Pleural cavity as a driver of ventilator-induced systemic inflammation

胸膜腔是呼吸机引起的全身炎症的驱动因素

• 批准号: MR/V012207/1
• 负责人: Michael Wilson
• 金额: $ 66.18万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV012207%2F1
• 关键词: Pleural; cavity; driver; ventilator; induced

Mechanical ventilation is a crucial component of modern intensive care units. It allows operations to take place that would otherwise be impossible, and is an absolutely vital intervention for critically ill patients with respiratory failure, who would die without ventilator support. Ventilation is however not harmless, and it is now widely accepted that it can worsen patients' outcomes through a process called 'ventilator-induced lung injury', or VILI. People suffering from Acute Respiratory Distress Syndrome (ARDS), which can be caused by lung infections, sepsis, smoke inhalation and many other things, are at particularly high risk from VILI, although ventilation can cause damage even in people without underlying illness. Over the last 20 years, the only way doctors have found to reduce deaths among ARDS patients, is to reduce VILI. But mortality remains high (>40%) and it is likely that there is no way to ventilate without causing damage. Thus, understanding the mechanisms behind VILI is of crucial importance, especially given the huge numbers of critically ill patients currently being ventilated worldwide.The main problem seems to be that the body mounts an immune response to being ventilated, and the subsequent inflammation can cause damage to the lungs and other organs. To investigate this scientists have spent many years looking at different molecules and biological pathways, both inside the airspaces of the lung (alveoli) and within the blood. But these studies have not led to any treatments that work in patients.In this grant we have proposed an alternative idea, based on exploring the pleural cavity. The pleural cavity is a space between the lungs and the ribcage. It is known that this cavity fills with fluid in many ventilated patients, and that patients with more pleural fluid are sicker, but the reasons are not known. We believe that during VILI the pleural space becomes inflamed, and this then spreads around the rest of the body damaging different organs.We already have evidence to support this idea, but to prove it we will carry out various experiments in animal models (mainly mice) and in isolated cells. These will be designed to identify what types of cells and biological pathways are stimulated in the pleural space during ventilation, and how important this pleural cavity inflammation is by blocking different parts of the pathways we identify. If this hypothesis is correct, it has the potential to completely change the focus of investigations into VILI, and open up new avenues for the treatment of ventilated patients.

机械通气是现代重症监护病房的重要组成部分。它允许进行手术，否则是不可能的，并且是呼吸衰竭危重患者的绝对重要的干预措施，这些患者在没有呼吸机支持的情况下会死亡。然而，通气并不是无害的，现在人们普遍认为，它会通过一种称为“呼吸机诱导的肺损伤”（VILI）的过程使患者的预后恶化。患有急性呼吸窘迫综合征（ARDS）的人，可能由肺部感染，败血症，烟雾吸入和许多其他事情引起，患VILI的风险特别高，尽管即使在没有潜在疾病的人中，通气也会造成损害。在过去的20年里，医生发现减少ARDS患者死亡的唯一方法是减少VILI。但死亡率仍然很高（>40%），而且很可能没有办法在不造成损害的情况下重新部署。因此，了解VILI背后的机制至关重要，特别是考虑到目前全世界有大量危重患者正在接受机械通气，主要问题似乎是身体对机械通气产生免疫反应，随后的炎症可能会对肺部和其他器官造成损害。为了研究这个问题，科学家们花了很多年的时间来研究不同的分子和生物途径，包括肺（肺泡）的空气空间和血液中的分子和生物途径。但是这些研究并没有导致任何对患者有效的治疗方法，在这次资助中，我们提出了一个替代的想法，基于对胸膜腔的探索。胸膜腔是肺和胸腔之间的空间。众所周知，在许多通气患者中，该腔充满液体，并且具有更多胸膜液的患者病情更重，但原因尚不清楚。我们认为，在VILI期间，胸膜腔会发炎，然后扩散到身体其他部位，损害不同的器官。我们已经有证据支持这一观点，但为了证明这一点，我们将在动物模型（主要是小鼠）和分离细胞中进行各种实验。这些将被设计用于确定在通气过程中胸膜腔中刺激了哪些类型的细胞和生物通路，以及通过阻断我们确定的通路的不同部分来确定这种胸膜腔炎症的重要性。如果这一假设是正确的，它有可能完全改变VILI的研究重点，并为通气患者的治疗开辟新的途径。

项目成果

Ventilator-Induced Lung Injury Promotes Inflammation Within The Pleural Cavity In A Mouse Model

呼吸机引起的肺损伤会促进小鼠模型胸膜腔内的炎症

• 发表时间: 2023
• 作者: Baldi RF