COPD Clinical Research Network

描述（由申请人提供）： 加州大学弗朗西斯科分校肺部和重症监护医学部的研究者在此申请参加合作的COPD临床研究网络，以检查COPD的现有和新疗法和管理策略，并将该网络的发现迅速传播给医学界。 COPD是美国第四大死亡原因，相关的经济和社会负担巨大。 随着COPD病理生物学的新信息和新的治疗方法的出现，需要进行大规模、仔细进行的多中心协作研究，以确定这些新策略在我们治疗方案中的位置。 本申请中包括两个特定的方案;这两个方案都测试了与COPD相关的重要临床问题的新治疗方法。 第一个提案，“TNF-α抑制在COPD中的作用”，检查了针对强效促炎细胞因子TNF-α的单克隆抗体降低中重度COPD患者急性加重率的能力。 急性加重占与COPD相关的急诊科就诊、住院和死亡的大部分。 该提案将检查抗TNF-α治疗对急性加重的影响，以及急性加重、症状、肺功能、生活质量、气道分泌物中的炎症标志物和与粘液产生相关的上皮细胞基因表达之间的关系。 第二个项目“COPD相关肺动脉高压中内皮素-1的抑制”将研究内皮素A和B受体拮抗剂波生坦治疗是否能改善肺动脉高压患者的能力，这些患者的预后很差。 有证据表明，肺动脉病变不仅仅是由于低氧血症，血管扩张剂治疗可能是有益的。 本研究将测试波生坦口服给药治疗和临床重要终点，包括运动能力、功能分级、呼吸困难、生活质量和总体临床状态。

DESCRIPTION (provided by applicant): Investigators in the Division of Pulmonary and Critical Care Medicine at the University of California, San Francisco hereby apply to participate in a cooperative COPD Clinical Research Network, to examine existing and novel therapies and management strategies for COPD, and to rapidly disseminate the findings of this Network to the medical community. COPD is the 4th leading cause of death in the United States, and the associated financial and social burden is enormous. As new information on the pathobiology of COPD and new approaches for management appear, large, carefully conducted, collaborative multicenter studies are required to define the position of these new strategies in our therapeutic algorithm. Two specific protocols are included in this application; both test novel therapeutic approaches to important clinical problems associated with COPD. The first proposal, "The Effects of TNF-alpha Inhibition in COPD", examines the ability of a monoclonal antibody against the potent proinflammatory cytokine TNF-alpha to reduce the rate of exacerbations in patients with moderate-to-severe COPD. Exacerbations account for most of the emergency department visits, hospitalizations, and deaths associated with COPD. This proposal will examine the effect of anti-TNF-alpha therapy on exacerbations, and the relationship between exacerbations, symptoms, lung function, quality of life, markers of inflammation in airway secretions, and expression of epithelial cell genes related to mucus production. The second project, "Inhibition of Endothelin-1 in COPD-related Pulmonary Arterial Hypertension" will examine whether treatment with the Endothelin A and B receptor antagonist bosentan improves capacity in patients with pulmonary arterial hypertension, and the prognosis for these patients is poor. Evidence suggests that the pulmonary artery lesion is not due solely to hypoxemia, and that vasodilator therapy may be beneficial. This study will test an orally-administered therapy with bosentan, and clinically-important endpoints including exercise capacity, functional class, dyspnea, quality of life, and overall clinical status.