Validation of Urinary Biomarkers in Diagnosis of Pediatric OSA

尿液生物标志物在儿童 OSA 诊断中的验证

• 批准号: 8072918
• 负责人: David Gozal
• 金额: $ 46.44万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072918
• 关键词: Affect; Algorithms; Arousal; Biological Assay; Biological Markers; Cardiovascular system; Child; Childhood; Classification; Clinical; Clinical Markers; Development; Diagnosis; Diagnostic; Early treatment; Enzyme-Linked Immunosorbent Assay; Event; Goals; Guns; Hypercapnia; Hypoxemia; Individual; Instruction; Intervention; Laboratories; Learning; Metabolic; Methods; Morbidity - disease rate; Obstruction; Obstructive Sleep Apnea; Patients; Performance; Phenotype; Physical Examination; Polysomnography; Prevention; Principal Investigator; Procedures; Proteins; Proteome; Proteomics; Recording of previous events; Risk; Screening procedure; Sleep; Snoring; Symptoms; Testing; Training; United States; Urine; Validation; base; cohort; human population study; neurobehavioral; pre-clinical; prospective; treatment response; urinary; validation studies

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."

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)。这种疾病的特征是睡眠期间反复发生上呼吸道部分或完全阻塞，导致高碳酸血症、低氧血症和觉醒反复发作，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 儿童方面非常不可靠。因此，当前 OSA 的诊断方法需要过夜多导睡眠图 (PSG)。该过程繁重、相对不可行、劳动强度大且不方便，导致等待时间长，并不必要地延误诊断和治疗。开发能够可靠区分 PS 儿童和 OSA 儿童的非侵入性生物标志物将极大地促进儿童 OSA 的及时筛查和诊断。我们最近发现，患有 OSA 的儿童晨尿中存在一组差异表达的蛋白质，与患有 PS 的儿童或不打鼾的健康儿童相比，这些蛋白质似乎能够可靠地识别患有 OSA 的儿童。在此应用中，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，并建议使用鸟枪蛋白质组学进一步扩大 OSA 存在特异性的候选蛋白质的数量随后在 160 名儿童中使用常规定量蛋白质测定（例如 RIA 或 EIA）进一步确认，并在随后的儿科队列中进一步进行验证。拟议的研究将有助于开发一种非侵入性、可靠且可能廉价的方法来筛查和诊断儿童 OSA，从而促进及时治疗和预防 OSA 相关疾病。相关性（参见说明）：我们相信，我们的应用程序对指定目标具有高度响应性，如“验证临床前和/或临床标志物，用于回顾性和/或前瞻性人群研究中的早期诊断和干预”。识别个体进行早期干预、预测治疗反应以及优化个体患者治疗的目标。”