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。它的患病率正在上升，到2020年将成为死亡的第三大原因（1）。在英国，有900,000人被诊断出患有COPD，可能会有更多未诊断的人。 COPD是患者的负担，对医疗保健提供的巨大浪费，年度费用估计为4.92亿。患者病情恶化的时代被称为加重和COPD加重，占所有医疗入院的15％，可能导致死亡。当前对COPD加重的治疗方法是支持性护理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，迄今为止，我们还没有针对COPD加重的良好验证测量。重要的是，抗生素疗法的广泛使用被认为是导致？超级细菌近期增加的主要因素吗？ MRSA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加重治疗的治疗意味着某些COPD患者的治疗不当，这使脆弱的人群处于危险之中。因此，需要针对COPD加重的抗生素和口服皮质类固醇治疗的迫切需要。在此提案中，我们将邀请110名COPD患者进入一项1年的研究，在该研究中，我们将进一步评估可以在痰液和血液中测量的介质，这些介体与已经众所周知，这些介体与感染和炎症密切相关。当患者良好时，并且在患者患者的情况恶化时，将测量这些介体。这将为我们提供精确的感兴趣介体水平，然后可以用来确定我们是治疗抗生素，皮质类固醇还是不治疗患者。确实，我们将使用这些测量值在第二次1年干预研究中指导治疗，该研究将包括与第一个研究相同的患者。在恶化下，一半的患者将根据标准护理进行治疗，而另一半将由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，以更有效地治疗COPD患者，而无需任何有害影响而减少治疗的总体使用情况。