Asthma Clinical Research Network

哮喘临床研究网络

• 批准号: 6676764
• 负责人: William J Calhoun
• 金额: $ 80.05万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6676764
• 关键词: antiinflammatory agents; asthma; beta adrenergic agent; bronchodilators; chemokine; clinical research; clinical trials; cooperative study; corticosteroids; drug metabolism; genetic polymorphism; human subject; human therapy evaluation; inhalation drug administration; leukotrienes; patient care management; patient oriented research; pharmacogenetics; respiratory airflow measurement; respiratory disorder chemotherapy; respiratory function; respiratory pharmacology; theophylline; tomography

DESCRIPTION (provided by applicant): This application for an Asthma Clinical Research Network site presents the multitude of strengths which the University of Pittsburgh would bring to the ACRN. Asthma affects more than 14 million Americans, and disproportionately affects African-Americans and Hispanics. Guidelines for asthma management highlight the role of inhaled corticosteroids [ICS] for asthma, based on a large body of literature demonstrating superiority, on average, of ICS over other options, including leukotriene modifiers [LTM]. This recommendation is based on the concept that the majority of asthmatics will improve with ICS. A recent ACRN publication (MICE), however, strongly suggests that response to ICS is neither universal nor uniform. A principal theme of this application is that variability in response to therapy can be identified prospectively, and used to improve the care of patients with asthma. Genetic and metabolic factors underlie variability in clinical response. We propose to measure polymorphisms in genes related to asthma and in drug metabolizing enzymes, to measure functional activity of drug metabolizing enzymes, and to measure clinical response to ICS, LTM, and theophylline in the Determinants in Asthma of Response to Therapy [DART] protocol. We then may be able to use these factors as predictors of positive response to asthma therapy. Another key question is whether LTM, theophylline, or higher dose ICS improve asthma control, especially lung function and rates of exacerbation. This question will be addressed in the Evaluation of Supplemental Therapy for Asthma [ESTA] trial. The University of Pittsburgh offers an existing, productive infrastructure with a track record of productivity in clinical trials in asthma, and an NIH-funded basic and translational research program. We have a large existing cadre of asthma patients, links to the UPMC Health Plan for access to more than 5000 additional asthmatics, and a demonstrated history of recruiting and retaining minority subjects. We offer collaboration with the (Pitt) Center for Minority Health, extremely strong minority recruiting strategies, a strong GCRC, world-class gene expression microarray analysis, an innovative Center for Clinical Pharmacology, including a Clinical Pharmacology Analytic Facility, and a Pharmaco-genomics Core Laboratory. Pitt strongly supports collaborative, clinical network research. Data from the DART and ESTA trials can help to improve the care of patients with asthma.

描述（由申请人提供）：这份哮喘临床研究网络网站申请展示了匹兹堡大学将为 ACRN 带来的众多优势。 哮喘影响着超过 1400 万美国人，其中非洲裔美国人和西班牙裔美国人受到的影响尤为严重。 哮喘管理指南强调了吸入皮质类固醇 [ICS] 对哮喘的作用，该指南基于大量文献，证明 ICS 平均优于其他选择，包括白三烯调节剂 [LTM]。 该建议基于这样的理念：大多数哮喘患者会通过 ICS 得到改善。 然而，最近的 ACRN 出版物 (MICE) 强烈表明，对 ICS 的反应既不普遍也不统一。 该应用的一个主题是可以前瞻性地识别治疗反应的变异性，并用于改善哮喘患者的护理。遗传和代谢因素是临床反应变异的基础。 我们建议测量哮喘相关基因和药物代谢酶的多态性，测量药物代谢酶的功能活性，并测量哮喘治疗反应决定因素 [DART] 方案中对 ICS、LTM 和茶碱的临床反应。 然后我们也许能够使用这些因素作为哮喘治疗积极反应的预测因素。 另一个关键问题是 LTM、茶碱或更高剂量的 ICS 能否改善哮喘控制，尤其是肺功能和恶化率。 这个问题将在哮喘补充治疗评估 [ESTA] 试验中得到解决。 匹兹堡大学提供现有的、富有成效的基础设施，在哮喘临床试验方面拥有良好的生产力记录，以及美国国立卫生研究院 (NIH) 资助的基础和转化研究项目。 我们现有大量哮喘患者，与 UPMC 健康计划有联系，可以接触到 5000 多名额外的哮喘患者，并且有招募和留住少数族裔受试者的良好历史。 我们提供与（皮特）少数民族健康中心的合作、极其强大的少数民族招募策略、强大的 GCRC、世界一流的基因表达微阵列分析、创新的临床药理学中心（包括临床药理学分析设施）和药物基因组学核心实验室。 皮特强烈支持协作临床网络研究。 DART 和 ESTA 试验的数据有助于改善哮喘患者的护理。