Aerosol Ventilation to Reduce Ventilator Induced Lung Injury

气雾通气可减少呼吸机引起的肺损伤

基本信息

批准号：
10383334
负责人：
Andrew Jones
金额：
$ 30万
依托单位：
BOUNDLESS SCIENCE, LLC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-23 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383334
关键词：
Acute Respiratory Distress Syndrome Aerosols Air Alveolar Alveolus Anti-Inflammatory Agents Antiinflammatory Effect Apoptosis Automobile Driving Biopsy Cannulations Carbon Dioxide Carrying Capacities Cell Line Cells Clinical Couples Therapy Development Devices Endothelium Endotoxins Epithelial Epithelial Cells Equipment Excision Exhalation Extracorporeal Membrane Oxygenation Family suidae Fluorocarbons Functional disorder Gases Goals Guidelines Hemorrhage Human Image In Vitro Inflammation Inflammatory Inflammatory Response Inhalation Injury Intervention Intubation Lead Liquid substance Lung Magnetic Resonance Imaging Measures Mechanical Ventilators Mechanical ventilation Medical Medical Device Methods Minor Monitor Morbidity - disease rate Necrosis Oxygen Partial Liquid Ventilation Patient-Focused Outcomes Patients Phase Process Property Pulmonary Edema Pulmonary Gas Exchange Pulmonary Vascular Resistance Recycling Respiratory Failure Risk Safety Science Small Business Innovation Research Grant Stroke Structure of parenchyma of lung Surface System Technology Testing Thrombosis Tidal Volume Time Tissues Trauma Ventilator Ventilator-induced lung injury aerosolized airway epithelium base biomaterial compatibility cost cytokine cytotoxic cytotoxicity design efficacy evaluation high risk improved in vivo in vivo evaluation inflammatory marker lung injury lung volume mechanical force mortality porcine model pressure prototype pulmonary function respiratory response stroke risk tertiary care vapor ventilation

项目摘要

PROJECT SUMMARY Mechanical ventilation (MV) is used in an ICU setting when respiratory failure occurs for a variety of reasons, including acute respiratory distress syndrome (ARDS). The mortality of severe ARDS approaches 50% and even those that survive typically require MV and suffer long-term adverse impacts on their lung function. The aggressive ventilator settings used during MC apply strong mechanical forces during ventilation that can lead to ventilator-induced lung injury (VILI) via physical disruption of the tissues and cells and activation of cytotoxic and inflammatory responses. Alternatives to MV, such as ECMO (extracorporeal membrane oxygenation), can efficiently perform ventilation and oxygenation, is exorbitantly expensive, requires highly specialized teams and equipment that is not widely available, and carries high risks of stroke, bleeding, and thrombosis. We propose that aerosolizing liquid perfluorocarbons (LPs) with the inspired air during MV will achieve more rapid cooling and efficient gas exchange, negating the need for high ventilator settings and thus reducing VILI. To achieve this, Boundless Science is developing a bi-liquid aerosolized therapy (BAT) coupled to a mechanical ventilator to yield a BAT system (BATS) to introduce a fine perfluorocarbon mist that simultaneously cools the lungs to reduce inflammation while enhancing oxygen delivery to overcome pulmonary dysfunction. Our preliminary results indicate that BATS successfully and rapidly cooled isolated pig lungs to 32˚C. We hypothesize that BATS will achieve low polydispersity of median aerosol droplet to obtain uniform pulmonary distribution and consistent efficacy while using an LP mixture that enhances CO2 exhalation and thus improve patient outcomes. At the same time, the evaporative cooling in the epithelium will further reduce inflammation beyond the inherent anti-inflammatory properties of the LPs, while LP recycling within a standard ventilator will reducing costs and making it commercially viable for the first time. The objective of this proposal is to provide proof of concept that BAT coupled with MV will increase pulmonary oxygenation (PaO2/FiO2) by 50% without causing trauma. We will progress toward this objective using the following Specific Aims. Aim 1) Determine the optimal mixture of LPs that has low level cytotoxicity and provides the highest anti-inflammatory effects in vitro. Aim 2) Create the optimal droplet size and LP ratio to effectively infiltrate and cool alveoli with aerosolized LP. Aim 3) Evaluate the optimized aerosolized LP mixture and droplet size from Aims 1 and 2 in an in vivo porcine model of ARDS. Successful results will not only show the potential of BATS but will importantly provide the necessary design guidelines to drive the development of a clinically and commercially viable system.

项目概要当因各种原因发生呼吸衰竭时，在 ICU 环境中使用机械通气 (MV)，包括急性呼吸窘迫综合征 (ARDS)，严重 ARDS 的死亡率接近 50%，即使是那些幸存下来的人通常也需要 MV 并遭受对其肺功能的长期不利影响。 MC 期间使用的激进呼吸机设置会在通气过程中施加强大的机械力，从而导致通过组织和细胞的物理破坏以及细胞毒性的激活来预防呼吸机引起的肺损伤（VILI） MV 的替代方案，例如 ECMO（体外膜肺氧合），可以有效地进行通气和氧合，成本高昂，需要高度专业化的团队和设备尚未广泛普及，并且存在中风、出血和血栓形成的高风险。我们建议在 MV 期间用吸入的空气雾化液体全氟化碳 (LP) 将实现更多效果快速冷却和高效气体交换，无需较高的呼吸机设置，从而减少 VILI。为了实现这一目标，Boundless Science 正在开发一种与机械通风机产生 BAT 系统 (BATS)，引入细小的全氟化碳雾，同时冷却肺部以减少炎症，同时增强氧气输送以克服我们的初步结果表明 BATS 成功且快速地冷却了离体猪。我们发现 BATS 将实现中值气溶胶液滴的低多分散性，以获得使用增强 CO2 呼出的 LP 混合物时，肺部分布均匀，功效一致同时，上皮的蒸发冷却将进一步改善。减少炎症超出 LP 固有的抗炎特性，同时 LP 在标准呼吸机将降低成本并首次使其具有商业可行性。该提案的目的是提供概念证明，即 BAT 与 MV 结合将增加肺功能氧合 (PaO2/FiO2) 提高 50%，且不会造成创伤我们将利用以下方法来实现这一目标。具体目标 1) 确定具有低水平细胞毒性和的最佳 LP 混合物。提供最高的体外抗炎作用目标 2) 创建最佳的液滴尺寸和 LP 比例。用雾化LP有效渗透和冷却肺泡目标3) 评估优化的雾化LP混合物。以及目标 1 和 2 在 ARDS 猪体内模型中的液滴大小成功的结果不仅会显示。 BATS 的潜力，但重要的是提供必要的设计指南来推动开发临床和商业上可行的系统。