Mechanisms, impact and therapeutic targeting of bacterial colonisation in COPD

慢性阻塞性肺疾病(COPD)包括慢性支气管炎和肺气肿，在英国是导致慢性残疾和死亡的非常常见的原因。慢性阻塞性肺病患者的肺部存在潜在的炎症，到目前为止已经被证明非常难以治疗，因此未来确实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，这通常是由吸烟引发的。然而，一旦疾病确定，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一些主要的慢性阻塞性肺病研究中心，以探索一个新的想法。我们知道，COPD患者的肺部存在细菌(细菌)，而不同于没有COPD的吸烟者和不吸烟的人的肺部是无菌的。这些细菌的存在可能会导致炎症，从而导致疾病的恶化，并增加称为恶化的突发事件，这可能会导致住院。我们认为，这是由于未能清除肺部的细菌，因此这些细菌生长并导致感染。我们有证据表明，通常保卫肺部的细胞(称为巨噬细胞和中性粒细胞)并不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中所有受损的细胞，从而使炎症更加严重。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。这意味着我们或许能够找到可以恢复这些细胞正常功能的治疗方法，这样它们就可以对肺部进行消毒。这应该意味着我们可以正常清理肺部，这将减少突发事件，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导致未来COPD的新治疗方法。

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.