AIMS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。学龄前儿童反复发作的喘息有不同的长期预后。大多数儿童在6岁时停止喘息，只有14%的儿童在生命的前3年继续喘息到6岁。因此，大多数早期患有喘息的儿童不会继续患有持续性喘息（即哮喘）。然而，反复发作的喘息影响着儿童及其家庭的生活。虽然这些患者中的大多数似乎不适合长期哮喘控制治疗，因为他们在哮喘发作之间通常完全没有气道高反应性症状，但有必要进行干预，以改变RTI向严重喘息发作的进展。文献中包含了许多试验，探索了针对这种临床情况的各种干预措施，包括在症状出现时口服皮质类固醇，在症状出现至少48小时后口服皮质类固醇，以及在RTI症状出现时吸入皮质类固醇。这些研究中的大多数表明，这些干预措施通常有利于减轻下呼吸道症状。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复杂化。考虑到这一问题的临床重要性，设计良好的前瞻性试验和足够的样本量是解决这一问题的关键。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用性，使其成为一种潜在的急性干预措施，据我们所知，尚未被探索。本研究的选择设计是一项随机、双盲、双虚拟、安慰剂对照的平行比较，旨在减少12-59月龄有中度至重度喘息发作史的儿童急性呼吸道感染期间喘息症状的三种策略。将有两周的观察期来确定和描述儿童。在出现rti相关症状的第一个迹象时，儿童将随机接受三种治疗中的一种，持续7天：活性吸入皮质类固醇（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(孟鲁司特（Singulair） 4毫克每日1次（颗粒剂适用于12-23个月大的儿童，咀嚼片适用于24-59个月大的儿童）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.