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.
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."
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