Washington University AsthmaNet

华盛顿大学哮喘网

基本信息

批准号：
8301655
负责人：
Leonard B Bacharier
金额：
$ 80.18万
依托单位：
WASHINGTON UNIVERSITY
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/8301655
关键词：
18 year old Accident and Emergency department Acute Address Adolescent Adrenal Cortex Hormones Adult Affect Agonist Allergic Disease American American Lung Association Asthma Biological Markers Book Chapters Breathing Bronchiolitis Budgets CD28 gene Caring Centers for Disease Control and Prevention (U.S.)Cessation of life Characteristics Child Childhood Childhood Asthma Cities Clinical Clinical Research Clinical Trials Clinical Trials Network Critical Care Decision Making Development Diagnosis Disease Dose Double-Blind Method Education Effectiveness Epidemiology Equipment Exhalation Faculty Failure Funding Grant Guidelines Hospitalization Human Hypersensitivity Immunology Individual Inflammatory International Intervention Lead Life Lung Mediating Medicine Morbidity - disease rate National Heart, Lung, and Blood Institute Nitric Oxide Nocturnal Asthma Outcome Pathogenesis Patients Pediatric Hospitals Pediatrics Performance Phase Population Preschool Child Principal Investigator Public Health Pulmonology Recruitment Activity Research Research Personnel Role Safety Severities Sickle Cell Anemia Signal Transduction Site Spirometry T-Cell Activation Therapeutic Translational Research United States United States National Institutes of Health Universities Visit Vitamin D Washington Work airway inflammation base chemokine cohort cytokine disorder prevention effective therapy evidence base human subject improved interest knowledge base medical schools member novel novel therapeutic intervention novel therapeutics professor programs prospective treatment strategy treatment trial

项目摘要

DESCRIPTION (provided by applicant): Asthma remains a substantial public health in the United States and worldwide, with approximately 6.7% of adults and 8.5% of children under 18 years of age affected with asthma. The morbidity associated with asthma continues despite significant advances in the understanding of asthma pathogenesis and treatment strategies. Over the past 15 years, the NIH-supported asthma networks, ACRN and CARE, have added to the evidence base for asthma diagnosis and therapeutics, and this evidence has been prominently incorporated into national and international guidelines for asthma management. Despite this growing knowledge base, there remain numerous unanswered questions in asthma care ranging from strategies to optimize care based upon individual patient characteristics (personalized medicine) to examination of novel therapeutic approaches to improve asthma control. This proposal contains clinical trials directed at three diverse, and understudied asthma populations: preschool children with mild-moderate persistent symptomatic asthma, adolescents and adults with asthma inadequately controlled with low dose inhaled corticosteroids (ICS), and adults with severe persistent asthma which remains uncontrolled despite maximum standard therapy. We will examine two therapeutic strategies for preschool children with mild-moderate asthma and whether the incorporation of a biomarker (fractional concentration of exhaled nitric oxide) allows for prediction of the more effective treatment strategy. We also propose to examine the addition of high dose Vitamin D to ICS in adult subjects with not well-controlled asthma and vitamin D insufficiency to evaluate if the Vitamin D improves corticosteroid responsiveness and provides superior asthma control to doubling the dose of ICS or similar control to the addition of a long-acting p-agonist. In concert with this study, we propose to evaluate the potential mechanisms by which Vitamin D enhances corticosteroid effectiveness. Lastly, given the morbidity associated with severe asthma and failure to respond to current therapy, we propose a trial examining the safety and efficacy of a novel immunomodulatory agent, abatacept, which inhibits the delivery of a co-stimulatory signal (through CD28) required for T-cell activation, in subjects with severe persistent uncontrolled asthma. In summary, these studies address current gaps in the evidence base for asthma treatment decision making as well as explore novel therapeutic strategies in patients in whom inadequate asthma control remains commonplace.

描述（由申请人提供）：哮喘在美国和全球范围内仍然是实质性的公共卫生，大约6.7％的成年人和8.5％的18岁以下儿童患有哮喘。尽管了解哮喘发病机理和治疗策略，但与哮喘相关的发病率仍在继续。在过去的15年中，由NIH支持的哮喘网络ACRN和CARE增加了哮喘诊断和治疗剂的证据基础，并且该证据已被显着纳入国家和国际哮喘管理指南中。尽管知识库不断增长，但在哮喘护理中仍然存在许多未解决的问题，从策略到基于个体患者特征（个性化医学）的策略，再到检查新型治疗方法以改善哮喘控制的方法。该提案包含针对三种多样化且研究研究的哮喘种群的临床试验：患有轻度中度持续性症状性哮喘的学龄前儿童，青少年和哮喘的成年人不充分地控制了低剂量的含皮质类固醇（ICS）的低剂量含量（ICS），以及具有持久性持续性的成年人，但最高且无限制地进行了标准治疗。我们将研究针对患有轻度中度哮喘的学龄前儿童的两种治疗策略，以及生物标志物的掺入（呼出的一氧化氮的分数浓度）是否可以预测更有效的治疗策略。我们还建议在没有很好控制的哮喘和维生素D不足的成年受试者中添加高剂量的维生素D，以评估维生素D是否提高了皮质固醇的反应性，并提供了优质的哮喘控制，以使ICS的剂量增加一倍或将ICS的剂量增加一倍或与长效P-agonist相似。与这项研究的一致性，我们建议评估维生素D增强皮质类固醇有效性的潜在机制。最后，鉴于与严重哮喘和未能应对当前疗法有关的发病率，我们提出了一项试验，检查了一种新型免疫调节剂Abatacept的安全性和功效，该试验抑制了与T-Cell激活所需的共刺激信号（通过CD28）的传递，在具有严重持久无稳定无形的Asthmma的受试者中。总而言之，这些研究涉及哮喘治疗决策的证据基础中的当前差距，并探讨了哮喘控制不足的患者的新型治疗策略仍然很普遍。