Medications for Obstructive Sleep Apnea to Improve Cognition in Children with Down Syndrome (MOSAIC DS)

众所周知，患有唐氏综合症(DS)的儿童患阻塞性睡眠呼吸暂停(OSA)的风险非常高，具有 流行率高达66%。阻塞性睡眠呼吸暂停综合征与神经认知障碍和健康受损有关- DS儿童相关生活质量的研究目前治疗DS儿童阻塞性睡眠呼吸暂停的方法包括 扁桃体切除和正压(PAP)治疗。不幸的是，治疗的有效性是 受限于扁桃体切除术后OSA残留的高风险以及对PAP治疗的依从性差。OSA是 在DS儿童中普遍存在，并与神经认知障碍和HR-QOL受损有关。 需要有针对性的治疗来减轻阻塞性睡眠呼吸暂停综合征儿童的这些负面影响。呼吸道低张 睡眠时间已被确定为DS儿童OSA的原因之一。与此一致的是，OSA治疗 旨在通过舌下神经刺激改善气道张力的青少年，似乎是有效的 DS.然而，考虑到多次复习，舌下神经刺激在儿童中的使用可能受到限制。 对于年龄较小的儿童来说，随着时间的推移，可能有必要进行手术来适应生长发育。这两种技术的结合 托莫西汀和奥昔布宁(ATO-oxy)被证明可以改善成人睡眠期间的气道张力，并治疗OSA 没有DS。鉴于这两种药物在儿童中经常使用且耐受性良好，我们假设ATO- Oxy将是治疗DS儿童OSA的有效方法，并将导致神经认知的改善 和HR-QOL。该项目在R61阶段的具体目标包括：目标1：评估短期-- ATO-oxy治疗儿童阻塞性睡眠呼吸暂停综合征的远期疗效。目的2：评价银杏叶提取物的短期疗效 ATO-oxy治疗改善DS和OSA患儿HR-QOL的研究该项目的具体目标是 R33阶段包括：目标3：评估ATO-oxy治疗儿童阻塞性睡眠呼吸暂停的长期疗效 使用DS。目的：评价ATO-oxy疗法改善儿童高血压患者心率-生活质量的远期疗效。 DS和OSA。目的：评价ATO-oxy疗法改善儿童神经认知功能障碍的疗效。 DS和OSA。如果成功，该项目将确定一种治疗患有阻塞性睡眠呼吸暂停综合征的儿童的新方法，以及 以药物为基础的改善DS儿童认知的途径。

Children with Down syndrome (DS) are known to be at very high risk for obstructive sleep apnea (OSA), with a prevalence of up to 66%. OSA has been associated with neurocognitive impairment and impaired health- related quality of life (HR-QOL) in children with DS. Current treatments for OSA in children with DS include adenotonsillectomy and positive airway pressure (PAP) therapy. Unfortunately, treatment effectiveness is limited by a high risk of residual OSA after adenotonsillectomy and poor adherence to PAP therapy. OSA is prevalent among children with DS and is associated with neurocognitive impairment and impaired HR-QOL. Targeted therapies are needed to mitigate these negative effects of OSA in children with DS. Airway hypotonia during sleep has been identified as a cause of OSA in children with DS. Consistent with this, OSA treatment aimed at improving airway tone via hypoglossal nerve stimulation appears to be effective in adolescents with DS. However, use of hypoglossal nerve stimulation may be limited in children given that multiple revision surgeries would likely be necessary in younger children to adjust for growth over time. The combination of atomoxetine and oxybutynin (ato-oxy) was shown to improve airway tone during sleep and treat OSA in adults without DS. Given that both drugs are routinely used and well-tolerated in children, we hypothesize that ato- oxy will be an efficacious treatment for OSA in children with DS and will lead to improvement in neurocognition and HR-QOL. Specific aims of this project during the R61 phase include: Aim 1: To evaluate the short- term efficacy of ato-oxy treatment for OSA in children with DS. Aim 2: To evaluate the short-term efficacy of ato-oxy treatment on improving HR-QOL in children with DS and OSA. Specific aims of this project during the R33 phase include: Aim 3: To evaluate the long-term efficacy of ato-oxy treatment for OSA in children with DS. Aim 4: To evaluate the long-term efficacy of ato-oxy treatment on improving HR-QOL in children with DS and OSA. Aim 5: To evaluate the efficacy of ato-oxy treatment on improving neurocognition in children with DS and OSA. If successful, this project would identify a novel treatment for OSA in children with DS, as well as medication-based route to improve cognition in children with DS.