Validation of Urinary Biomarkers in Diagnosis of Pediatric OSA

描述（由申请人提供）：在美国，大约2-3%的儿童患有阻塞性睡眠呼吸暂停（OSA）。这种情况的特征是睡眠期间上呼吸道部分或完全阻塞反复发生，导致反复发作的高碳酸血症、低氧血症和觉醒，并导致严重的心血管、代谢和神经行为疾病。习惯性打鼾（PS）是OSA的主要症状，影响10-20%的儿童，临床病史和体格检查在区分OSA和PS儿童时往往不可靠。因此，目前的OSA诊断方法需要夜间多导睡眠图（PSG）。该程序繁琐，相对难以获得，劳动密集，不方便，导致长时间等待和不必要的延误诊断和治疗。能够可靠地区分PS儿童与OSA儿童的无创生物标志物的开发将极大地促进儿童OSA的及时筛查和诊断。我们最近发现，在OSA儿童晨尿中存在一组差异表达蛋白，这似乎可以可靠地将OSA儿童与患有PS或不打鼾的健康儿童区分开来。在本申请中，我们建议使用ELISA方法在350-500名儿童的扩大儿科队列中对这些发现进行验证研究，并建议使用散弹枪蛋白质组学进一步扩大OSA存在特异性候选蛋白的数量，然后使用常规定量蛋白分析（如RIA或EIA）在160名儿童中进一步确认，并在随后的儿科队列中进一步验证。拟议的研究将允许开发一种无创、可靠和潜在廉价的方法来筛查和诊断儿童阻塞性睡眠呼吸暂停，从而促进及时治疗和预防阻塞性睡眠呼吸暂停相关发病率。相关性（见说明书）：我们相信我们的应用高度符合指定目标，如“在回顾性和/或前瞻性人群研究中用于早期诊断和干预的临床前和/或临床标记的验证，目的是确定早期干预的个体，预测治疗反应，并优化个体患者的治疗”所示。

DESCRIPTION (provided by applicant): Approximately 2-3% of all children In the United States suffer from obstructive sleep apnea (OSA). This condition is characterized by repeated events of partial or complete obstruction ofthe upper airways during sleep leading to recurring episodes of hypercapnia, hypoxemia, and arousal, and leads to substantial cardiovascular, metabolic, and neurobehavioral morbidities. Habitual snoring (PS), the major symptom of OSA, affects 10-20% of children, and clinical history and physical examination are marl^edly unreliable In differentiating between children with OSA and PS. Thus, current diagnostic approaches for OSA require overnight polysomnography (PSG). This procedure Is onerous, relatively unavailable, labor Intensive, and inconvenient, leading to long waiting periods and unnecessary delays in diagnosis and treatment. Development of non-Invasive biomarker(s) capable of reliably distinguishing children with PS from those with OSA would greatly facilitate timely screening and diagnosis of OSA in children. We have recently shown the presence of a cluster of differentially expressed proteins in the morning urine of children with OSA that appears to reliably identify those children with OSA compared to those children with either PS or non-snoring healthy children. In this application, we propose a validation study of such findings in an expanded pediatric cohort of 350-500 children using ELISA approaches, and also propose to further expand the number of candidate proteins that is specific to the presence of OSA using shot-gun proteomics followed by further confirmation using conventional quantitative protein assays such as RIA or EIA In 160 children, and further followed by verification in a subsequent pediatric cohort. The proposed studies will allow for development of a non-Invasive, reliable and potentially cheap method for screening and diagnosis of OSA in children, and therefore facilitate timely treatment and prevention of OSA-assoclated morbidities. RELEVANCE (See instructions): We believe that our application is highly responsive to the designated objectives as Illustrated by "Validation of pre-clinical and/or clinical markers for applications in eariy diagnosis and intervention in retrospective and/or prospective human population studies with the goal(s) of identifying individuals for early intervention, predicting treatment response, and optimizing treatment for individual patients."