Washington University AsthmaNet

华盛顿大学哮喘网

• 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
• 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

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）：哮喘在美国和世界范围内仍然是一个重要的公共卫生问题，大约6.7%的成年人和8.5%的18岁以下儿童患有哮喘。尽管对哮喘发病机制和治疗策略的理解取得了重大进展，但与哮喘相关的发病率仍在继续。在过去的15年里，美国国立卫生研究院支持的哮喘网络，ACRN和CARE，已经增加了哮喘诊断和治疗的证据基础，这些证据已经显著地纳入了国家和国际哮喘管理指南。尽管知识基础不断增长，但在哮喘护理方面仍有许多未解决的问题，从基于个体患者特征的优化护理策略（个性化医疗）到检查改善哮喘控制的新治疗方法。该提案包含针对三种不同且未充分研究的哮喘人群的临床试验：患有轻度至中度持续性症状哮喘的学龄前儿童，使用低剂量吸入皮质类固醇（ICS）无法充分控制哮喘的青少年和成人，以及尽管使用最大标准治疗仍未控制的严重持续性哮喘的成人。我们将研究患有轻中度哮喘的学龄前儿童的两种治疗策略，以及是否结合生物标志物（呼出一氧化氮的分数浓度）可以预测更有效的治疗策略。我们还建议对哮喘控制不佳和维生素D不足的成人受试者在ICS中添加高剂量维生素D，以评估维生素D是否能改善皮质类固醇反应性，并提供比ICS剂量加倍或与添加长效p激动剂相似的哮喘控制。根据这项研究，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，考虑到与严重哮喘相关的发病率和对当前治疗无效，我们建议进行一项试验，检查一种新型免疫调节剂abatacept的安全性和有效性，它可以抑制t细胞激活所需的共刺激信号（通过CD28）的传递，用于严重持续性不受控制的哮喘受试者。总之，这些研究解决了目前哮喘治疗决策证据基础上的空白，并为哮喘控制不足仍然普遍存在的患者探索了新的治疗策略。