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）。这种病症的特征在于睡眠期间反复发生上呼吸道部分或完全阻塞事件，导致反复发作的高碳酸血症、低氧血症和觉醒，并导致大量心血管、代谢和神经行为疾病。习惯性打鼾（PS）是阻塞性睡眠呼吸暂停（OSA）的主要症状，约有10-20%的儿童有此症状，而临床病史和体格检查在鉴别儿童OSA和PS方面极不可靠。因此，目前OSA的诊断方法需要整夜多导睡眠图（PSG）。该过程是繁重的，相对不可用的，劳动密集型的，并且不方便，导致长时间的等待和诊断和治疗的不必要的延迟。开发能够可靠区分患有PS的儿童与患有OSA的儿童的非侵入性生物标志物将极大地促进儿童中OSA的及时筛查和诊断。我们最近发现，在患有OSA的儿童的晨尿中存在一组差异表达的蛋白质，与患有PS或不打鼾的健康儿童相比，这些蛋白质似乎可以可靠地识别患有OSA的儿童。在本申请中，我们提出了使用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，并且还提出使用鸟枪蛋白质组学进一步扩大特异于OSA存在的候选蛋白质的数量，然后使用常规定量蛋白质测定如RIA或EIA进行进一步确认。并进一步在随后的儿科队列中进行验证。拟议的研究将允许开发一种非侵入性的，可靠的和潜在的廉价的方法，用于筛查和诊断儿童OSA，因此有助于及时治疗和预防OSA相关的疾病。相关性（参见说明）：我们相信，我们的申请对指定目标高度响应，如“验证临床前和/或临床标记物用于回顾性和/或前瞻性人群研究中的早期诊断和干预的应用，其目标是鉴定用于早期干预的个体，预测治疗反应，并优化个体患者的治疗”所示。"