Biomarkers to target antibiotic and systemic corticosteroid therapy in COPD exacerbations

慢性阻塞性肺疾病（COPD）是一种常见的慢性肺部疾病。其患病率正在上升，到2020年将成为第三大死亡原因（1）。在英国，有90万人被诊断患有COPD，可能还有更多的人未被诊断出来。COPD是患者的负担，也是医疗保健的巨大消耗，每年的费用估计为4.92亿美元。当病人？慢性阻塞性肺病的病情被称为急性加重，慢性阻塞性肺病急性加重占所有医疗入院的15%，并可能导致死亡。目前COPD急性加重的治疗方法是支持性治疗联合抗生素和口服皮质类固醇。对治疗的临床反应差异很大，到目前为止，我们还没有可靠的、经过充分验证的测量方法来指导COPD急性加重的治疗。重要的是，抗生素治疗的广泛使用被认为是导致最近增加的主要因素。超级细菌？耐甲氧西林金黄色葡萄球菌和艰难梭菌感染以及口服皮质类固醇使心脏病和糖尿病复杂化。因此，我们目前无法针对COPD急性加重进行靶向治疗，这意味着一些COPD患者的治疗不当，这将弱势人群置于风险之中。因此，迫切需要针对COPD急性加重的抗生素和口服皮质类固醇治疗。在本提案中，我们将邀请110名COPD患者参加一项为期1年的研究，在该研究中，我们将进一步评估可在痰液和血液中测量的已知与感染和炎症密切相关的介质。这些介质将在患者状况良好和病情加重时进行测量。这将为我们提供感兴趣的介质的精确水平，然后可以用来决定我们是否用抗生素治疗患者，皮质类固醇，两者兼而有之。事实上，我们将使用这些测量结果指导第二项1年干预研究的治疗，该研究将包括与第一项研究相同的患者。在急性加重时，一半患者将根据标准治疗进行治疗，另一半患者将根据第一项研究的测量结果进行治疗。我们预计，这将为我们提供一个机会，在加重时更有效地治疗COPD患者，减少治疗的总使用量，而不会产生任何不利影响。

Chronic obstructive pulmonary disease (COPD) is a common chronic lung disease. Its prevalence is rising and it will become the third leading cause of death by 2020 (1). In the UK 900,000 people are diagnosed with COPD and it is likely that many more remain undiagnosed. COPD is a burden for sufferers and an enormous drain on health care provision with annual costs estimated at #492 million. The times when a patient?s condition worsens is known as an exacerbation and COPD exacerbations account for 15% of all medical admissions and can lead to death. The current treatment for COPD exacerbations is supportive care together with antibiotics and oral corticosteroids. The clinical response to treatment varies considerably and to date we have no robust well-validated measurements to direct therapy for COPD exacerbations. Importantly, the widespread use of antibiotic therapy is implicated as the major contributing factor leading to the recent increase in the ?Superbugs? MRSA and Clostridium difficile infection and oral corticosteroids complicate heart disease and diabetes. Therefore our current inability to target therapy for COPD exacerbations means that some patients with COPD are inappropriately treated and this places a vulnerable population at risk. Therefore there is a pressing need to target antibiotic and oral corticosteroid therapy for COPD exacerbations. In this proposal we shall invite 110 patients with COPD to enter a 1 year study in which we shall further assess mediators that can be measured in sputum and blood that are already known to closely relate to infections and inflammation. These mediators will be measured when patients are well and when they have an exacerbation. This will provide us with precise levels of the mediators of interest that can then be used to decide whether we treat patients with antibiotics, corticosteroids, both or neither. Indeed we shall use these measurements to direct treatment in a second 1 year intervention study that will include the same patients as for the first study. At exacerbations half of the patients will be treated according to standard care and the other half will have their treatment directed by the measurements derived from the first study. We anticipate that this will provide us with an opportunity to treat patients with COPD at times of exacerbations more effectively with a reduction in the total use of treatment without any detrimental effects.