COPD Exacerbations: Pharmacogenetic Approaches to Thera*

描述（由申请人提供）：“COPD恶化：药物遗传学治疗方法”提案提出了哈佛医学院一组长期对COPD感兴趣的临床研究人员的承诺，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，制定和实施旨在改善COPD患者护理的协议。申请人建议从住院治疗COPD的患者、主要教学医院已建立的肺病实践以及相关的大型卫生保健提供者网络中招募COPD患者。招募策略包括使用几个已确定COPD患者的大型临床数据库。该提案的科学重点是预防和治疗病情恶化。慢性阻塞性肺病的恶化，定义为呼吸短促的增加和痰量和/或脓量的增加，是患者生活质量的主要决定因素，也是大量卫生保健支出的原因。申请人提出2个协议供网络考虑；一种是通过吸入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加重。第一种方案的潜在优势在于，与目前口服或静脉注射皮质类固醇的标准治疗相比，它的并发症更少。患者将随机分为吸入或口服类固醇治疗加重。

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.