Arizona/Duke Clinical Center for AsthmaNet

描述(由申请人提供)：杜克大学/亚利桑那大学哮喘网络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肿瘤坏死因子-α拮抗剂在改善肥胖受试者哮喘控制方面的作用，这些受试者在优化药物治疗和治疗并存疾病后仍处于控制状态。儿科哮喘治疗试验将测试假设，即大分子阿奇霉素可以在哮喘急性加重的第一个症状时使用以防止这种加剧，以及这种预防效果是否对IL8(IL8/-159 AA)基因多态的携带者具有特异性，我们已经证明这与中性粒细胞恶化的风险增加有关。我们还提出了两个简单的概念建议：一个是我们将测试肥胖哮喘受试者是否存在类固醇抵抗，另一个是我们将确定肉豆蔻酸丙氨酸激酶底物(MARCKS)相关肽在改善哮喘控制方面的效果，MARCKS是一种潜在的粘液分泌调节器。最后，我们提出了一项临床研究技能发展核心计划，该计划将利用我们两个临床研究单位可用的许多临床、遗传和生物以及培训资源，为肺部和过敏研究员以及其他受训人员提供在网络环境下设计和实施临床试验的培训机会。这项建议利用了杜克哮喘中心和亚利桑那州呼吸中心在成人严重哮喘和儿童哮喘领域的互补优势。杜克哮喘中心在哮喘的细胞和分子生物学方面开创了先河，使用侵入性方法获取呼吸道样本，而亚利桑那州呼吸中心在哮喘的遗传学和药物遗传学方面处于领先地位。这两个团队都广泛参与了之前由NHLBI资助的哮喘网络，他们可以接触到患有各种严重程度的哮喘的儿童和成人的大量人口。这些策略，加上我们在协作环境中证明的有效工作能力，是杜克/亚利桑那大学哮喘网络中心可以为哮喘网络倡议做出的独特贡献。

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.