Arizona/Duke Clinical Center for AsthmaNet

杜克/亚利桑那大学哮喘网络中心包含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的哮喘控制方面的作用，这些受试者在优化药物治疗和治疗合并症后仍保持控制。儿童哮喘管理试验将检验阿奇霉素（一种大分子电解质）可用于急性哮喘急性加重的最初症状以预防此类急性加重的假设，以及这种预防作用是否对IL 8多态性（IL 8/-159 AA）基因型携带者具有特异性，我们已经证明IL 8多态性与嗜酸性粒细胞性急性加重的风险增加相关。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，第二个是我们将确定富含丙氨酸的激酶底物（MARCKS）相关肽（它是粘液分泌的潜在调节剂）在改善哮喘控制方面的作用。最后，我们提出了一个临床研究技能发展的核心计划，将使用许多临床，遗传和生物学和培训资源，在我们的临床研究单位提供培训机会，为肺和过敏研究员和其他学员在设计和实施临床试验的网络设置。 该提案利用了杜克哮喘中心和亚利桑那呼吸中心分别在严重成人哮喘和儿童哮喘领域的互补优势。杜克哮喘中心率先使用侵入性方法获得气道样本，在哮喘的细胞和分子生物学方面开展工作，而亚利桑那呼吸中心是哮喘遗传学和药物遗传学方面的领导者。这两个团队都广泛参与了以前NHLBI资助的哮喘网络，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，以及我们在协作环境中有效工作的能力，是杜克/亚利桑那大学哮喘网络中心可以为哮喘网络计划做出的独特贡献。

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.