Arizona/Duke Clinical Center for AsthmaNet

描述（由申请人提供）：杜克大学/亚利桑那大学哮喘治疗中心包括两个临床管理试验方案提案。成人哮喘管理试验将评估tnf - α拮抗剂在改善肥胖受试者哮喘控制中的作用，这些受试者在优化药物治疗和治疗合并症后仍保持控制。该儿科哮喘管理试验将检验以下假设：阿奇霉素（一种巨酶）可用于急性哮喘加重的最初症状，以预防这种加重，以及这种预防效果是否对IL8多态性基因型携带者（IL8/-159 AA）具有特异性，我们已经证明这种基因型与嗜中性粒细胞加重的风险增加有关。我们还提出了两个简短的概念建议：一个是我们将测试肥胖哮喘受试者中类固醇抵抗的存在，另一个是我们将确定myrisolated alanine-rich kinase substrate （MARCKS）相关肽（一种潜在的粘液分泌调节剂）在改善哮喘控制中的作用。最后，我们提出了一个临床研究技能发展核心计划，该计划将利用我们临床研究部门的许多临床、遗传、生物学和培训资源，为肺部和过敏研究员以及其他实习生提供培训机会，以设计和实施网络环境下的临床试验。该提案利用了杜克哮喘中心和亚利桑那呼吸中心在严重成人哮喘和儿童哮喘领域的互补优势。杜克哮喘中心在使用侵入性方法获取气道样本的哮喘细胞和分子生物学方面率先开展了工作，而亚利桑那呼吸中心在哮喘遗传学和药物遗传学方面处于领先地位。这两个小组都广泛参与了以前nhlbi资助的哮喘网络，并且他们可以接触到大量患有各种严重程度哮喘的儿童和成人。这些策略，连同我们在协作环境中有效工作的演示能力，是杜克大学/亚利桑那大学AsthmaNet中心可以为AsthmaNet计划做出的独特贡献。

DESCRIPTION (provided by applicant): Two Clinical management trial protocol proposals are included in The Duke/University of Arizona AsthmaNet Center. The adult asthma management trial will assess the role of TNF-alpha antagonists in improving asthma control in obese subjects who remain on control after optimization of pharmacotherapy and treatment of co-morbidities. The pediatric asthma management trial will test the hypothesis that azithromycin, a macrolyte, can be used at the first symptoms of acute asthma exacerbation to prevent such exacerbations, and if this preventive effect is specific for carriers of a genotype in a polymorphism in IL8 (IL8/-159 AA), which we have shown is associated with increased risk of neutrophilic exacerbations. We also propose two brief concept proposals: one in which we will test for the presence of steroid resistance in obese asthmatic subjects, and a second one in which we will determine the effect of myrisolated alanine-rich kinase substrate (MARCKS)-related peptide, which is a potential regulator of mucus secretion, in improving asthma control. Finally, we propose a clinical research skills development core plan that will use the many clinical, genetic and biological and training resources available in both our clinical research units to provide training opportunities for pulmonary and allergy fellows and other trainees in the design and implementation of clinical trials in a network setting. This proposal is leveraged on the complementary strengths on the Duke Asthma Center and the Arizona Respiratory Center in the areas of severe adult asthma and childhood asthma, respectively. The Duke Asthma Center has pioneered work in the cellular and molecular biology of asthma using invasive methods to obtain airway samples, whereas the Arizona Respiratory Center is a leader in the genetics and pharmacogenetics of asthma. Both teams have extensively participated in previous NHLBI-funded asthma networks, and they have access to large populations of both children and adults with asthma of a wide range of severities. These strategies, together with our demonstrated capacity to work effectively in collaborative environments, are unique contributions that the Duke/University of Arizona AsthmaNet Center can make to the AsthmaNet initiative.