SARP

标准和建议措施

• 批准号: 7608179
• 负责人: Serpil C. Erzurum
• 金额: $ 0.21万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608179
• 关键词: Ammonia; Asthma; Computer Retrieval of Information on Scientific Projects Database; Discipline of Nursing; Environment; Epithelial; Functional disorder; Funding; Glutaminase; Grant; Institution; International; Measures; Morbidity - disease rate; Multicenter Trials; Nitric Oxide; Nitrogen Oxides; Outpatients; Oxidation-Reduction; Patients; Peroxynitrous Acid; Production; Pulmonary function tests; Reaction; Reactive Oxygen Species; Refractory; Regulation; Research; Research Personnel; Resource Sharing; Resources; Role; Source; Superoxide Dismutase; Testing; United States National Institutes of Health; Visit; cytotoxic; injured airway; methacholine; mortality; new technology; programs; skin hypersensitivity

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Severe asthma is poorly understood, is refractory to treatment and causes substantial morbidity and mortality. We have found that the airway redox environment is uniquely abnormal in severe asthma. In this project, we propose to define the role of redox regulation in the pathophysiology of severe asthma. To accomplish this, we will make use of shared resources and patients, new technologies and unique capabilities of investigators at 10 large asthma centers. We propose to test the following hypotheses: 1) Airway epithelial glutaminase activity is decreased in severe asthma, resulting in decreased ammonia production and impaired regulation of airway pH; 2) The airway environment in severe asthma is oxidizing because of loss of superoxide dismutase activity and an increase in the formation of reactive oxygen species; and 3) Organic and inorganic abnormalities in airway redox regulation in severe asthma decrease levels of beneficial nitrogen oxides (nitric oxide and S-Nitrosothiols) and increase cytotoxic NO reaction products (such as nitrous and peroxynitrous acids) that potentiate airway injury. This study is part of a large multicenter trial of severe asthma, the severe asthma research program (SARP). We have made extensive use of the GCRC through nursing out-patient visits, nitric oxide (NO) measures, pulmonary function testing, methacholine testing, skin allergy testing, all performed through GCRC support. The study has an NIH appointed DSMB, and has a steering committee with international membership.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 人们对严重哮喘知之甚少，难以治疗，并且导致很高的发病率和死亡率。 我们发现，严重哮喘患者的气道氧化还原环境异常异常。在这个项目中，我们建议定义氧化还原调节在严重哮喘病理生理学中的作用。 为了实现这一目标，我们将利用 10 个大型哮喘中心的共享资源和患者、新技术和研究人员的独特能力。 我们建议检验以下假设：1）严重哮喘时气道上皮谷氨酰胺酶活性降低，导致氨生成减少和气道pH调节受损； 2) 严重哮喘患者的气道环境因超氧化物歧化酶活性丧失和活性氧形成增加而氧化； 3）严重哮喘气道氧化还原调节的有机和无机异常会降低有益氮氧化物（一氧化氮和S-亚硝基硫醇）的水平，并增加细胞毒性NO反应产物（例如亚硝酸和过氧亚硝酸），从而加剧气道损伤。 这项研究是严重哮喘大型多中心试验——严重哮喘研究计划 (SARP) 的一部分。 我们通过护理门诊、一氧化氮 (NO) 测量、肺功能测试、乙酰甲胆碱测试、皮肤过敏测试等方式广泛利用 GCRC，所有这些都是在 GCRC 支持下进行的。 该研究由 NIH 任命为 DSMB，并设有一个由国际成员组成的指导委员会。