Engineering Ventilation Waveforms to Reduce Atelectrauma

描述（由申请人提供）：本项目的目标是确定有前景的低容量通气波形，该波形将打开闭塞的肺气道，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，因为粘性液体阻塞导致的肺气道阻塞发生在包括呼吸窘迫综合征（RDS）、急性呼吸窘迫综合征（ARDS）和哮喘在内的多种疾病中。由于气体转运减少导致通气-灌注不匹配，气道关闭导致死亡。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，这增加了打开阻塞气道所需的压力。拟议的研究将测试的假设，脉动通气波形可用于最大限度地减少损伤气道上皮细胞，最大限度地提高表面活性剂的运输和优化生物物理反应，以减少破坏性的机械应力赋予气道上皮。每个具体的目标耦合计算模拟实验室实验，以阐明机械应力，运输性能，表面活性剂的生物物理反应和细胞损伤之间的相互作用，在迁移的手指空气通过一个圆柱形管作为模型系统。该项目的具体目标是：具体目标#1：测试上皮细胞在气道重新开放过程中受到瞬时压力梯度的伤害的预测，并确定稳定和脉动流的刺激/反应行为。具体目标#2：调查预测，表面活性剂的生物物理特性耦合到界面流波形可以保护上皮，并使用从这些研究中得出的原则来预测通气波形的属性，这将招募阻塞的气道，对气道上皮的损伤最小。本项目的成功完成将导致更好地理解通气对肺损伤的作用。从这项研究中得出的原则所产生的改进的通气协议可能会导致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.