AsthmaNet: Phenotypic Influences on Asthma Treatments

AsthmaNet：表型对哮喘治疗的影响

基本信息

批准号：
8301659
负责人：
Fernando Holguin
金额：
$ 85.25万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8301659
关键词：
Acute Address Adrenal Cortex Hormones Adult African American Age Agonist Allergic Arachidonate 5-Lipoxygenase Aspirin Asthma Biology Breathing Bronchodilator Agents Caucasians Caucasoid Race Child Childhood Clinical Clinical Trials Cytokine Suppression Disease Dose Double-Blind Method Eicosanoids Enzymes General Hospitals Genetic Histones Hypersensitivity Incidence Inflammation Inflammation Mediators Inflammatory Leukotriene Antagonists Leukotriene B4 Leukotriene E4 Leukotrienes Lipoxygenase Inhibitors Liver Function Tests Measures Minority Occupational Exposure Onset of illness Outcome Parents Pathway interactions Patients Pattern Pharmaceutical Preparations Phase Phenotype Population Prostaglandin D2 Protocols documentation Psychosocial Stress Quality of life Questionnaires Race Randomized Recruitment Activity Research Personnel Role Running Safety Severities Socioeconomic Status Sputum Supplementation Time Underserved Population Universities Upper Respiratory Infections Vitamin D Work Zileuton chronic rhinosinusitis clinical efficacy comparative comparative efficacy design eosinophil health disparity improved in vitro Model mast cell minority health montelukast neutrophil outreach primary outcome programs racial and ethnic receptor response response marker secondary outcome socioeconomics

项目摘要

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.

描述（由申请人提供）：匹兹堡大学哮喘组织提案包括3个方案，其中围绕未满足的哮喘需求和表型制定了第四个机械方案。这些方案应有助于了解与机制和特定治疗有关的哮喘表型，尤其是与种族，社会经济状况（SES）和哮喘严重程度的健康差异和贡献有关的哮喘表型。这些方案基于我们在哮喘表型和生物学，种族/种族/社会经济问题，环境影响，特别是在服务不足的人群，社会心理压力和严重的哮喘方面的固有专业知识。我们的建议包括来自少数民族健康中心的参与，并在少数民族人口的外展，凯斯·西方储备的彩虹婴儿的合作伙伴和匹兹堡Allegheny综合医院的卫星中参与。第一次临床试验将比较两种批准的药物来治疗成人哮喘表型，该药物假设5-脂氧合酶抑制剂将比白细胞受体拮抗剂更有效。第二项研究评估了种族与SES在儿童中皮质类固醇（CS）反应中的作用，H3TJ0THES，表明非洲裔美国人哮喘表型，无论有没有考虑SES，都预测了对哮喘儿童对吸入CSS的不良反应。补充维生素D将克服不良反应并改善预后。我们将招募按种族和SES分层的非裔美国人和高加索儿童。在初始稳定后保持症状的儿童将通过高剂量IC进行治疗，并确定反应。所有不改善的群体的儿童将被随机地用维生素D或更高的ICS剂量治疗，以确定维生素D +较低剂量ICS是否可以改善加重和CS的反应性或比较高剂量ICS更好或相同的程度。机械辅助方案将解决CS无反应性的方面是否可以在体外进行建模，包括种族/SES因子对细胞因子抑制和组蛋白的影响，以及维生素D对改善它们的影响。最后，严重的哮喘方案将集中在肥大细胞上，特别是前列腺素D2及其与CRTH2的相互作用。我们认为这些研究满足了哮喘中未满足的需求，并将改善其治疗。