Chicago Metropolitan Asthma Consortium for severe / exacerbation-prone asthma

项目总结 芝加哥大都会哮喘协会(CMAC)的这项申请是对RFA的回应 题为《NHLBI对严重和/或易加重哮喘的精确干预的临床中心》 (精确)网络“。芝加哥大都市区有近1000万种族和其他种族的居民- 与生俱来的多样性。芝加哥约占总人口的三分之一，该市有哮喘疫情-- 儿童和成人的肺气肿发病率均超过10%，是世界上哮喘死亡率最高的国家之一 美国。重度和/或易加重哮喘(S/EP)影响超过10%的哮喘患者和 这既是相当高的发病率，也是与哮喘相关的大部分成本的原因。在取得实质性进展的同时， 在帮助患者控制哮喘症状方面取得了进展，如何使用现有的治疗方法来针对特定的Phe- 准确和防止疾病进展，以及在发生这种情况时何时和如何改变这些治疗方法 失败的可能性，目前仍不清楚。CMAC包括学术医学中心合作伙伴：西北大学、 芝加哥大学、鲁里儿童医院、拉什大学和约翰·H·斯特罗格医院，以及一名外籍人士- 社区合作伙伴的积极网络。CMAC是唯一有资格参与精密网络的机构 并为网络临床试验的开发和成功完成做出了贡献，并证明了其有效性。 除机械研究外。我们的主要人员在哮喘临床和翻译方面拥有丰富的经验 研究，包括探索其病理生理学、发病机制(遗传和环境因素)、 流行病学和治疗；在各自的关键研究支持和CTSA计划中的领导作用 机构；与多个机构和网络在哮喘研究方面的成功合作 计划；接触到大量的、多样化的哮喘人群；以及有记录的、成功地招募患者的能力 在美国国立卫生研究院，基金会和行业赞助了哮喘研究和临床试验。我们提出了一个模型 干预顺序、适应性临床试验方案，包括三个有针对性的、精确的干预措施 以生物标记物的重复评估为指导，为最初的治疗选择和随后的间期治疗提供信息 发明。此外，我们的建议利用了最新的适应性临床试验设计，仔细的纵向随访， 并将使用早期招募患者的反应来指导随后招募的分成患者的靶向治疗 项目。我们的针对性干预包括三种不同的抗细胞因子和前列腺素疗法 Th2高的患者，以及针对Th2低、肥胖和瘦患者的三种不同的治疗方法。参赛者 CMAC将加强精密网络，以实现早日成功完成的目标- 在S/EP哮喘患者中测试靶向干预的阶段临床试验，产生新的知识重新 评估哮喘表型、预测性生物标志物和治疗反应性，并为临床提供积极信息 CAL实践在重症哮喘患者治疗中的应用

PROJECT SUMMARY This application from the Chicagoland Metropolitan Asthma Consortium (CMAC) is in response to the RFA entitled “Clinical Centers for the NHLBI's Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network”. The Chicago metropolitan area has almost 10 million inhabitants who are racially and eth- nically diverse. The City of Chicago, which represents about one-third of this population, has an asthma preva- lence rates in both children and adults exceeding 10% and has one of the highest asthma mortality rates in the United States. Severe and/or exacerbation prone (S/EP) asthma affects over 10% of asthmatic patients and accounts for both substantial morbidity and a majority of asthma-related costs. While substantial progress has been made in helping patients control asthma symptoms, how to use current therapies to target specific phe- notypes precisely and prevent disease progression, and when and how to change these therapies in the event of failure, remain unclear. The CMAC includes academic medical center partners: Northwestern University, the University of Chicago, Lurie Children's Hospital, Rush University, and John H. Stroger Hospital, and an expan- sive network of Community Partners. The CMAC is uniquely qualified to participate in the PrecISE Network and contribute to the development and successful completion of the network clinical trials and proof of con- cept/mechanistic studies. Our key personnel have extensive experience in asthma clinical and translational research, including studies exploring its pathophysiology, pathogenesis (genetic and environmental factors), epidemiology and treatment; leadership roles in key research support and CTSA programs at their respective institutions; successful collaborations together and with multiple institutions and networks on asthma research programs; access to a large, diverse asthma population; and documented, successful ability to enroll patients in NIH, foundation and industry sponsored asthma research studies and clinical trials. We propose a model intervention sequential, adaptive clinical trial protocol with three targeted, precise interventions that will be guided by repeated assessment of biomarkers to inform both the initial therapy choice and subsequent inter- ventions. Further, our proposal utilizes the latest adaptive clinical trial design, careful longitudinal follow-up, and will use the responses of early-recruited patients to guide targeted therapy in subsequently-enrolled sub- jects. Our targeted interventions include three different anti-cytokine and prostaglandin therapies directed to Th2-high patients, and three different therapies directed to Th2-low, obese and lean patients. Participation by the CMAC will strengthen the PrecISE Network so that it will achieve its goal to complete successfully early- phase clinical trials to test targeted interventions in patients with S/EP asthma, generate new knowledge re- garding asthma phenotypes, predictive biomarkers and therapeutic responsiveness, and positively inform clini- cal practice in the treatment of patients with severe asthma.