AIMS

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。反复出现喘息的学龄前儿童有不同的长期结局。大多数人会在6岁时停止喘息，只有14%的儿童在生命的前3年会在6岁时继续喘息。因此，大多数早期有喘息的儿童不会继续持续喘息(即哮喘)。然而，反复出现的喘息对儿童及其家庭的生活产生了影响。虽然这些患者中的大多数似乎不是长期哮喘控制器治疗的候选对象，因为他们通常完全健康，没有喘息发作之间的呼吸道高反应性症状，但有必要进行干预，将RTI的进展改变为严重的喘息发作。这些文献包含许多试验，探索针对这种临床情况的各种干预措施，包括症状开始时口服皮质类固醇，症状出现至少48小时后口服皮质类固醇，以及在RTI症状开始时吸入皮质类固醇。这些研究中的大多数表明，这种干预措施通常对减少下呼吸道症状是有益的。然而，小样本量和患者群体的显著异质性使这些发现的解释变得复杂。鉴于这一问题的临床重要性，一项设计良好、样本量充足的前瞻性试验对于解决这一问题至关重要。此外，白三烯在病毒感染相关的喘息和哮喘中的作用的新证据，以及有效的白三烯受体拮抗剂的可获得性，使这一潜在的急性干预措施，据我们所知，尚未被探索。这项研究的选定设计是三种策略的随机、双盲、双安慰剂对照的平行比较，这些策略旨在减少12-59个月大、有中到重度喘息史的儿童在急性RTI期间的喘息症状。将有两周的观察期来确定儿童的资格和特征。首次出现RTI相关症状时，儿童将随机接受三种治疗之一，为期7天：1.主动吸入皮质类固醇(ICS)(布地奈德(Pulmicort ResPules 1.0 mg Bid)和安慰剂白三烯受体拮抗剂(LTRA)，或2.活性LTRA(Montelukast)(Singulair 4 mg每天一次(12-23个月大的儿童颗粒剂和24-59个月大的儿童咀嚼片剂))和安慰剂ICS，或3.安慰剂ICS和安慰剂LTRA。

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. Preschool aged children with recurrent episodes of wheezing have different long-term outcomes. Most will stop wheezing by 6 years of age, with only 14% of children who wheeze during the first 3 years of life continuing to wheeze at 6 years of age. Thus, most children with wheezing early in life do not go on to have persistent wheezing (i.e. asthma). Nevertheless, the recurrent wheezing episodes impact upon the lives of children and their families. While most of these patients would not appear to be candidates for long-term asthma controller therapy, as they are generally entirely well without symptoms of airway hyper-reactivity between episodes of wheezing, an intervention to alter the progression of RTI to severe wheezing episodes is necessary. The literature contains numerous trials exploring a variety of interventions for this clinical situation, including oral corticosteroids at symptom onset, oral corticosteroids after symptoms present for a least 48 hours, and inhaled corticosteroids at onset of RTI symptoms. The majority of these studies suggest that such interventions are generally beneficial in reducing lower respiratory tract symptoms. However, small sample sizes and significant heterogeneity of the patient populations complicate the interpretation of these findings. Given the clinical importance of this issue, a well-designed prospective trial with adequate sample size is critical to address this problem. In addition, emerging evidence of the role of leukotrienes in viral infection associated wheezing as well as asthma, along with the availability of potent leukotriene receptor antagonists, makes this a potential acute intervention which has not yet, to our knowledge, been explored. The selected design of this study is a randomized, double-blind, double-dummy placebo-controlled parallel comparison of three strategies directed at minimizing symptoms of wheezing during acute RTIs in children 12-59 months of age with histories of moderate-severe episodes of wheezing. There will be a 2-week observation period to qualify and characterize children. Children will be randomized to one of three treatments for 7 days at the first-sign of RTI-associated symptoms: 1. Active inhaled corticosteroid (ICS) (budesonide (Pulmicort Respules 1.0 mg BID)and placebo leukotriene receptor antagonist (LTRA), or 2. Active LTRA (montelukast (Singulair 4 mg once daily (Granules for children 12-23 months of age and chewable tablets for children 24-59 months of age) and placebo ICS, or 3. Placebo ICS and placebo LTRA.