Asthma Clinical Research Network (ACRN)

描述（申请人提供）：本申请是针对NHLBI RFA HL-02-029（哮喘临床研究网络（ACRN））提交的，拟使用维克森林大学（WFU）肺部和重症监护医学部克洛弗代尔肺部临床研究中心的临床、基因组、流行病学和基础科学资源的独特组合，人类基因组学中心和公共卫生科学部，支持哮喘临床研究网络的临床站点。 我们提出了两套通用的具体目标，其中第一套描述了两个具体的协议，由ACRN考虑实施，第二个努力增加额外的资源和价值，ACRN在其第二个十年的发展。 通信协定：1.过去的协议（吸入性皮质类固醇/长效β-受体激动剂联合治疗持续性哮喘的患者导向与标准治疗）将检验以下假设：（布地奈德160 μ g/福莫特罗4.5 μ g）将以较低的成本提供改善的哮喘控制，固定剂量联合治疗（布地奈德160 μ g /福莫特罗4.5 μ g，每日两次，每次2喷，沙丁胺醇用作急救药物）。 2)SAFE协议（用抗TNF、抗IgE和白三烯调节剂治疗重度哮喘）将检验以下假设：重度哮喘患者（定义为使用氟替卡松500 μ g/沙美特罗50 μ g治疗有症状的患者）的治疗（Advair（R）500/50）bid，含抗IgE（奥马珠单抗）和/或抗TNF（可溶性TNF受体，依那西普）将提供比白三烯受体拮抗剂治疗更好的哮喘控制（LTRA，孟鲁司特），并且在抗IgE和/或抗TNF组中比在白三烯受体拮抗剂组中更多的患者中允许Advair（R）剂量减少到氟替卡松100 μ g/沙美特罗50 μ g。我们进一步提供WFU资源和专业知识：1）在人类基因组学中心，用于确定患者基因型和单体型，用于遗传流行病学分析和药物遗传学研究，用于DNA分离和储存，用于测序，基因分型和单体型候选基因，以及确定支气管镜检查样本中的基因表达水平; 2）在公共卫生科学部（PHS）确定，以a）协助分析主要收集的数据 ACRN方案回答可用数据集可能提出的“辅助”问题，以及B）在PHS社会科学和公共卫生政策部门调查卫生经济学问题和以患者为中心的结果，特别是满意度和信任度;和3）包含在我们的基础科学实验室中，以开发和验证用于多个临床试验中心。

DESCRIPTION (provided by applicant): This application, submitted in response to NHLBI RFA HL-02-029, the Asthma Clinical Research Network (ACRN), proposes to use the unique combination of clinical, genomic, epidemiological, and basic scientific resources located at Wake Forest University (WFU), in the Division of Pulmonary and Critical Care Medicine, the Cloverdale Pulmonary Clinical Research Center, the Center for Human Genomics, and the Department of Public Health Sciences, in support of a Clinical Site for the Asthma Clinical Research Network. We propose two general sets of Specific Aims, the first of which describes two specific protocols for consideration by the ACRN for implementation, and the second which strives to add additional resources and value as the ACRN evolves during its second decade. Protocols: 1) The PAST Protocol (Patient-Directed versus Standard Therapy with an Inhaled Corticosteroid/Long-Acting Beta-Agonist Combination in Persistent Asthma) will test the hypothesis that patient-directed therapy using patient adjusted doses of an inhaled corticosteroid/long acting beta-agonist combination (budesonide 160 mu g/formoterol 4.5 mu g) will provide improved asthma control at less cost with increased patient satisfaction than standard, fixed-dose combination therapy (2 puffs twice a day of budesonide 160 mu g /formoterol 4.5 mu g with albuterol used as the rescue medication). 2) The SAFE Protocol (Treatment of Severe Asthma with Anti-TNF, Anti-IgE, and a Leukotriene Modifier) will test the hypothesis that treatment of patients with severe asthma, defined as those symptomatic on fluticasone 500 mu g/salmeterol 50 mu g (Advair(R) 500/50) bid, with anti-IgE (omalizumab) and/or an anti-TNF (soluble TNF receptor, etanercept) will provide better asthma control than treatment with a leukotriene receptor antagonist (LTRA, montelukast), and permit Advair(R) dose reduction to fluticasone 100 mu g/salmeterol 50 mu g in more patients in the anti-IgE and/or anti-TNF groups, than in the leuktriene receptor antagonist group. We further offer WFU resources and expertise: 1) in the Center for Human Genomics for the determination of patient genotypes and haplotypes for genetic epidemiological analysis and pharmacogenetic studies, for DNA isolation and storage, for sequencing, genotyping and haplotyping candidate genes, and determination of levels of gene expression in bronchoscopy samples; 2) identified in the Department of Public Health Sciences (PHS) to a) assist in the analysis of data collected in main ACRN protocols to answer "ancillary" questions which could be posed with the available data sets, and b) in the PHS Division of Social Science and Public Health Policy to investigate issues of health economics and patient-centered outcomes, particularly satisfaction and trust; and 3) contained within our basic science laboratories to develop and validate improved non-invasive bio-markers of airway inflammation for use in multi-center clinical trials.