Engineering Ventilation Waveforms to Reduce Atelectrauma

描述（由申请人提供）：该项目的目标是确定有前途的小容量通气波形，该波形将打开闭塞的肺气道，同时对敏感上皮组织的损伤最小。这个问题在生理学上是重要的，因为由粘性液体阻塞引起的肺气道阻塞发生在多种疾病中，包括呼吸窘迫综合征（RDS）、急性呼吸窘迫综合征（ARDS）和哮喘。气道关闭通过减少气体输送导致的通气-灌注失配导致死亡。在RDS和潜在的ARDS中，由于表面活性剂缺乏，衬里流体表面张力升高，这增加了打开闭塞气道所需的压力。本研究将验证这样一个假设，即脉冲通气波形可以通过最大化表面活性剂运输和优化生物物理反应来减少气道上皮的损伤机械应力，从而最大限度地减少对气道上皮的损伤。每个特定目标将计算模拟与实验室实验相结合，以阐明在一指空气通过圆柱形管作为模型系统的迁移过程中，机械应力、传输特性、表面活性剂生物物理反应和细胞损伤之间的相互作用。该项目的具体目标是：具体目标#1：测试预测上皮细胞被气道重开期间扫过细胞的瞬时压力梯度损伤，并确定稳定和脉动流的刺激/反应行为。具体目标#2：研究表面活性剂生物物理特性与界面流波形耦合可以保护上皮的预测，并使用这些研究得出的原理来预测通气波形的特性，这些波形将在对气道上皮损伤最小的情况下招募阻塞的气道。本课题的成功完成将有助于提高对通气在肺损伤中的作用的认识。根据本研究得出的原则改进的通气方案可以降低患有呼吸窘迫综合征或哮喘的婴儿和成人的死亡率。

DESCRIPTION (provided by applicant): The goal of this project is to identify promising low-volume ventilation waveforms that will open occluded pulmonary airways with minimal damage to sensitive epithelial tissue. This problem is physiologically significant because the obstruction of pulmonary airways by a viscous liquid occlusion occurs in a variety of diseases including respiratory distress syndrome (RDS), acute respiratory distress syndrome (ARDS) and asthma. Airway closure contributes to mortality through ventilation-perfusion mismatch from reduced gas transport. In RDS and potentially ARDS, the lining fluid surface tension is elevated due to surfactant deficiency, which increases the pressure necessary to open the occluded airways. The proposed studies will test the hypothesis that pulsatile ventilation waveforms can be used to minimize damage to airway epithelial cells by maximizing surfactant transport and optimizing biophysical responses to reduce the damaging mechanical stress imparted on airway epithelium. Each specific aim couples computational simulations to laboratory experiments to elucidate the interactions between mechanical stresses, transport properties, surfactant biophysical responses and cell damage during the migration of a finger of air through a cylindrical tube as the model system. The specific aims of the project are: Specific Aim #1: Test the prediction that epithelial cells are wounded by the transient pressure gradient that sweeps across the cells during airway reopening and determine the stimulus/response behavior for steady and pulsatile flows. Specific Aim #2: Investigate the prediction that surfactant biophysical properties coupled to interfacial flow waveforms can protect the epithelium, and use the principles derived from these studies to predict properties of ventilation waveforms that will recruit an obstructed airway with minimal damage to the airway epithelium. Successful completion of this project will lead to improved understanding of the role of ventilation on lung injury. Improved ventilation protocols resulting from the principles derived from this study could lead to reduced mortality of infants and adults suffering from respiratory distress syndrome or asthma.