natural substance called surfactant. The lungs of most premature babies are underdeveloped and lack surfactant, making breathing very difficult for the newborn. These babies often receive a treatment that involves instilling a surfactant solution into their windpipe. Airflow from a ventilator is then used to direct the solution into the lung airways. The success of this treatment heavily depends on the uniformity of distribution of surfactant in airways. However, evidence from x-ray imaging shows non-uniform surfactant distribution, leading to a poor response to the treatment. Improving this treatment and its effectiveness has proved difficult due to inaccessibility of airways. This project will address this unresolved issue by using a combined experimental and simulation approach. We will design realistic models of human lung airways, use them to study surfactant delivery to the lungs, and determine delivery conditions that lead to a uniform surfactant distribution, thereby making the treatment more effective. In addition to providing training opportunities to students and promoting diversity through outreach programs, our project will also make a transformative impact through developing new tools and elucidating fluid flow in lung airways.The overarching goal of this project is to understand fluid dynamics of surfactant delivery and distribution in conducting zone airways. Using a set of design rules, we generate 3D computational models of airway tree and fabricate them using additive manufacturing. We will then use complementary experimental and computational studies to quantitatively elucidate how fluid type (Newtonian and non-Newtonian surfactants), airflow type (constant vs cyclic), and gravitational orientation of the airway tree affect surfactant deposition and distribution in airways. We will achieve this goal through two specific aims: (i) Quantitatively study surfactant distribution in lung airway tree under constant airflow; and (ii) Cyclic airflow and pre-existing surfactant film effects on surfactant distribution. This work will make a transformative impact on fundamental understanding of fluid dynamics of multi-phase flow in lung airways and lead to design of strategies to enhance surfactant replacement therapy.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.