ORBEX: Primary Prevention of Asthma and Wheezing in Children-DCC

 描述(由申请人提供)：在过去的25年里，我们对儿童哮喘发病机制的了解取得了重大进展。来自几个出生队列的有力证据表明，大多数持续性儿童哮喘病例始于生命的前3年；这种疾病最初表现为鼻病毒阳性的喘息性下呼吸道疾病(WLRI)；它与早期过敏反应密切相关。研究还表明，与更严重的儿童哮喘相关的不可逆转的肺功能改变和呼吸道重塑的最初迹象都最早出现在学龄前几年。最近的流行病学研究表明，在生命早期增加细菌暴露的环境和住所对早期WLRI和哮喘具有保护作用，但负责这种保护的具体成分尚不清楚。在欧洲，八种致病菌(Bronchovaxom(R))的口服冷冻干燥、解毒提取物已被经验用于预防呼吸道疾病。最近对有哮喘样症状的学龄前儿童的研究表明，Bronchovaxom在预防WLRI方面有很强的效果。我们提出了口服细菌提取物(ORBEX)：儿童哮喘和喘息的初级预防试验，以验证给6-18个月哮喘高危儿童服用Bronchovaxom可以防止3.5-4.5岁儿童持续喘息的假设。我们将进行一项随机、双盲、安慰剂对照的双臂临床试验，共1076例 1.评估连续两年给予高危婴儿每月10天的Bronchovaxom(R)能否延长治疗后第三个观察年内首次WLRI发生的时间(主要结果)，以及治疗后WLRI的发生率是否会降低。2.确定Bronchovaxom(R)是否可以减少参与者在研究的头两年接受研究药物时的WRLI的发生时间和发生率；是否可以减少治疗期间和治疗后观察年内严重WLRI的发生时间和发生率；是否可以在研究药物治疗的两年和治疗后的观察年内使用“无发作日”来减少哮喘样症状。3.评价婴幼儿在学龄前持续使用Bronchovaxom(R)的安全性和耐受性。

 DESCRIPTION (provided by applicant): Major advances have been made in the last 25 years in our understanding of the pathogenesis of childhood asthma. Strong evidence from several birth cohorts indicates that most cases of persistent childhood asthma start in the first 3 years o life; that the disease first manifests as rhinovirus-positive wheezing lower respiratory illnesses (WLRI); and that it is strongly associated with early allergic sensitization. It has also been show that both the non-reversible changes in lung function associated with the more severe forms of childhood asthma and the initial signs of airway remodeling first appear during the preschool years. Recent epidemiological studies have shown that settings and dwellings that increase bacterial exposure in early life are protective against early WLRI and asthma, but the specific components responsible for this protection are unknown. Oral lyophilized, detoxified extracts of eight pathogenic bacteria (Bronchovaxom(r)) have been used empirically in Europe for the prevention of respiratory illnesses. Recent studies in preschoolers with asthma-like symptoms have suggested that Bronchovaxom has a strong effect in the prevention of WLRI. We propose the Oral Bacterial Extracts (ORBEX): Primary Prevention of Asthma and Wheezing in Children trial to test the hypothesis that Bronchovaxom, given to 6-18 month old children at high risk for asthma, can prevent the development of persistent wheezing by age 3.5-4.5 years. We will perform a randomized, double-blind, placebo-controlled, two arm clinical trial with a total of 1076 children with the following specific aims: 1. To evaluate if Bronchovaxom(r) given to high risk infants for 10 days monthly for two consecutive years can increase time to occurrence of the first WLRI episode during a third observation year after therapy (primary outcome) and whether the rate of WLRI will be reduced after therapy. 2. To determine if: Bronchovaxom(r) can reduce the time to occurrence and the rate of WRLI while the participants are receiving study drug during the initial two years of the study; can reduce the time to occurrence and rates of severe WLRI both during therapy and during the observation year after therapy; can reduce asthma-like symptoms using `episode-free days' during both the two years on study drug and during the observation year after therapy. 3. To evaluate the safety and tolerability of the sustained use of Bronchovaxom(r) in infancy through the preschool years.