Sleep-disordered breathing (SDB), a condition affecting at least 2-3% of children ages 2-10 years, is associated with delayed diagnosis and treatment, and substantial neurocognitive and learning deficits. However, only a proportion of children with SDB will develop such deficits while the remainder will retain normal or near-normal neurocognitive function. The mechanisms underlying such discrepancy in SDB-associated morbidity are unknown. Based on exciting preliminary findings, we now propose that SDB will induce systemic inflammatory responses, and that the magnitude of such inflammatory response will be the major determinant of the severity of neurocognitive dysfunction associated with SDB. We therefore, will (i) determine whether SDB is associated with increases in inflammatory markers in the serum and urine of 6-8 year-old children. Specifically, we will examine gene expression and serum levels of IL-1beta, IL-8, IL-6, TNFalpha, and ApoE polymorphisms, as well as serum levels of ICAM-1, VCAM, E-selectin, and high sensitivity CRP, and urine levels of 15f2t-lsoprostane in snoring children with varying severity levels of SDB and controls; (ii) in these same children, we will assess whether the magnitude of neurocognitive dysfunction assessed with multiple well validated batteries is positively correlated with particular individual inflammatory markers, and whether a sub-group of such markers exhibits reliable predictive value for SDB-associated neurocognitive dysfunction; (iii) finally, we will establish whether the improvement in neurocognitive function associated with treatment of SDB is paralleled by similar ameliorations in the serum and/or urine levels of the selected inflammatory correlates. These studies will identify highly predictive biological correlates of cognitive morbidity in a large population of children with varying degrees of SDB. Furthermore, they may allow for future development of treatment-based clinical algorithms for snoring children that employ validated combinations of symptoms, physical findings, and biological markers. Such approaches may lead to timely recognition of SDB and prevention of its associated morbidities.
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