ACE

高手

• 批准号: 7378673
• 负责人: FLOYD J MALVEAUX
• 金额: $ 12.48万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378673
• 关键词: asthma; biomarker; eosinophil; inflammation; lung; oxidative stress; respiratory function

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。 ACE 是一项随机、前瞻性、平行分组试验，共有 500 名 12-20 岁患有持续性哮喘的市中心参与者参与。每次访视时都会对所有参与者进行肺活量测定、eNO 和呼出气体冷凝物的测量。将在第 1 次就诊时采集血样，用于总 IgE 和特异性 IgE、血清嗜酸性粒细胞和可选的基因研究。所有参与者都将接受皮肤点刺测试，以确定对室内和室外空气过敏原的敏感性。将通过对家访期间收集的灰尘进行分析来评估对常见室内过敏原的暴露情况。此外，所有登记的参与者都将接受基于临床的专业哮喘护理、依从性评估和依从性教育。 这项研究将包括筛选访问（访问 1）后的 3 周磨合期和随机访问（访问 2）后的 46 周治疗期，其中参与者被置于参考策略组或生物标记组中策略组。两个治疗策略组的参与者都将按照 NAEPP 指南的方式接受 β 受体激动剂救援方案和/或短期泼尼松治疗哮喘发作的支持和管理。 主要目的 评估与不使用特定生物标志物的基于指南的方法相比，补充生物标志物的哮喘治疗方法是否可以改善哮喘结局（哮喘症状天数和哮喘恶化）。本协议中要评估的生物标志物是呼出一氧化氮 (eNO)。 次要目标 1. 评估临床肺功能参数评估的哮喘控制改善是否与呼出一氧化氮 (eNO) 正常化相关。 2. 确定敏感性和接触常见的市中心过敏原是否会降低 eNO 改善哮喘控制的有效性。 3. 确定尽管坚持良好，但对两种哮喘治疗方法的不良反应是否与推测与哮喘或哮喘药物反应相关的基因的特定多态性有关。 4. 确定 eNO 是否是吸入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的改善是否与炎症、氧化应激和嗜酸性粒细胞活性的呼出气冷凝物测量值的正常化相关。 6. 确定 eNO 是否与炎症、氧化应激和嗜酸性粒细胞活性的 EBC 测量值相关。 7. 评估通过临床和肺功能参数评估的 eNO 持续较低的反应不佳者是否会通过中性粒细胞活性增加、酸度/氧化应激/炎症持续增加和组织修复标志物不平衡的 EBC 测量来表征。 8. 评估通过临床和肺功能参数评估的具有持续高 eNO 的良好反应者是否会以酸度降低、氧化应激减少、炎症减少和嗜酸性粒细胞活性减少的 EBC 测量为特征。