Study of Acid Reflux Therapy for Children with Asthma

描述(由申请人提供)： 胃食道反流(GER)在哮喘儿童中是常见的，可引起支气管痉挛，并增加呼吸道反应性。患有哮喘的儿童经常用抑制胃酸产生的药物来治疗GER。然而，这种治疗方法很昂贵，而且疗效未经证实。这项建议的主要目标是进行一项多点、随机的临床试验，以验证这样一种假设，即用批准的质子泵抑制剂兰索拉唑治疗GER将减少哮喘控制不佳儿童的恶化频率。这项研究将包括300名使用吸入性皮质类固醇治疗的哮喘儿童，他们的年龄在6-16岁之间，控制不良的定义是频繁的症状、过量使用β-激动剂或频繁的恶化。参与者将被随机分配到兰索拉唑或安慰剂治疗6个月。GER的存在、严重程度及其与哮喘症状的关系将通过24小时食道pH监测来确定，但GER的存在或严重程度不会影响随机治疗。主要的结果衡量标准是参与者根据日记和访谈定义的哮喘恶化的比例。次要结果测量包括哮喘症状和控制评分、GER症状、肺功能和非计划的卫生保健接触。预先定义的亚组分析将检查特定临床特征与兰索拉唑反应之间的关系。 治疗反应还将通过给药后3小时的兰索拉唑血药浓度进行评估，并与细胞色素P450途径CYP2C19和促炎细胞因子IL-1β的多态性有关。第三级研究将确定GER的程度如何影响呼吸道炎症，通过呼气中H(PH)和NO的浓度来衡量。 这项试验的结果应该会对哮喘儿童GER的理解和治疗产生重大影响。

DESCRIPTION (provided by applicant): Gastroesophageal reflux (GER) is frequent in children with asthma, can induce bronchospasm, and increase airways reactivity. Children with asthma are often treated for GER with drugs to suppress gastric acid production. However, this treatment is expensive, and with unproven benefit. The primary objective in this proposal is to conduct a multi-site, randomized, clinical trial to test the hypothesis that treatment of GER with lansoprazole, an approved proton pump inhibitor, will decrease the frequency of exacerbations in children with poorly controlled asthma. The study will include 300 asthmatic children treated with inhaled corticosteroids, 6-16 years of age, with poor control defined by frequent symptoms, excessive beta agonist use, or frequent exacerbations. Participants will be randomly assigned to treatment with either lansoprazole or placebo for six months. The presence, severity, and relationship of GER to asthma symptoms will be determined with 24 hour esophageal pH monitoring, but randomization to treatment will not be influenced by the presences or severity of GER. The primary outcome measure is the proportion of participants who have exacerbations of asthma defined by diaries and interviews. Secondary outcome measures include asthma symptom and control scores, GER symptoms, lung function, and unscheduled health care contacts. Pre-defined subgroup analyses will examine the relationship between specific clinical features and the response to lansoprazole. Treatment response will also be evaluated with 3-hour post-dose plasma lansoprazole concentrations, and related to polymorphisms in CYP2C19, the cytochrome P450 pathway, and IL-1 beta, a pro-inflammatory cytokine. Tertiary studies will determine how the magnitude of GER impacts airways inflammation, as measured by the concentrations of H+ (pH) and NO in expired breath. The results of this trial should have a major impact on the understanding and treatment of GER in children with asthma.