Mechanisms, impact and therapeutic targeting of bacterial colonisation in COPD

COPD 中细菌定植的机制、影响和治疗靶向

• 批准号: G1001372/1
• 负责人: Peter Barnes
• 金额: $ 127.8万
• 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: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1001372%2F1
• 关键词: Mechanisms; impact; therapeutic; targeting; bacterial

Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema and is a very common cause of chronic disability and mortality in the UK. There is an underlying inflammation in the lungs of COPD patients which has so far proved very difficult to treat, so that there is a real need to find more effective treatments in the future. This will depend on better understanding the inflammation that occurs in the lungs of COPD patients, which is usually initiated by cigarette smoking. However, once the disease is established stopping smoking does not clear up the problem so we need to find new and more effective treatments. This grant application brings together some of the key centres for COPD research in the UK to explore a new idea. We know that bacteria (bugs) are present the lungs of COPD patients, unlike the lungs of smokers without COPD and non smokers which are sterile. The presence of these bacteria may drive inflammation, which then results in worsening of the disease and also increases the flare-ups, called exacerbations, which may lead to hospital admission. We believe that this is due to failure to remove bacteria from the lungs and therefore these bacteria grow and cause infections. We have evidence that cells that usually defend the lungs (called macrophages and neutrophils) do not eat up and clear the bacteria as they normally do. In addition, these cells fail to clear all the damaged cells from the lung making the inflammation even worse. We have found that these abnormalities can be explained by abnormal functioning of the macrophages and neutrophils and we have identified some of the mechanisms that have gone wrong. This means that we may be able to find treatments that can restore normal function to these cells so that they can sterilise the lung. This should mean that we can clean up the lung normally, which will lead to a reduction in flare-ups and halting the worsening of the disease. We plan to work closely with several pharmaceutical companies so that we can test any new treatments as soon as possible, so that we may be able to find treatments faster. We hope that this innovative research will therefore lead to new treatment approaches for COPD in the future.

慢性阻塞性肺疾病（COPD）包括慢性支气管炎和肺气肿，是英国慢性残疾和死亡的常见原因。COPD患者的肺部存在潜在的炎症，迄今为止已经证明其非常难以治疗，因此未来真实的需要找到更有效的治疗方法。这将取决于更好地了解COPD患者肺部发生的炎症，这通常是由吸烟引起的。然而，一旦疾病确立，戒烟并不能解决问题，所以我们需要找到新的更有效的治疗方法。这项拨款申请汇集了英国COPD研究的一些关键中心，以探索一个新的想法。我们知道，细菌（虫子）存在于COPD患者的肺部，不像没有COPD的吸烟者和非吸烟者的肺部是无菌的。这些细菌的存在可能会导致炎症，从而导致疾病恶化，并增加了突发事件，称为急性加重，这可能导致住院。我们认为这是由于未能从肺部清除细菌，因此这些细菌生长并引起感染。我们有证据表明，通常保护肺部的细胞（称为巨噬细胞和中性粒细胞）不会像正常情况下那样吞噬和清除细菌。此外，这些细胞无法清除肺部所有受损细胞，使炎症更加严重。我们发现这些异常可以用巨噬细胞和中性粒细胞的异常功能来解释，我们已经确定了一些出错的机制。这意味着我们可能能够找到可以恢复这些细胞正常功能的治疗方法，以便它们可以对肺进行消毒。这应该意味着我们可以正常地清理肺部，这将导致减少突发事件并阻止疾病的恶化。我们计划与几家制药公司密切合作，以便我们能够尽快测试任何新的治疗方法，以便我们能够更快地找到治疗方法。因此，我们希望这项创新研究将在未来为COPD带来新的治疗方法。