Strategies to Prevent COPD Exacerbation

描述(由申请人提供)： 慢性阻塞性肺疾病(COPD)是美国发病率和死亡率的主要原因。慢性支气管炎急性加重(AECB)，定义为呼吸困难、咳嗽、痰容量或痰脓肿的急性恶化，与症状、与健康相关的生活质量和肺功能的显著急性恶化有关。对COPD和AECB的临床研究是迫切需要的。我们建议开发一个临床技能发展核心，在设计、进行和分析以COPD相关主题为重点的临床试验方面对初级研究人员进行严格培训。核心将包括一个由多学科研究人员组成的小组，他们在临床研究设计和实施、炎症和宿主反应、文献的系统分析以及新技术的经济影响研究方面具有专业知识。急性感染是AECB高达70%的发作的基础，而炎症在症状性恶化的发生中起重要作用。感染可能是慢性阻塞性肺疾病呼吸道炎症的重要触发因素。14和15个大环内酯类化合物已被证明具有重要的抗炎作用。这些药物在弥漫性泛细支气管炎和囊性纤维化的治疗中发挥了关键作用，而在支气管扩张和慢性阻塞性肺疾病患者中也显示了初步的阳性结果。肺康复可缓解呼吸困难、疲劳，并增强COPD患者的控制感，尽管最近AECB对患者的影响尚不清楚。在本申请中，我们为COPD的临床研究网络(CRN)提出了两个研究方案：1)一项随机前瞻性试验，比较有频繁加重病史的COPD患者在九个月内长期使用大环内酯类抗生素与常规护理的比较；以及2)一项随机前瞻性试验，比较AECB出院后四周综合肺康复计划与出院后常规护理的比较。此外，我们同意1)与其他临床研究中心合作开发、设计和实施网络范围的协议；2)遵守共同的定义和方法以确保协议的完成；3)遵守研究政策和质量保证措施；4)接受基于每位患者比率和CRN制定和执行的协议数量的奖励；5)将研究数据传输到数据和协调中心；6)报告所有不良事件；以及7)制定和遵守传播和发布结果的共同计划。

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in the United States. Acute exacerbations of chronic bronchitis (AECBs), defined as the acute worsening of breathlessness, cough, sputum volume or sputum purulence, are associated with marked acute deteriorations of symptoms, health related quality of life and pulmonary function. Clinical studies in COPD and AECB are sorely needed. We propose to develop a Clinical Skills Development Core to rigorously train junior investigators in the design, conduct and analysis of clinical trials focused on COPD related topics. The core will include a multidisciplinary group of investigators with expertise in clinical study design and conduct, inflammation and host responses, systematic analysis of the literature and the study of economic implications of new technology. Acute infection underlies up to 70% of episodes of AECB, while inflammation is important in the genesis of symptomatic exacerbations. It is likely that infection is an important trigger of airway inflammation in COPD. The 14 and 15 membered macrolides have been demonstrated to exhibit important, anti-inflammatory effects. These agents have assumed a pivotal role in the treatment of diffuse panbronchiolitis and cystic fibrosis, while preliminary positive results have been demonstrated in patients with bronchiectasis and COPD. Pulmonary rehabilitation relieves dyspnea, fatigue and enhances the COPD patient's sense of control although the impact in patients with a recent AECB remains unclear. In this application we propose two research protocols for a Clinical Research Network (CRN) in COPD: 1) a randomized, prospective trial comparing a macrolide antibiotic administered chronically over a nine month period versus usual care in COPD patients with a history of frequent exacerbations; and 2) a randomized, prospective trial comparing a four week comprehensive pulmonary rehabilitation program after discharge for an AECB compared with discharge followed by usual care. In addition, we agree to 1) cooperate with other clinical research centers in the development, design and implementation of network wide protocols; 2) abide by common definitions and methodology to assure completion of protocols; 3) comply with study policies and quality assurance measures; 4) accept awards based on per-patient rates and the number of protocols developed and carried out by the CRN; 5) transmit study data to the Data and Coordinating Center; 6) report all adverse events; and 7) develop and adhere to common plans for the dissemination and publication of results.