Translational Research Center for CAM Therapy of Asthma

哮喘 CAM 治疗转化研究中心

• 批准号: 7091526
• 负责人: David B. Peden
• 金额: $ 117.18万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7091526
• 关键词: alternative medicine; antioxidants; asthma; clinical research; respiratory disease /disorder therapy

The objective of this Translational Research Center for CAM therapy of Asthma is to identify antioxidant Complementary and Alternative Medicine therapies for application in asthma. To achieve this objective, we have assembled a team of investigators uniquely qualified for their roles in this project. Project 1 (Phase I Clinical Screening of CAM therapies for asthma, Drs. Peden, PPG PI, Alexis, Bromberg & Patel, UNC) will screen the effect of CAMs initially identified by Drs. Jiang and Ames (gamma tocopherol) or newly identified by Projects 2 & 3 in allergic asthmatic volunteers for Phase I proof of concept studies to determine in CAM therapies protect against endotoxin, O3, and allergen induced airway inflammation. Project 2 of the PPG (Preclinical evaluation of CAM therapies for asthma, Drs. Wagner & Harkema, MSU) will evaluate anti-inflammatory CAMs (or CAMs + traditional therpies) identified by Project 3 in allergen sensitized rodents determining if these CAMs, alone and in combination with traditional asthma therapies, blunt exacerbation of airway inflammation due to allergen, endotoxin and ozone (commonly encountered causes of asthma exacerbation). They will also carry out classic animal pathology and pharmacokinetic studies of CAMs. Project 3 of the PPG (Mechanistic Discovery of CAM Therapies for Asthma, Drs. Jiang, Illek and Ames at CHORI), will employ molecular and cellular techniques to examine the actions of tocopherols, ascorbate, polyphenols (genistein and resveratrol) on generation of oxygen radicals by MPO and EPO, mediator production via cyclo-oxygenase and lipoxygenase, and cellular activation via MAP kinases and NF-kB, and impact on epithelial cell physiology. A Biochemistry Core (Dr. Ames, core leader) will assess samples for products of tocopherol oxidation and oxidative burst and a Biomarker and Sample Repository Core (Dr. Patel, core leader) will provide support for cytokine and mediator assessment of samples and tissues for all projects. These studies will be coordinated via quarterly conference calls and semi-annual meetings of the project and core leaders rotated among the study sites. UNC will maintain a server accessable by all investigators to facilitate data sharing and planning of eventual human volunteer studies. Use of antioxidants is an under-investigated area and it is highly likely that these CAM agents will be effective in prevention of asthma exacerbation mediated by inflammatory processes.

这个CAM哮喘治疗转化研究中心的目标是确定抗氧化剂补充和替代医学疗法在哮喘中的应用。为了实现这一目标，我们组建了一个调查小组，他们在这个项目中的角色是独一无二的。项目1（Phase I Clinical Screening of CAM therapies for asthma，Drs. Peden，PPG PI，Alexis，Bromberg & Patel，Pennsylvania）将筛选由Jiang和艾姆斯博士最初确定的CAM的效果（γ-生育酚）或项目2和3在过敏性哮喘志愿者中新发现的，用于I期概念验证研究，以确定CAM治疗对内毒素、O3的保护作用，和过敏原诱导的气道炎症。PPG项目2 （哮喘CAM疗法的临床前评价，瓦格纳博士和哈克玛，密歇根州立大学）将在过敏原致敏的啮齿动物中评价项目3鉴定的抗炎CAM（或CAM+传统疗法），确定这些CAM单独或与传统哮喘疗法联合是否会使过敏原、内毒素和臭氧（哮喘恶化的常见原因）引起的气道炎症急剧恶化。他们还将进行CAMs的经典动物病理学和药代动力学研究。PPG项目3（Chori的Jiang，Illek和艾姆斯博士发现CAM治疗哮喘的机制）将采用分子和细胞技术来研究生育酚，抗坏血酸，多酚（染料木黄酮和白藜芦醇）对MPO和EPO产生氧自由基，通过环氧合酶和脂氧合酶产生介体，以及通过MAP激酶和NF-κ B激活细胞的作用， 对上皮细胞生理学的影响。生物化学核心（艾姆斯博士，核心负责人）将评估生育酚氧化和氧化爆发产物的样本，生物标志物和样本储存库核心（Patel博士，核心负责人）将为所有项目的样本和组织的细胞因子和介质评估提供支持。这些研究将通过季度电话会议和半年度项目会议进行协调，核心领导人将在研究中心之间轮换。FDA将维护一个所有研究者均可访问的服务器，以促进数据共享和最终人类志愿者研究的规划。抗氧化剂的使用是一个研究不足的领域，这些CAM药物很可能有效预防炎症过程介导的哮喘恶化。