Center for Chinese Herbal Therapy (CHT) for Asthma

哮喘是世界范围内的主要公共卫生问题，目前影响着美国1500万人，而且发病率还在不断增加。虽然皮质类固醇广泛用于哮喘治疗，但其副作用是一个值得关注的问题，特别是对儿童。最近的一项NIH城市内哮喘研究发现，持续每日吸入皮质类固醇治疗对肺功能没有长期治疗益处，新的哮喘药物，包括白三烯抑制剂和抗IgE，仅显示出边际效益。对这种疾病的安全和有效治疗的需求是迫切的。我们以前曾报道过一种具有免疫调节活性的14味中药配方完全消除了哮喘小鼠模型的气道高反应性。该配方抑制Th 2淋巴细胞分泌的促过敏性炎症介质，而不引起皮质类固醇产生的总体免疫抑制。我们现在已经开发了一个同样有效的公式-ASHMI-，其中只包含三个 草药我们建立了该配方的HPLC指纹图谱用于质量控制。我们建议在三个高度互动的项目中使用ASHMI，其总体目标是评估中草药治疗过敏性哮喘的潜在用途。项目#1将重点研究使用慢性哮喘小鼠模型、离体气管环段和体外Th 2记忆淋巴细胞研究ASHMI治疗作用的药理学作用和免疫学机制。项目#2将评估ASHMI治疗对患有中度至重度持续性哮喘的特应性患者的影响。项目#3将研究三种草药成分之间以及每种草药成分之间可能的协同作用或增强作用，以确定配方中哪些成分最有可能导致ASHMI的各种生物效应，以化学表征这些成分，并表征小鼠中ASHMI相关生物活性成分的药代动力学。这些高度相互依赖的项目将由一个行政核心设施提供支持。拟议项目的互动性质以及项目领导人与其实验室之间的密切合作为集中机构力量开发这种常见疾病的疗法提供了独特的机会。该中心资助的每个项目的综合研究结果将为ASHMI治疗哮喘的有效性和安全性提供实验和临床基础，并最终导致哮喘的新疗法，以及推进我们对ASHMI治疗过敏性哮喘的药理学，免疫学和分子机制的理解。

Asthma is a worldwide major public health problem, which currently affects 15 million people in the United States and the incidence is increasing. Although corticosteroids are widely used for asthma treatment, their side effects are a significant concern, particularly for children. A recent NIH Inner-city Asthma Study found that continuous daily treatment with inhaled corticosteroids had no long-term therapeutic benefit in terms of lung function, and new asthma medications, including leukotriene inhibitors and anti-lgE, have shown only marginal benefits. The need for safe and effective treatments of this disease is urgent. We previously reported that a 14 herb Chinese medicine formula, with immunomodulatory activity completely abrogated airway hyperreactivity in a murine model of asthma. This formula suppressed pro allergic inflammatory mediators secreted by Th2 lymphocytes without causing the overall immunbsupression produced by corticosteroids. We have now developed an equally effective formula-ASHMI-, which contains only three herbs. We have established HPLC fingerprints of this formula for quality control purposes. We propose to use ASHMI in three highly interactive projects whose over all goal is to assess the potential use of Chinese herbal therapy for allergic asthma. Project #1 will focus on investigating the pharmacological effects and immunotherapeutic mechanisms underlying the therapeutic effect of ASHMI using a murine model of chronic asthma, ex vivo tracheal ring segments, and in vitro Th2 memory lymphocytes. Project #2 will assess the effect of ASHMI treatment on atopic patients with moderate to severe persistent asthma. Project #3 will investigate possible synergy or potentiation both between the three herbal components, and between the constituents of each individual herb, to determine which constituents of the formula are most likely responsible for ASHMI's various biological effects, to chemically characterize these constituents, and to characterize, in mice, the pharmacokinetics of relevant biologically active constituents of ASHMI. These highly interdependent programs will be supported by an administrative core facility. The interactive nature of the projects proposed and the close collaboration between project leaders and their laboratories provide a unique opportunity to focus institutional strengths on developing therapies for this common disease. The integrated findings of each project of this center grant will provide experimental and clinical bases regarding the efficacy and safety of ASHMI for asthma treatment and may ultimately lead to a novel therapy for asthma, as well as advance our understanding of the pharmacological, immunological and molecular mechanisms underlying the therapeutic effects of ASHMI on allergic asthma.