AsthmaNet: Phenotypic Influences on Asthma Treatments

描述(由申请人提供)：匹兹堡大学的哮喘网络方案包括3个方案，其中第4个方案是围绕未满足的哮喘需求和表型建立的。这些方案应该有助于了解哮喘表型与发病机制和具体治疗的关系，特别是与健康差异和种族、社会经济地位(SES)和哮喘严重程度的关系。这些方案建立在我们在哮喘表型和生物学、种族/民族/社会经济问题、环境影响，特别是与服务不足的人群有关的环境影响、心理社会压力和严重哮喘方面的固有专业知识的基础上。我们的提案包括少数族裔健康中心、凯斯西储彩虹婴儿中心的一名合作伙伴以及匹兹堡阿勒格尼综合医院的一颗卫星。第一项临床试验将比较两种被批准用于治疗成人哮喘表型的药物，该药物假设5-脂氧合酶抑制剂将比白三烯受体拮抗剂更有效。第二项研究评估了种族与SES在儿童皮质类固醇(CS)反应中的作用，h3TJ0认为，非洲裔美国人哮喘的表型，在考虑和不考虑SES的情况下，预测哮喘儿童对吸入CS的不良反应。补充维生素D将克服不良反应，改善结果。我们将招募非裔美国人和高加索儿童，按种族和社会地位分层。初步稳定后仍有症状的儿童将接受大剂量ICS治疗并确定疗效。所有没有改善的组的儿童将随机接受维生素D或更高剂量的ICS治疗，以确定维生素D+低剂量ICS是否比高剂量ICS更好或相同程度地改善恶化和CS反应。机械性辅助方案将解决CS无反应性的一些方面是否可以在体外模拟，包括RACE/SES因素对细胞因子抑制和组蛋白的影响，以及维生素D改善它们的作用。最后，严重哮喘方案将重点关注肥大细胞，特别是前列腺素D2及其与CRTH2的相互作用。我们相信，这些研究解决了哮喘未得到满足的需求，并将改进其治疗方法。

DESCRIPTION (provided by applicant): The University of Pittsburgh AsthmaNet proposal includes 3 protocols, with a 4th mechanistic protocol built around unmet asthma needs and phenotyping. These protocols should contribute to understanding asthma phenotypes in relation to mechanisms and specific treatment, particularly in relation to health disparities and contributions from race, socioeconomic status (SES) and asthma severity. These protocols build on our inherent expertise in asthma phenotyping and biology, racial/ethnic/socioeconomic issues, environmental effects, particularly in relation to underserved populations, psychosocial stress, and severe asthma. Our proposal includes participation from the Center for Minority Health with expertise in outreach in minority populations, a partner at Rainbow Babies of Case Western Reserve and a satellite at Allegheny General Hospital in Pittsburgh. The 1st clinical trial will compare two approved drugs for treatment of the adult onset asthma phenotype, which hypothesizes that a 5-lipoxygenase inhibitor will be more effective than a leukotriene receptor antagonist. The 2nd study evaluates the role of race in relation to SES on corticosteroid (CS) responses in children, h3TJ0thesizing that the African-American asthma phenotype, with and without regard to SES, predicts a poor response to inhaled CSs in asthmatic children. Vitamin D supplementation will overcome the poor response and improve outcomes. We will recruit African American and Caucasian children stratified by race and SES. Children who remain symptomatic following initial stabilization will be treated with high dose ICS and response determined. Children of all groups who do not improve will be randomized to treatment with Vitamin D or higher ICS dose to determine whether Vitamin D + lower dose ICS improves exacerbations and CS responsiveness better or to the same degree than the higher dose ICS. The mechanistic ancillary protocol will address whether aspects of CS unresponsiveness can be modeled in vitro, including effects of race/SES factors on cytokine suppression and histones, and the effect of Vitamin D to improve them. Finally, the severe asthma protocol will focus on the mast cell, specifically prostaglandin D2 and its interaction with CRTH2. We believe these studies address unmet needs in asthma and will improve its therapy.