Validation of Urinary Biomarkers in Diagnosis of Pediatric OSA

描述(申请人提供)：大约2-3%的美国儿童患有阻塞性睡眠呼吸暂停(OSA)。这种情况的特点是在睡眠期间反复发生部分或完全阻塞上呼吸道的事件，导致高碳酸血症、低氧血症和觉醒的反复发作，并导致大量的心血管、代谢和神经行为疾病。习惯性鼾症(PS)是阻塞性睡眠呼吸暂停综合征(OSA)的主要症状，10%-20%的儿童受到影响，临床病史和体格检查在区分OSA和PS儿童方面很不可靠。因此，目前OSA的诊断方法需要夜间多导睡眠图(PSG)。这一程序繁琐，相对不可用，劳动强度大，不方便，导致等待时间长，诊断和治疗不必要的延误。开发能够可靠地区分儿童PS和OSA的非侵入性生物标志物(S)将极大地促进儿童OSA的及时筛查和诊断。我们最近在OSA儿童的晨尿中发现了一组差异表达的蛋白质，与PS或无鼾症的健康儿童相比，这似乎可以可靠地识别OSA儿童。在这项应用中，我们建议使用ELISA法对350-500名儿童的扩大儿科队列中的这些发现进行验证性研究，并建议进一步扩大候选蛋白质的数量，使用枪炮蛋白质组学，然后在160名儿童中使用常规的定量蛋白质分析(如RIA或EIA)进一步确认，并进一步在随后的儿科队列中进行验证。拟议的研究将有助于开发一种非侵入性、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综合征，从而促进及时治疗和预防阻塞性睡眠呼吸暂停综合征相关疾病。相关性(参见说明书)：我们相信，我们的应用程序对指定的目标具有很高的响应性，如“在回顾和/或预期人群研究中验证用于早期诊断和干预的临床前和/或临床标记物的有效性，目的是(S)确定个人进行早期干预、预测治疗反应和优化个别患者的治疗。”

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."