Lung protection with high frequency ventilation

机械通气(MV)为大多数急性肺损伤(ALL)患者的康复提供必要的生命支持。然而，机械通气本身也可能引起肺损伤(VALI)。这可能会延缓或阻止败血症等可治疗疾病引起的急性呼吸衰竭的恢复。项目1旨在开发更好的机械通气技术，以减少VALI并改善所有患者的临床结果。这个项目是SCCOR应用程序的关键组成部分，它代表了一种识别VALI分子机制的集成方法，然后将新知识转化为 改善临床护理。本SCCOR项目的重点是高频振荡通风(HFOV)。这项技术最近可用于成人所有患者，但在HFOV推荐广泛使用之前，必须解决几个问题。项目1的负责人、医学博士罗伊·布劳尔领导了几项临床试验，这些试验确立了目前使用常规机械通气的所有标准。布雷特·西蒙，医学博士，项目共同负责人，是一位富有创新精神和成就的生物医学工程师和生理学家，他为理解HFOV的生理学做出了多项贡献。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肺力学和气体交换的影响。项目1调查员将使用最新的 ART临床、成像和分子工具以及新的表型仪器，以确定HFOV的临床价值。具体目的1的实验将表征不同的机械通气策略对VALI已知生物标志物的影响，并确定VALI发病机制中的新的分子途径。特定目标2的实验将描述HFOV设置与所有患者的特定生理特征之间的相互作用。从具体目标1和2获得的知识将提供优化HFOV和传统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，以比较接受优化HFOV或优化传统MV治疗的患者的临床和生理指标的有效性和安全性。完成这些研究后， 提供有关VALI发病机制的见解，并将指导未来旨在改善所有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.