Biomarkers to target antibiotic and systemic corticosteroid therapy in COPD exacerbations

COPD 恶化时针对抗生素和全身皮质类固醇治疗的生物标志物

• 批准号: G0601369/1
• 负责人: Christopher Brightling
• 金额: $ 74.38万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601369%2F1
• 关键词: Biomarkers; target; antibiotic; systemic; corticosteroid

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.

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90万人被诊断患有慢性阻塞性肺病，可能还有更多的人未被诊断出来。慢性阻塞性肺病是患者的负担，也是医疗保健服务的巨大消耗，每年的费用估计为4.92亿美元。当一个病人？慢性阻塞性肺病病情恶化被称为急性加重，慢性阻塞性肺病急性加重占所有住院病例的15%，并可导致死亡。目前对慢性阻塞性肺病加重的治疗是支持治疗以及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、经过验证的测量方法来指导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近期病例增加的主要因素。超级细菌吗?MRSA和艰难梭菌感染和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恶化进行靶向治疗，这意味着一些COPD患者治疗不当，这使弱势群体处于危险之中。因此，迫切需要靶向抗生素和口服皮质类固醇治疗COPD恶化。在本提案中，我们将邀请110名COPD患者进入一项为期1年的研究，在该研究中，我们将进一步评估可在痰和血液中测量的介质，这些介质已知与感染和炎症密切相关。这些介质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精确水平，然后可以用来决定我们是用抗生素、皮质类固醇治疗患者，还是两者都用，还是不用。事实上，我们将在第二个为期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。在病情加重时，一半患者将按照标准护理进行治疗，另一半患者将根据第一项研究得出的测量结果进行治疗。我们预计，这将为我们提供一个机会，更有效地治疗COPD患者，减少治疗的总使用量，而不会产生任何有害影响。