Utility of nasal steroids for treatment of childhood obstructive sleep apnea

描述(申请人提供)：儿童阻塞性睡眠呼吸暂停综合征(OSAS)是常见的，发生在1-3%的儿童。主要的治疗方法是扁桃体切除术，这是一种侵袭性的治疗方法，且与发病率有关。因此，替代治疗方案将是非常可取的。多项研究表明，鼻内皮质类固醇(NCS)治疗儿童阻塞性睡眠呼吸暂停低通气综合征可能有效。然而，这些研究受到以下因素的限制：规模小、缺乏随机性和盲目性、短期随访、仅涉及非常轻微的OSAS儿童，以及缺乏对特应性反应的分层。因此，我们提出了一项随机对照试验，评估NCS与安慰剂在轻度至中度OSAS儿童中的有效性和安全性。我们的总体假设是，NCS在治疗轻度至中度儿童OSAS方面将是安全和有效的，特别是在患有哮喘/特应性疾病的儿童中，但需要持续的维持治疗。具体来说，我们的目标是：(1)。确定NCS与安慰剂治疗儿童阻塞性睡眠呼吸暂停综合征的疗效。我们假设，与随机接受安慰剂治疗的儿童相比，随机接受NCS治疗的OSAS儿童在OSAS方面将有改善，这是通过主要结果-呼吸暂停低通气指数(AHI)来衡量的。我们还假设，与安慰剂相比，使用NCS会降低其他多导睡眠参数、OSAS症状、神经认知和行为症状、生活质量和鼻部症状，而鼻腔/口咽呼吸道大小将增加。(2)。确定哪些因素会修改对NCS的响应。我们假设哮喘/特应性儿童会比非特应性儿童对NCS有更大的反应。此外，我们假设哮喘受试者对NCS的反应将在他们的呼吸道具有“Th2高”表型的哮喘患者中最大。此外，我们将确定肥胖受试者对NCS的反应(3)确定NCS与安慰剂在儿童OSAS治疗中的长期效果。我们假设NCS的作用时间有限，但正在进行的治疗将导致OSAS的持续缓解。(4)。确定与阻塞性睡眠呼吸暂停综合征儿童长期使用NCS相关的副作用。我们假设NCS在使用剂量上不会导致大量的严重不良事件。这项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的“现实世界”含义。这将是第一项关于非药物治疗阻塞性睡眠呼吸暂停综合征的长期结果的研究，包括副作用。此外，这项跨学科研究利用了一批经验丰富的研究人员和顾问，其中包括在睡眠医学、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具有专业知识的人。这项研究最终将导致对儿童OSAS的更好管理。该提案的创新方面包括评估NCS治疗OSAS的机制，以及预测NCS对NCS的反应的个人因素，这可能最终导致个性化的药物方法。

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.