Cognitive Function in Snoring Children

描述（由申请人提供）：睡眠呼吸障碍（SDB）是一种影响至少2-3%的2- 10岁儿童的疾病，与大量神经认知和学习缺陷相关。虽然这种缺陷的机制仍在描述中，但它们确实涉及全身和区域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，这意味着易感性的个体和环境决定因素也可以解释SDB表型的差异。基于令人兴奋的初步研究结果表明，一个可识别的和不同的表型的肥胖和非肥胖儿童的SDB，我们现在提出，SDB将特别诱导全身炎症反应的肥胖儿童，这种炎症反应的程度将是认知和内皮功能障碍的主要决定因素。因此，我们将（i）确定与患有和不患有SDB的非肥胖儿童相比，患有和不患有SDB的5-8岁社区招募的其他健康肥胖儿童是否显示血浆炎症标志物和脂肪衍生的脂肪因子增加。具体地说，我们将检测IL-6、TNF-1和ApoE多态性，以及IL-6、TNF-1、可溶性CD 40配体和高敏C反应蛋白的血浆水平，以及脂肪因子如瘦素、脂联素、内脂素、内脂素和生长素释放肽。(ii)确定这些炎症标志物的变化是否与神经认知缺陷和内皮功能改变相关。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针对打鼾儿童的基于治疗的临床算法，该算法采用经过验证的症状、体重状态、身体检查结果和生物标记物的组合。这些方法可能导致在肥胖和非肥胖儿童中及时识别SDB并预防其相关的发病率。

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.