Lung protection with high frequency ventilation

机械通气（MV）提供对于大多数急性肺损伤（AL 1）患者的恢复至关重要的生命维持支持。然而，MV本身可能导致肺损伤（通气相关性肺损伤，VALI）。这可能会延迟或阻止由可治疗的疾病（如败血症）引起的急性呼吸衰竭的恢复。项目1旨在开发更好的MV技术，以减少VALI并改善ALL患者的临床结局。该项目是SCCOR应用程序的关键组成部分，它代表了识别VALI分子机制的综合方法，然后将新知识转化为 改善临床护理。该SCCOR项目的重点是高频振荡通气（HFOV）。该技术最近可用于成人ALL患者，但在推荐广泛使用HFOV之前必须解决几个问题。项目1负责人罗伊·布劳尔，医学博士。已经领导了几项临床试验，这些临床试验已经建立了在AL 1中使用常规机械通气的当前标准。Brett Simon，医学博士哲学博士、项目共同负责人，是一个创新和有成就的生物医学工程师和生理学家谁作出了几个贡献，了解HFOV的生理。Simon开发了复杂的成像工具和大型动物模型，用于研究临床干预对ALL中肺力学和气体交换的影响。项目1调查人员将使用 最新的临床、成像和分子工具以及新的表型分析仪器，以确定HFOV的临床价值。特定目标1中的实验将表征不同机械通气策略对VALI已知生物标志物的影响，并确定VALI发病机制中的新分子途径。特定目标2中的实验将表征HFOV设置与ALL 1患者的特定生理特征之间的相互作用。从具体目标1和2中获得的知识将提供优化HFOV和常规MV方法所需的关键信息。具体目标3包括一项探索性临床试验，旨在比较接受优化HFOV或优化传统MV入路的患者的有效性和安全性的临床和生理指标。完成这些研究将 提供了关于VALI发病机理的见解，并将指导未来旨在改善ALL患者临床结果的机制和临床研究。

Mechanical ventilation (MV) provides life-sustaining support that is essential for recovery of most patients with acute lung injury (ALl). However, MV may itself cause lung injury (ventilation-associated lung injury, VALI). This may delay or prevent recovery from acute respiratory failure caused by treatable conditions such as sepsis. Project 1 is designed to develop better techniques of MV to reduce VALI and improve clinical outcomes of ALl patients. This project is a key component of this SCCOR application, which represents an integrated approach to identifying molecular mechanisms of VALI and then translating new knowledge into improved clinical care. The focus of this SCCOR project is high frequency oscillatory ventilation (HFOV). This technology recently became available for use in adult ALl patients, but several issues must be addressed before HFOV can be recommended for widespread use. The Project 1 leader, Roy Brower, M.D. has led several clinical trials that have established the current standard for using conventional mechanical ventilation in ALl. Brett Simon, M.D. Ph.D., project co-leader, is an innovative and accomplished biomedical engineer and physiologist who has made several contributions to understanding the physiology of HFOV. Simon has developed sophisticated imaging tools and large animal models for studying effects of clinical interventions on lung mechanics and gas exchange in ALl. The Project 1 investigators will use state-of-the art clinical, imaging, and molecular tools and novel phenotyping instruments to establish the clinical value of HFOV. Experiments in Specific Aim 1 will characterize effects of different mechanical ventilation strategies on known biomarkers of VALI and also identify novel molecular pathways in VALI pathogenesis. Experiments in Specific Aim 2 will characterize the interactions between HFOV settings and specific physiologic characteristics of ALl patients. Knowledge gained from Specific Aims 1 and 2 will provide critical information needed to optimize HFOV and conventional MV approaches. Specific Aim 3 consists of an exploratory clinical trial to compare clinical and physiologic indicators of efficacy and safety in patients who receive either an optimized HFOV or optimized conventional MV approach. Completion of these studies will provide insights regarding pathogenesis of VALI and will guide future mechanistic and clinical studies designed to improve clinical outcomes in ALl patients.