Chicago Metropolitan Asthma Consortium for severe / exacerbation-prone asthma

芝加哥大都会哮喘联盟治疗严重/易加重哮喘

• 批准号: 10219341
• 负责人: Sharon R. Rosenberg
• 金额: $ 42.67万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-23 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219341
• 关键词: Academic Medical Centers; Adolescent; Adult; Advertising; Affect; Age; Ambulatory Care Facilities; American Lung Association; Area; Asthma; Biological Markers; Body mass index; Catchment Area; Chicago; Child; Cities; Clinical; Clinical Markers; Clinical Research; Clinical Treatment; Clinical Trials; Clinical Trials Design; Clinical Trials Network; Clinical trial protocol document; Collaborations; Communities; Community Networks; Development; Disease Progression; Emergency Situation; Enrollment; Ensure; Environmental Risk Factor; Epidemiology; Event; FDA approved; Failure; Foundations; Functional disorder; Future; Generations; Genetic; Goals; Heterogeneity; Hospitals; Human Resources; Industry; Inflammation; Inpatients; Institution; Intervention; Knowledge; Leadership; Location; Masks; Mediating; Medical; Minority Groups; Modeling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; Obesity; Participant; Pathogenesis; Patient Recruitments; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Phenotype; Population; Precision therapeutics; Prevalence; Prostaglandins; Protocols documentation; Research; Research Support; Role; Safety; Symptoms; Testing; Therapeutic; Therapeutic Intervention; Thinness; Time; Translational Research; United States; United States National Institutes of Health; Universities; Ursidae Family; Work; adaptive learning; airway inflammation; arm; asthma exacerbation; asthmatic patient; base; clinical center; clinical practice; collaborative trial; cost; cytokine; design; disease phenotype; early phase clinical trial; efficacy testing; ethnic diversity; experience; follow-up; inner city; innovation; member; metropolitan; model design; mortality; next generation; novel; patient outreach; patient stratification; pediatric patients; personalized intervention; phenotypic biomarker; precision medicine; predictive marker; prevent; programs; racial diversity; recruit; research study; response; social media; success; targeted treatment; underserved minority; Academic Medical Centers; Adolescent; Adult; Advertising; Affect; Age; Ambulatory Care Facilities; American Lung Association; Area; Asthma; Biological Markers; Body mass index; Catchment Area; Chicago; Child; Cities; Clinical; Clinical Markers; Clinical Research; Clinical Treatment; Clinical Trials; Clinical Trials Design; Clinical Trials Network; Clinical trial protocol document; Collaborations; Communities; Community Networks; Development; Disease Progression; Emergency Situation; Enrollment; Ensure; Environmental Risk Factor; Epidemiology; Event; FDA approved; Failure; Foundations; Functional disorder; Future; Generations; Genetic; Goals; Heterogeneity; Hospitals; Human Resources; Industry; Inflammation; Inpatients; Institution; Intervention; Knowledge; Leadership; Location; Masks; Mediating; Medical; Minority Groups; Modeling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; Obesity; Participant; Pathogenesis; Patient Recruitments; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Phenotype; Population; Precision therapeutics; Prevalence; Prostaglandins; Protocols documentation; Research; Research Support; Role; Safety; Symptoms; Testing; Therapeutic; Therapeutic Intervention; Thinness; Time; Translational Research; United States; United States National Institutes of Health; Universities; Ursidae Family; Work; adaptive learning; airway inflammation; arm; asthma exacerbation; asthmatic patient; base; clinical center; clinical practice; collaborative trial; cost; cytokine; design; disease phenotype; early phase clinical trial; efficacy testing; ethnic diversity; experience; follow-up; inner city; innovation; member; metropolitan; model design; mortality; next generation; novel; patient outreach; patient stratification; pediatric patients; personalized intervention; phenotypic biomarker; precision medicine; predictive marker; prevent; programs; racial diversity; recruit; research study; response; social media; success; targeted treatment; underserved minority

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.

项目摘要 来自芝加哥大都会哮喘联盟（CMAC）的申请是对RFA的响应 标题为“ NHLBI严重和/或恶化哮喘的临床中心 （精确）网络”。芝加哥大都市地区有近1000万居民，他们在种族和伦理上都有 杂乱无章。芝加哥市约占该人口的三分之一，患有哮喘 儿童和成人的透镜率超过10％，并且是哮喘死亡率最高的一部分 美国。严重和/或易于加重（S/EP）哮喘影响超过10％的哮喘患者， 占据很大的发病率和大多数与哮喘相关的成本。虽然取得了重大进展 是为了帮助患者控制哮喘症状，如何使用当前疗法来靶向特定的PHE- 精确的诺斯特并预防疾病进展，以及何时以及如何改变这些疗法 失败，尚不清楚。 CMAC包括学术医学中心合作伙伴：西北大学， 芝加哥大学，卢里儿童医院，拉什大学和约翰·H·斯特罗格医院，以及 社区合作伙伴网络。 CMAC具有独特的资格参加精确网络 并为网络临床试验的开发和成功完成和成功贡献 CEPT/机械研究。我们的关键人员在哮喘临床和翻译方面具有丰富的经验 研究，包括探索其病理生理学，发病机理（遗传和环境因素）的研究， 流行病学和治疗；在各自的关键研究支持和CTSA计划中的领导角色 机构；与哮喘研究的多个机构和网络一起成功合作 程序；进入大型，潜水的哮喘人群；并记录了成功入学的能力 在NIH中，基金会和行业赞助了哮喘研究研究和临床试验。我们提出了一个模型 干预顺序，适应性临床试验方案，具有三种针对性的精确干预措施 通过重复评估生物标志物的指导，以告知初始治疗选择和随后的间隔 时尚。此外，我们的建议利用了最新的自适应临床试验设计，仔细的纵向随访， 并将利用早期合并患者的反应指导靶向治疗 我们的目标干预措施包括三种不同的抗周期因子和前列腺素疗法 Th2高的患者以及三种针对Th2-low，肥胖和瘦患者的疗法。参与 CMAC将加强精确的网络，以便它实现其在早期完全成功的目标 - 阶段临床试验以测试S/EP哮喘患者的有针对性干预措施 促进哮喘表型，预测生物标志物和治疗反应性，并积极地告知临床 在严重哮喘患者治疗中的CAL实践。