COPD Exacerbations: Pharmacogenetic Approaches to Thera*

描述(由申请人提供)：“慢性阻塞性肺疾病加重：药物遗传学治疗方法”的提案提出了哈佛医学院一组长期关注慢性阻塞性肺病的临床研究人员的承诺，他们将作为临床中心参与拟议的慢性阻塞性肺疾病临床研究网络，并与其他临床中心合作，制定和实施旨在改善慢性阻塞性肺病患者护理的方案。申请者建议从住院治疗COPD的患者中招募COPD患者，主要教学医院的既定肺部实践，以及相关的大型医疗保健提供者网络。招募策略包括使用几个大型临床数据库，这些数据库已经确定了COPD患者。该提案的科学重点是预防和治疗病情恶化。慢性阻塞性肺疾病的恶化是患者生活质量的主要决定因素，占医疗保健支出的很大一部分。慢性阻塞性肺病的加重被定义为呼吸短促的增加和痰的数量和/或脓液的增加。申请人提出了两个方案供该网络审议；一个是针对吸入性皮质类固醇治疗急性加重，第二个是通过使用白三烯抑制剂预防恶化。第一种方案提供的潜在优势是，与目前口服或静脉注射皮质类固醇的标准疗法相比，这种疗法的并发症较少。患者将被随机分为吸入或口服类固醇治疗恶化。 主要结果将是下一次恶化的时间。第二项研究考察了一类药物--白三烯抑制剂的作用，该药物已被证明对哮喘有益，但尚未在COPD患者中进行系统评估。患者将随机接受齐留通或安慰剂治疗12个月。恶化的频率将是主要结果。这两个方案都有相关的药物遗传学研究，旨在确定可能对特定类别的药物有反应的患者亚群。这些分析旨在为在COPD患者的不同人群中进行更具体的针对性治疗提供一种战略，据估计，美国COPD患者约有1800万人。

DESCRIPTION (provided by applicant): The proposal "COPD Exacerbations: Pharmacogenetic Approaches to Therapy" presents the commitment of an established group of clinical investigators at Harvard Medical School with a long-standing interest in COPD to participate as a Clinical Center in the proposed COPD Clinical Research Network and to work with other Clinical Centers to create and implement protocols directed at improving the care of patients with COPD. The applicants propose to recruit patients with COPD from patients admitted to hospitals for treatment of COPD, established pulmonary practices in major teaching hospitals, and an associated large health care provider network. Strategies for recruitment include the use of several large clinical databases that have identified patients with COPD. The scientific focus of the proposal is on the prevention and treatment of exacerbations. Exacerbations of COPD, defined as an increase in shortness of breath and an increase in the amount and/or purulence of sputum, are a major determinant of patient quality of life and account for substantial health care expenditures. The applicants propose 2 protocols for consideration by the network; one is directed at treatment of acute exacerbations with inhaled corticosteroids and the second at prevention of exacerbations by use of a leukotriene inhibitor. The first protocol offers the potential advantage of a therapy that has fewer complications than current standard therapy with oral or intravenous corticosteroids. Patients will be randomized to either inhaled or oral steroids for therapy of exacerbation. The primary outcome will be time to next exacerbation. The second examines the role of a class of medications, leukotriene inhibitors, that has been demonstrated to be beneficial in asthma but have not been systematically evaluated in patients with COPD. Patients will be randomized to receive zileuton or placebo for 12 months. Frequency of exacerbations will be the primary outcome. Both protocols have associated pharmacogenetic studies designed to identify subsets of patients likely to respond to the particular class of medications. These analyses are intended to provide a strategy for more specific targeting of therapy within the heterogeneous population of patients with COPD, estimated at approximately 18 million people in the U.S.