Developmental Clinical Studies: Does GM-CSF restore effective neutrophil function in critically ill patients?

入住重症监护室（ICU）的患者在医院发生新感染的风险非常高。这些医院感染通常是由对抗生素没有反应的细菌引起的，通常被称为？超级细菌？ICU中发生新感染的患者更有可能死亡，或在ICU中停留更长时间。尽管有各种各样的方法来预防这些医院感染，但它们在ICU中仍然普遍存在，令人无法接受。我们最近发现，主要负责对抗细菌的关键血细胞（称为中性粒细胞）通常无法在ICU患者中有效工作。这似乎有助于增加感染的风险。在实验室中向这些无功能的中性粒细胞添加药物（GM-CSF）总是可以改善其功能。这表明，如果可以识别出中性粒细胞功能低下的高危患者，GM-CSF可能能够预防感染。然而，GM-CSF以前从未专门针对具有无功能中性粒细胞的ICU患者。因此，确定GM-CSF是否可以预防ICU感染的下一个关键步骤是测试GM-CSF是否可以改善高危患者的中性粒细胞功能。因此，我们的目标是使用简单的实验室测试来识别中性粒细胞功能低下的ICU患者。患者将被随机分配接受GM-CSF或模拟药物（安慰剂）。在项目完成之前，患者和医生都不会知道是否给予了GM-CSF或安慰剂，届时研究小组将分析结果。这种类型的研究被称为随机安慰剂对照双盲试验，被广泛认为是发现治疗是否真的有效的最佳方法。通过这种方式，我们将确定GM-CSF是否改善中性粒细胞的功能。如果这？概念验证？这项研究确实证明了GM-CSF的益处，它将迅速为大型研究铺平道路，以确定当专门针对中性粒细胞功能低下的患者时，GM-CSF是否可以预防ICU感染的发展。

Patients admitted to intensive care units (ICUs) are at very high risk of developing new infections in hospital. These hospital infections are commonly caused by bacteria that do not respond to antibiotics and are often termed ?superbugs?. Patients in ICU who develop new infections are more likely to die, or to have longer stays in ICU. Despite a variety of approaches aiming to prevent these hospital infections, they remain unacceptably common in the ICU.We have recently shown that the key blood cells (called neutrophils) mainly responsible for fighting bacteria commonly fail to work efficiently in ICU patients. This seems to contribute to the increased risk of infection. Adding a drug (GM-CSF) to such non-functioning neutrophils in the laboratory invariably improves their function. This suggests that, if high-risk patients with poorly functioning neutrophils could be identified, GM-CSF may be able to prevent infections. However GM-CSF has never been specifically targeted to ICU patients with non-functioning neutrophils before. The next crucial step in establishing whether GM-CSF may prevent infections in ICU is therefore to test whether GM-CSF improves the function of neutrophils in high-risk patients.Our aim is therefore to identify ICU patients who have poorly functioning neutrophils, using a simple laboratory test. The patients will be randomly assigned to receive either GM-CSF or a dummy drug (placebo). Neither the patient nor the doctors will be aware whether GM-CSF or placebo has been given until after the project is completed, when the research team will analyse the results. This type of study is called a randomised placebo controlled double blind trial and is widely accepted to be the best way to find out if a treatment really works or not. In this way we shall establish whether GM-CSF improves the function of neutrophils. If this ?proof of concept? study does demonstrate benefit for GM-CSF, it would rapidly pave the way for large studies establishing if GM-CSF can prevent development of infection in ICU when targeted specifically at patients whose neutrophils function poorly.