Asthma Clinical Research Network

描述(由申请者提供)：这是一个哮喘临床研究网络网站的申请，展示了匹兹堡大学将为ACRN带来的多种优势。哮喘影响着1400多万美国人，对非裔美国人和西班牙裔美国人的影响不成比例。哮喘管理指南强调了吸入性皮质类固醇[ICS]对哮喘的作用，基于大量文献证明，ICS平均而言优于其他选择，包括白三烯调节剂[LTM]。这一建议是基于这样一个概念，即大多数哮喘患者在ICS治疗后将有所改善。然而，ACRN最近的一份出版物(MICE)强烈表明，对ICS的反应既不普遍，也不统一。这项应用的一个主要主题是，可以前瞻性地识别治疗反应的可变性，并用于改善哮喘患者的护理。遗传和代谢因素是临床反应的变异性的基础。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ICS、LTM和茶碱的临床反应。然后，我们可能能够利用这些因素作为哮喘治疗阳性反应的预测因子。另一个关键问题是，LTM、茶碱或更高剂量的ICS是否改善了哮喘的控制，特别是肺功能和恶化的发生率。这个问题将在哮喘辅助治疗评估[ESTA]试验中解决。匹兹堡大学提供现有的生产性基础设施，在哮喘临床试验方面的生产力记录，以及由NIH资助的基础和翻译研究计划。我们有一大批现有的哮喘患者，与UPMC健康计划有联系，可以获得5000多名额外的哮喘患者，并且有招募和保留少数族裔受试者的良好历史。我们提供与(PIT)少数民族健康中心的合作，极其强大的少数民族招募战略，强大的GCRC，世界级的基因表达微阵列分析，一个创新的临床药理学中心，包括一个临床药理学分析设施，以及一个药物基因组学核心实验室。PIT大力支持协作的临床网络研究。DART和ESTA试验的数据可以帮助改善哮喘患者的护理。

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.