Utility of nasal steroids for treatment of childhood obstructive sleep apnea

鼻类固醇治疗儿童阻塞性睡眠呼吸暂停的效用

• 批准号: 8754788
• 负责人: CAROLE L MARCUS
• 金额: $ 65.14万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-09 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8754788
• 关键词: Adenoidal structure; Adrenal Cortex Hormones; Adult; Adverse effects; Allergens; Apnea; Apoptosis; Asthma; Behavioral; Behavioral Symptoms; Breathing; Child; Childhood; Chronic; Cognitive deficits; Continuous Positive Airway Pressure; Disease; Disease remission; Dust; Edema; Endocrinology; Environmental Irritants; Environmental air flow; Esthesia; Evaluation; Exposure to; Genetic; Genetic Medicine; Glucocorticoid Receptor; Growth; Heart Hypertrophy; Hypersensitivity; Hypertension; Hypertrophy; Immunology; In Vitro; Individual; Infection; Inflammation; Interdisciplinary Study; Interleukin-6; Irritants; Lead; Leukotriene Antagonists; Link; Long-Term Effects; Maintenance Therapy; Measures; Medical; Medicine; Metabolic; Morbidity - disease rate; Neurocognitive; Non obese; Nose; Obesity; Obstruction; Obstructive Sleep Apnea; Operative Surgical Procedures; Ophthalmology; Oropharyngeal; Otolaryngology; Outcome; Phenotype; Placebos; Polysomnography; Production; Quality of life; Randomized; Randomized Controlled Trials; Recurrence; Reflex action; Research Personnel; Residual state; Safety; Serious Adverse Event; Sleep; Smoke; Snoring; Steroids; Symptoms; Therapeutic; Tissues; Tobacco; Tonsil; Tonsillar Tissue; Tumor Necrosis Factor-alpha; airway obstruction; atopy; bone health; cysteinyl leukotriene receptor; cytokine; dosage; experience; follow-up; glucocorticoid receptor alpha; indexing; innovation; mRNA Expression; pressure; primary outcome; public health relevance; receptor expression; response

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.

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，发生在1-3%的儿童中。主要的治疗方法是扁桃体切除术，这是侵入性的，并与发病率有关。因此，替代的治疗选择将是高度期望的。一些研究表明，鼻内皮质类固醇（NCS）可能是有效的治疗儿童OSAS。然而，这些研究受到以下限制：样本量小、缺乏随机化和盲法、短期随访、仅涉及非常轻度的OSAS儿童以及缺乏对特应性存在的分层。因此，我们建议进行一项随机对照试验，评价NCS与安慰剂治疗轻中度OSAS儿童的疗效和安全性。我们的总体假设是，NCS在治疗轻中度儿童OSAS中是安全有效的，特别是在哮喘/特应性儿童中，但需要持续的维持治疗。具体而言，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，与随机分配到安慰剂组的儿童相比，随机分配到NCS组的OSAS儿童的OSAS将得到改善，这是通过呼吸暂停低通气指数（AHI）（主要结局）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图参数、OSAS症状、神经认知和行为症状、生活质量和鼻部症状，并且鼻/口咽气道尺寸会增加。（二）、确定哪些因素会改变对NCS的响应。我们假设哮喘/特应性儿童对NCS的反应比非特应性儿童更大。此外，我们假设，在气道中具有“Th 2-高”表型的哮喘受试者中，对NCS的反应将是最大的。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的持续缓解。（四）、确定OSAS儿童长期使用NCS的副作用。我们假设所用剂量的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的“真实的世界”影响。这将是第一个研究NCS治疗OSAS的长期结果，包括副作用。此外，这项跨学科研究利用了一组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具有专业知识的人。这项研究将最终导致更好地管理儿童OSAS。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。