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。它的患病率正在上升，到2020年将成为第三大死亡原因(1)。在英国，有90万人被诊断出患有慢性阻塞性肺疾病，很可能还有更多的人没有得到诊断。慢性阻塞性肺病是患者的负担，是医疗保健服务的巨大消耗，每年的费用估计为4.92亿英镑。S的病情恶化的次数被称为病情恶化，慢性阻塞性肺病的恶化占所有入院病例的15%，可能导致死亡。目前COPD恶化的治疗方法是支持性护理，同时使用抗生素和口服皮质类固醇。临床对治疗的反应差异很大，到目前为止，我们还没有强有力的、经过充分验证的测量来指导COPD恶化的治疗。重要的是，抗生素治疗的广泛使用被认为是导致最近超级细菌增加的主要因素。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会使心脏病和糖尿病复杂化。因此，我们目前无法针对COPD恶化进行靶向治疗，这意味着一些COPD患者得到了不适当的治疗，这将脆弱人群置于危险之中。因此，迫切需要有针对性的抗生素和口服皮质类固醇治疗COPD的恶化。在这项提案中，我们将邀请110名COPD患者参加一项为期一年的研究，在这项研究中，我们将进一步评估已知与感染和炎症密切相关的痰和血液中可测量的介质。这些介体将在患者健康和病情恶化时进行测量。这将为我们提供感兴趣的介质的准确水平，然后可以用来决定我们是否使用抗生素和皮质类固醇治疗患者，或者两者都使用，或者两者都不使用。事实上，我们将在第二个一年的干预研究中使用这些测量来指导治疗，该研究将包括与第一个研究相同的患者。在病情恶化时，一半患者将根据标准护理进行治疗，另一半患者将根据第一项研究得出的测量结果进行指导治疗。我们预计，这将为我们提供一个在COPD患者病情恶化时更有效地治疗患者的机会，减少治疗的总使用量，而不会产生任何有害影响。

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.