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（AECBs）定义为呼吸困难、咳嗽、痰量或痰脓的急性恶化，与症状、健康相关生活质量和肺功能的显著急性恶化相关。COPD和AECB的临床研究是非常必要的。我们建议开发一个临床技能开发核心，以严格培训初级研究人员设计，实施和分析以COPD相关主题为重点的临床试验。核心将包括一个多学科的研究人员小组，他们具有临床研究设计和实施、炎症和宿主反应、文献系统分析和新技术经济影响研究方面的专业知识。急性感染是高达70%的AECB发作的基础，而炎症在症状加重的发生中很重要。感染可能是COPD气道炎症的重要触发因素。14和15元大环内酯类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COPD患者中已证实了初步的阳性结果。肺康复治疗可缓解呼吸困难、疲劳并增强COPD患者的控制感，但对近期发生AECB的患者的影响尚不清楚。在本申请中，我们为COPD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，在有频繁急性加重史的COPD患者中比较长期给予大环内酯类抗生素超过9个月与常规护理;和2）随机化，一项前瞻性试验，比较AECB出院后四周综合肺康复计划与出院后常规护理。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方案; 2）遵守通用定义和方法，以确保完成方案; 3）遵守研究政策和质量保证措施; 4）接受基于每位患者的比率以及CRN开发和执行的方案数量的奖励; 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）制定并遵守结果传播和出版的共同计划。

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.