AsthmaNet: Phenotypic Influences on Asthma Treatments

AsthmaNet：表型对哮喘治疗的影响

基本信息

批准号：
8881266
负责人：
Fernando Holguin
金额：
$ 25.34万
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 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8881266
关键词：
Acute Address Adrenal Cortex Hormones Adult African American Age Agonist Allergic Arachidonate 5-Lipoxygenase Aspirin Asthma Biology Breathing Bronchodilator Agents Caucasians 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 asthmatic 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 AsthmaNet 提案包括 3 个协议，其中第 4 个机制协议是围绕未满足的哮喘需求和表型分析而构建的。这些方案应有助于了解哮喘表型与机制和具体治疗的关系，特别是与健康差异以及种族、社会经济地位（SES）和哮喘严重程度的影响有关。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、心理社会压力和严重哮喘相关）方面固有的专业知识的基础上。我们的提案包括具有少数民族人口外展专业知识的少数族裔健康中心、凯斯西储彩虹婴儿组织的合作伙伴以及匹兹堡阿勒格尼总医院的卫星的参与。第一项临床试验将比较两种已批准的治疗成人哮喘表型的药物，该试验假设 5-脂氧合酶抑制剂比白三烯受体拮抗剂更有效。第二项研究评估了种族与 SES 对儿童皮质类固醇 (CS) 反应的影响，h3TJ0 认为，无论是否考虑 SES，非洲裔美国人的哮喘表型都预示着哮喘儿童对吸入 CS 的反应较差。补充维生素 D 将克服不良反应并改善结果。我们将按种族和社会经济地位分层招募非裔美国人和白人儿童。初步稳定后仍有症状的儿童将接受高剂量 ICS 治疗并确定反应。所有组中未改善的儿童将被随机接受维生素 D 或较高剂量 ICS 治疗，以确定维生素 D + 较低剂量 ICS 是否比较高剂量 ICS 更好或相同程度地改善病情加重和 CS 反应性。机械辅助方案将解决 CS 无反应的各个方面是否可以在体外建模，包括种族/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，严重哮喘治疗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，并将改善其治疗。