Cognitive Function in Snoring Children

描述(由申请人提供)：睡眠障碍呼吸(SDB)是一种影响2-10岁儿童的至少2%-3%的疾病，与严重的神经认知和学习障碍有关。虽然这种缺陷背后的机制仍在描述中，但它们确实涉及系统性和区域性炎症和氧化过程的招募。然而，并不是所有的SDB儿童都存在认知缺陷，这意味着个体和环境的易感性决定因素也解释了SDB表型的差异。基于令人兴奋的初步发现，表明患有SDB的肥胖和非肥胖儿童具有可识别和独特的表型，我们现在提出，SDB特别会在肥胖儿童中诱导全身炎症反应，并且这种炎症反应的大小将是认知和内皮功能障碍的主要决定因素。因此，我们将(I)确定社区招募的有无SDB的5-8岁健康肥胖儿童与有无SDB的非肥胖儿童相比，是否显示出血浆炎症标志物和脂肪衍生脂肪因子的增加。具体地说，我们将检测IL-6、肿瘤坏死因子-1和载脂蛋白E基因多态性，以及血浆IL-6、肿瘤坏死因子-1、可溶性CD40配体和高敏C反应蛋白水平，以及瘦素、脂联素、抵抗素、内脂素和生长激素等脂肪因子的水平。(Ii)确定这些炎症标志物的变化是否与神经认知障碍和内皮功能改变有关。这些研究将在大量患有不同程度SDB的肥胖儿童中确定认知和血管疾病的预测性生物学相关性。此外，它们可能允许未来开发基于治疗的儿童鼾症临床算法，使用症状、体重状况、身体检查结果和生物标记物的有效组合。这种方法可能导致及时认识到SDB，并预防肥胖和非肥胖儿童的相关疾病。

DESCRIPTION (provided by applicant): Sleep-disordered breathing (SDB), a condition affecting at least 2-3% of children ages 2- 10 years, is associated with substantial neurocognitive and learning deficits. While the mechanisms underlying such deficits are still being delineated, they do involve recruitment of systemic and regional inflammatory and oxidative processes. However, not all children with SDB present cognitive deficits, implying that individual and environmental determinants of susceptibility also account for the variance in SDB phenotype. Based on exciting preliminary findings suggesting a recognizable and distinct phenotype for obese and non-obese children with SDB, we now propose that SDB will particularly induce systemic inflammatory responses in obese children, and that the magnitude of such inflammatory responses will be the major determinant of cognitive and endothelial dysfunction. We therefore will (i) determine whether 5-8 year-old community-recruited otherwise healthy obese children with and without SDB display increases in plasma inflammatory markers and fat derived adipokines, when compared to non-obese children with and without SDB. Specifically, we will examine IL-6, TNF-1, and ApoE polymorphisms, as well as plasma levels of IL-6, TNF-1 , soluble CD40 ligand, and high sensitivity CRP, and adipokines such as leptin, adiponectin, resistin, visfatin, and ghrelin.; (ii) establish whether changes in these inflammatory markers are associated with neurocognitive deficits and endothelial function alteration. These studies will identify predictive biological correlates of cognitive and vascular morbidities in a large population of obese children with varying degrees of SDB. Furthermore, they may allow for future development of treatment-based clinical algorithms for snoring children that employ validated combinations of symptoms, ponderal status, physical findings, and biological markers. Such approaches may lead to timely recognition of SDB and prevention of its associated morbidities in both obese and non-obese children.