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资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。ACE是一项随机、前瞻性、平行组试验，涉及500名12-20岁患有持续性哮喘的内城参与者。将在每次访视时测量所有受试者的肺功能、eNO和呼出气冷凝物。将在访视1时采集血液样本，用于总IgE和特异性IgE、血清嗜酸性粒细胞和可选的遗传学研究。所有参加者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。将通过对家访期间收集的灰尘进行分析来评估常见室内过敏原的暴露。此外，所有入组的受试者将接受基于诊所的哮喘专科护理、依从性评估和依从性教育。 该研究将包括筛选访视（访视1）后的3周导入期和随机化访视（访视2）后的46周治疗期，其中受试者被置于参考策略组或生物标志物策略组。两个治疗策略组的参与者将以符合NAEPP指南的方式，通过β受体激动剂和/或短期泼尼松治疗哮喘恶化的补救算法得到支持和管理。 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能改善哮喘结局（哮喘症状天数和哮喘急性发作）。本方案中评价的生物标志物为呼出气一氧化氮（eNO）。 次要目标1。评价通过临床肺功能参数评估的哮喘控制改善是否与呼出气一氧化氮（eNO）正常化相关。2.确定敏感性和暴露于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.确定对两种哮喘管理方法的不良反应，尽管依从性良好，是否与哮喘相关基因的特异性多态性或对哮喘药物的反应有关。4.确定eNO是否是吸入性皮质类固醇依从性的敏感指标。5.评价通过临床和肺功能参数评估的哮喘控制改善是否与呼出气冷凝物炎症、氧化应激和嗜酸性粒细胞活性指标的正常化相关。6.确定eNO是否与EBC测量的炎症、氧化应激和嗜酸性粒细胞活性相关。7.评价通过临床和肺功能参数评估的eNO持续较低的不良反应者是否将通过EBC指标（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失衡）进行表征。8.评价通过临床和肺功能参数评估的具有持续高eNO的良好应答者是否将通过酸度降低、氧化应激降低、炎症降低和嗜酸性粒细胞活性降低的EBC指标表征。