ACE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。ACE是一项随机、前瞻性、平行分组试验，涉及500名患有持续性哮喘的市中心参与者，年龄在12-20岁之间。所有参与者每次就诊时都要测量肺活量、ENO和呼出的呼吸冷凝物。第一次访问时将采集血液样本，进行总IgE和特异性IgE、血清嗜酸性粒细胞和可选的遗传学研究。所有参与者都将接受皮肤点刺试验，以确定对室内和室外空气过敏原的敏感性。对常见室内过敏原的暴露将通过对家访期间收集的粉尘进行分析来评估。此外，所有登记的参与者将接受以诊所为基础的专科哮喘护理、遵守评估和遵守教育。这项研究将包括筛查访问(访问1)后的3周磨合期和随机化访问(访问2)后46周的治疗期，在此期间，参与者被安排在参考战略小组或生物标记战略小组。这两个治疗策略组的参与者都将得到与NAEPP指南一致的β-激动剂和/或短期强的松哮喘缓解的救援算法的支持和管理。主要目的评估与不使用特定生物标记物的基于指南的方法相比，补充生物标记物的哮喘治疗方法是否能改善哮喘结果(哮喘症状天数和哮喘加重)。在该方案中评估的生物标记物将是呼出的一氧化氮(ENO)。次要目标1.评估临床评估的哮喘控制改善是否与呼出的一氧化氮(ENO)正常化有关。2.确定敏感度和暴露于市内常见变应原是否会降低ENO改善哮喘控制的有效性。3.确定对这两种哮喘治疗方法的反应差，尽管依从性良好，但是否与推测与哮喘有关的基因或对哮喘药物的反应的特定多态性有关。4.确定eNO是否是吸入性皮质类固醇依从性的敏感指标。5.评估通过临床和肺功能参数评估的哮喘控制改善是否与呼气冷凝液炎症、氧化应激和嗜酸性粒细胞活性的正常化有关。6.确定eNO是否与EBC的炎症、氧化应激和嗜酸性粒细胞活性相关。7.通过临床和肺功能参数评估ENO持续低的患者是否反应差，其特征是EBC测量中性粒细胞活性升高，酸度/氧化应激/炎症持续增加，以及组织修复标志物失衡。8.通过临床和肺功能参数评估ENO持续升高的良好应答者，其特征是EBC测量酸度降低、氧化应激降低、炎症减轻和嗜酸性粒细胞活性降低。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ACE is a randomized, prospective, parallel group trial involving 500 inner city participants, 12-20 years of age, with persistent asthma. Spirometry, eNO, and exhaled breath condensates will be measured at each visit on all participants. Blood samples will be collected at Visit 1 for total and specific IgE, serum eosinophils and optional genetic studies. all participants will undergo skin prick testing to determine sensitivity to both indoor and outdoor aeroallergens. Exposures to common indoor allergens will be assessed via assays of dust collected during a home visit. In addition, all enrolled participants will receive clinic-based specialty asthma care, adherence assessment and adherence education. Tha study will consis of a 3-week run-in period following the Screening Visit (Visit 1) and a 46-week treatment period following the Randomization Visit (Visit 2) in which participants are placed either in the Reference Strategy Group or the Biomarker Strategy Group. Participants in both treatment strategy groups will be supported and managed with rescue algorithms of beta-agonists, and/or short courses of prednisone for asthma exacerabation in a manner consistent with the NAEPP guidelines. Primary Objective To evaluate if the biomarker-supplemented approach to asthma therapy improves asthma outcomes (asthma symptom days and asthma exacerbations) as compared to a guidelines-based approach without the use of a specific biomarker. The biomarker to be evaluated in this protocol will be exhaled nitric oxide (eNO). Secondary Objective 1. To evaluate if improved asthma control as assessed by clinical an lung function parameters will be associated with normalization of exhaled nitric oxide (eNO). 2. To determine if sensitivity and exposure to common inner-city allergens will reduce the effectiveness of eNO to improve asthma control. 3. To determine if a poor response to both approaches of asthma management, despite good adherence, is associated with specific polymorphisms of genes putatively related to asthma or to response to asthma medications. 4. To determine if eNO will be a sensitive indicator of adherence with inhaled corticosteroids. 5. To evaluate if improved asthma control as assessed by clinical and lung function parameters will be associated with normalization of exhaled breath condensate measures of inflammation, oxidative stress, and eosinophil activity. 6. To determine if eNO will correlate wil EBC measures of inflammation, oxidative stress, and eosinophil activity. 7. To evaluate if poor responders as assessed by clinical and lung function parameters who have a persistently low eNO will be characterized by EBC measures of increased neutrophil activity, persistently increased acidity/oxidative stress/inflammation, and imbalanced tissue repair markers. 8. To evaluate if good responders as assessed by clinical and lung function parameters who have a persistently high eNO, will be characterized by EBC measures of reduced acidity, reduced oxidative stress, reduced inflammation, and reduced eosinophil activity.