Utility of nasal steroids for treatment of childhood obstructive sleep apnea

描述（由申请人提供）：儿童阻塞性睡眠呼吸暂停综合征（OSAS）很常见，发生率为1-3%的儿童。主要的治疗方法是腺扁桃体切除术，这是侵入性的，并且与发病率相关。因此，替代治疗方案将是非常可取的。一些研究表明，鼻内皮质类固醇（NCS）可能有效治疗儿童阻塞性睡眠呼吸暂停症。然而，这些研究受到规模小、缺乏随机化和盲法、短期随访、仅涉及非常轻微的OSAS儿童以及缺乏对特应性存在的分层的限制。因此，我们建议进行一项随机对照试验，评估NCS与安慰剂在轻度至中度OSAS儿童中的疗效和安全性。我们的总体假设是，NCS在治疗轻至中度儿童阻塞性睡眠呼吸暂停（OSAS）中是安全有效的，特别是哮喘/特应性儿童，但需要持续的维持治疗。具体来说，我们的目标是：(1)。确定NCS与安慰剂治疗儿童OSAS的疗效。我们假设，与随机分配给安慰剂的儿童相比，随机分配给NCS的OSAS儿童的OSAS将得到改善，这是由呼吸暂停低通气指数（AHI）衡量的，这是主要结局。我们还假设其他多导睡眠图参数、OSAS症状、神经认知和行为症状、生活质量和鼻腔症状与安慰剂相比会随着NCS的使用而减少，并且鼻/口咽气道大小会增加。(2)。确定哪些因素会影响对NCS的反应。我们假设哮喘/特应性儿童比非特应性儿童对NCS有更大的反应。此外，我们假设对NCS的反应在气道中具有“高th2”表型的哮喘受试者中最大。此外，我们将确定肥胖受试者对NCS的反应(3)确定NCS与安慰剂治疗儿童OSAS的长期效果。我们假设NCS的作用时间有限，但持续的治疗将导致OSAS持续缓解。(4)。确定阻塞性睡眠呼吸暂停症儿童慢性使用NCS的相关副作用。我们假设所使用剂量的NCS不会导致大量严重不良事件。本研究将通过评估神经认知和行为结果以及多导睡眠图结果来评估NCS对“现实世界”的影响。这将是第一个观察NCS治疗OSAS的长期结果，包括副作用的研究。此外，这项跨学科研究利用了一群经验丰富的研究人员和顾问，包括那些在睡眠医学，遗传学，过敏/免疫学，耳鼻喉科，骨骼健康，眼科和内分泌学方面的专家。这项研究最终将有助于更好地管理儿童阻塞性睡眠呼吸暂停症。该提案的创新方面包括评估NCS治疗OSAS的机制，以及预测NCS反应的个体因素，这可能最终导致个性化医疗方法。

DESCRIPTION (provided by applicant): The childhood obstructive sleep apnea syndrome (OSAS) is common, occurring in 1-3% of children. The primary treatment is adenotonsillectomy, which is invasive and associated with morbidity. Thus, alternative therapeutic options would be highly desirable. Several studies have suggested that intranasal corticosteroids (NCS) may be effective in the treatment of childhood OSAS. However, these studies have been limited by small size, lack of randomization and blinding, short-term follow-up, involvement of children with only very mild OSAS, and lack of stratifying for the presence of atopy. We therefore propose a randomized controlled trial evaluating the efficacy and safety of NCS vs placebo in children with mild to moderate OSAS. Our overall hypothesis is that NCS will be safe and efficacious in the treatment of mild to moderate childhood OSAS, particularly in children with asthma/atopy, but will require ongoing maintenance therapy. Specifically, we aim to: (1). Determine the efficacy of NCS vs placebo in treating OSAS in children. We hypothesize that children with OSAS randomized to NCS will have an improvement in OSAS compared to children randomized to placebo, as measured by the apnea hypopnea index (AHI), the primary outcome. We also hypothesize that other polysomnographic parameters, symptoms of OSAS, neurocognitive and behavioral symptoms, quality of life and nasal symptoms will decrease with NCS use as compared to placebo, and that naso/oropharyngeal airway size will increase. (2). Determine which factors modify the response to NCS. We hypothesize that asthmatic/atopic children will have a greater response to NCS than non-atopic children. Furthermore, we hypothesize that the response to NCS will be greatest in asthmatic subjects with a "Th2-high" phenotype in their airways. In addition, we will determine the response to NCS in obese subjects (3) Determine the long-term effect of NCS vs placebo in the treatment of OSAS in children. We hypothesize that NCS will have a limited duration of action, but that ongoing therapy will result in continued remission of OSAS. (4). Determine the side-effects associated with chronic NCS use in children with OSAS. We hypothesize that NCS in the dosage used will not result in a significant number of serious adverse events. This study will evaluate the "real world" implications of NCS by evaluating neurocognitive and behavioral outcomes in addition to polysomnographic outcomes. This will be the first study to look at the long-term outcomes of NCS for OSAS, including side-effects. In addition, this interdisciplinary study takes advantage of a group of experienced investigators and consultants, including those with expertise in sleep medicine, genetics, allergy/immunology, otolaryngology, bone health, ophthalmology and endocrinology. The study will ultimately lead to better management of OSAS in children. Innovative aspects of the proposal include evaluation of the mechanisms for NCS in treating OSAS, and the individual factors predicting response to NCS, which may ultimately lead to personalized medicine approaches.