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

我们的肺包含一个分叉的呼吸道网络。肺的稳定性和正常的呼吸是由一种名为表面活性物质的天然物质维持的。大多数早产儿的肺不发达，缺乏表面活性物质，使新生儿呼吸非常困难。这些婴儿经常接受一种治疗，包括向他们的气管内注入表面活性物质溶液。来自呼吸机的气流然后被用来将溶液引导到肺部的呼吸道。这种治疗的成功在很大程度上取决于表面活性物质在呼吸道中分布的均匀性。然而，来自X射线成像的证据显示，表面活性物质分布不均匀，导致对治疗的反应不佳。由于无法进入呼吸道，改善这种治疗及其有效性已被证明是困难的。这个项目将使用实验和模拟相结合的方法来解决这个悬而未决的问题。我们将设计现实的人类肺气道模型，利用它们来研究表面活性物质向肺部的输送，并确定导致表面活性物质均匀分布的输送条件，从而使治疗更有效。除了通过外展项目为学生提供培训机会和促进多样性之外，我们的项目还将通过开发新工具和阐明肺部呼吸道中的液体流动来产生变革性的影响。本项目的总体目标是了解表面活性物质在导管区呼吸道中输送和分布的流体动力学。使用一套设计规则，我们生成了呼吸道树的三维计算模型，并采用加法制造的方法制作了它们。然后，我们将使用互补的实验和计算研究来定量地阐明流体类型(牛顿和非牛顿表面活性剂)、气流类型(恒定和循环)以及气道树的重力方向如何影响表面活性物质在呼吸道中的沉积和分布。我们将通过两个具体的目标来实现这一目标：(I)定量研究恒定气流下表面活性物质在肺气道树中的分布；(Ii)循环气流和预先存在的表面活性物质膜对表面活性物质分布的影响。这项工作将对对肺内多相流流体动力学的基本理解产生革命性的影响，并导致设计增强表面活性物质替代疗法的策略。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.