COPD Exacerbations: Pharmacogenetic Approaches to Therapy

描述（由申请方提供）：提案“COPD急性加重：药物遗传学治疗方法”提出了哈佛医学院的一组长期对COPD感兴趣的临床研究者的承诺，他们将作为临床中心参与拟议的COPD临床研究网络，并与其他临床中心合作，创建和实施旨在改善COPD患者护理的方案。申请人建议从住院治疗COPD的患者中招募COPD患者，在主要教学医院建立肺部实践，并建立相关的大型医疗保健提供者网络。招募策略包括使用已确定COPD患者的几个大型临床数据库。该提案的科学重点是预防和治疗急性加重。COPD急性加重（定义为呼吸急促增加和痰量和/或脓性痰增多）是患者生活质量的主要决定因素，并导致大量医疗保健支出。申请人提出了2种方案供网络考虑;一种是针对使用吸入性皮质类固醇治疗急性加重，另一种是通过使用白三烯抑制剂预防急性加重。第一个方案提供了一种治疗的潜在优势，这种治疗比目前口服或静脉注射皮质类固醇的标准治疗并发症更少。患者将随机接受吸入或口服类固醇治疗急性加重。 主要结局为至下次加重的时间。第二部分研究了一类药物白三烯抑制剂的作用，这类药物已被证明对哮喘有益，但尚未在COPD患者中进行系统评价。患者将随机接受齐留通或安慰剂治疗12个月。急性加重的频率将是主要结局。这两种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药物有反应的患者子集。这些分析旨在为COPD患者的异质性人群（估计美国约有1800万人）提供更特异性的治疗靶向策略。

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.