Lung protection with high frequency ventilation

高频通气保护肺部

• 批准号: 6820141
• 负责人: Roy G. Brower
• 金额: $ 5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6820141
• 关键词: adult respiratory distress syndrome; biomarker; clinical trials; dogs; high frequency ventilation; human subject; human therapy evaluation; iatrogenic disease; lung injury; pathologic process; patient oriented research; positive pressure breathing; respirators

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.

机械通气（MV）提供了维持生命的支持，这对于恢复大多数急性肺损伤患者（全部）至关重要。但是，MV本身可能导致肺损伤（通风相关的肺损伤，Vali）。这可能会延迟或防止因败血症等可治疗条件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并改善所有患者的临床结果。该项目是此SCCOR应用程序的关键组成部分，该项目代表了识别Vali的分子机制，然后将新知识转化为的综合方法 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所有患者，但是在建议HFOV推荐广泛使用之前，必须解决一些问题。项目1领导者Roy Brower，医学博士领导了几项临床试验，这些试验已经确定了当前使用常规机械通气的当前标准。 Brett Simon，M.D。Ph.D.是项目共同领导者，是一位创新而有成就的生物医学工程师和生理学家，他为了解HFOV的生理学做出了一些贡献。西蒙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部力学和气体交换的影响。项目1调查人员将使用最先进的 艺术临床，成像和分子工具以及新的表型工具，以建立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瓦利已知生物标志物的影响，并确定瓦利发病机理中新型的分子途径。特定目标2中的实验将表征HFOV设置与所有患者的特定生理特征之间的相互作用。从特定目标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。特定目标3包括一项探索性临床试验，该试验比较接受优化的HFOV或优化常规MV方法的患者疗效和安全性的临床和生理指标。这些研究的完成将 提供有关Vali发病机理的见解，并将指导未来的机械和临床研究，旨在改善所有患者的临床结果。