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

已知患有唐氏综合征（DS）的儿童患阻塞性睡眠呼吸暂停（OSA）的风险非常高， 发病率高达66%。OSA与神经认知障碍和健康受损有关- 相关生活质量（HR-QOL）的儿童DS。DS儿童OSA的当前治疗方法包括 腺样体切除术和气道正压通气（PAP）治疗。不幸的是，治疗效果 局限于腺样体切除术后残留OSA的高风险和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受损相关。 需要有针对性的治疗来减轻OSA对DS儿童的这些负面影响。气道张力减退 在睡眠中被认为是导致DS儿童OSA的原因之一。与此相一致，OSA治疗 旨在通过舌下神经刺激改善气道紧张度， DS.然而，考虑到多次翻修， 手术可能是必要的，在年幼的儿童，以适应随着时间的推移增长。的组合 托莫西汀和奥昔布宁（ato-oxy）可改善睡眠期间的气道张力，并治疗成人OSA 没有DS考虑到这两种药物在儿童中的常规使用和良好的耐受性，我们假设， 奥施康定将是治疗DS儿童OSA的有效药物，并将改善神经认知功能 和HR-QOL。该项目在R61阶段的具体目标包括： 阿托莫西汀治疗DS儿童OSA远期疗效目的2：评价利多卡因的近期疗效 阿托伐他汀治疗对改善DS和OSA儿童HR-QOL的作用本项目的具体目标 R33阶段包括：目标3：评估阿托氧治疗儿童阻塞性睡眠呼吸暂停综合征的长期疗效 在DS目的4：评价阿托莫西汀治疗对改善儿童HR-QOL的长期疗效。 DS和OSA。目的5：评价阿托氧治疗对改善脑梗死儿童神经认知功能的疗效。 DS和OSA。如果成功，该项目将确定一种治疗DS儿童OSA的新方法， 以药物为基础的路线，以改善儿童的认知与DS。

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.