COPD Clinical Research Network

描述(由申请人提供)： 加州大学旧金山分校肺科和重症医学部的研究人员特此申请加入合作的COPD临床研究网络，检查现有的和新的COPD治疗方法和管理策略，并将该网络的研究结果迅速传播给医学界。慢性阻塞性肺病是美国第四大死因，相关的经济和社会负担是巨大的。随着有关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、仔细地进行的多中心协作研究来确定这些新策略在我们的治疗算法中的位置。 这项应用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。第一个方案是“肿瘤坏死因子-α抑制在慢性阻塞性肺疾病中的作用”，研究了一种针对强大的促炎细胞因子肿瘤坏死因子-α的单抗降低中到重度慢性阻塞性肺疾病患者病情恶化的能力。与慢性阻塞性肺疾病相关的急诊科就诊、住院和死亡中，病情加重占了大部分。这项建议将研究抗肿瘤坏死因子-α治疗对急性加重的影响，以及恶化、症状、肺功能、生活质量、呼吸道分泌物中的炎症标志物以及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《在COPD相关的肺动脉高压中抑制内皮素-1》将考察内皮素A和B受体拮抗剂波生坦的治疗是否能改善肺动脉高压患者的能力，而这些患者的预后很差。有证据表明，肺动脉损伤不仅仅是由于低氧血症，血管扩张剂治疗可能是有益的。这项研究将测试口服波生坦的治疗，以及临床上重要的终点，包括运动能力、功能等级、呼吸困难、生活质量和总体临床状况。

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.