Sleep-disordered breathing (SDB), a condition affecting at least 2-3% of children ages 2- 10 years, is associated with substantial neurocognitive and learning deficits. While the mechanisms underlying such deficits are still being delineated, they do involve recruitment of systemic and regional inflammatory and oxidative processes. However, not all children with SDB present cognitive deficits, implying that individual and environmental determinants of susceptibility also account for the variance in SDB phenotype. Based on exciting preliminary findings suggesting a recognizable and distinct phenotype for obese and non-obese children with SDB, we now propose that SDB will particularly induce systemic inflammatory responses in obese children, and that the magnitude of such inflammatory responses will be the major determinant of cognitive and endothelial dysfunction. We therefore will (i) determine whether 5-8 year-old community-recruited otherwise healthy obese children with and without SDB display increases in plasma inflammatory markers and fat derived adipokines, when compared to non-obese children with and without SDB. Specifically, we will examine IL-6, TNF-1, and ApoE polymorphisms, as well as plasma levels of IL-6, TNF-1 , soluble CD40 ligand, and high sensitivity CRP, and adipokines such as leptin, adiponectin, resistin, visfatin, and ghrelin.;(ii) establish whether changes in these inflammatory markers are associated with neurocognitive deficits and endothelial function alteration. These studies will identify predictive biological correlates of cognitive and vascular morbidities in a large population of obese 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, ponderal status, physical findings, and biological markers. Such approaches may lead to timely recognition of SDB and prevention of its associated morbidities in both obese and non-obese children.

Public Health Relevance

Sleep apnea is a frequent condition in children, and in recent years has been identified as causing significant problems, such as learning deficits, elevated blood pressure and many other adverse consequences, all of which lead to decreased quality of life. Obesity, which has reached epidemic proportions in the pediatric US population, is a major risk factor for sleep apnea. In this project, we propose to examine whether obese children are not only at risk for sleep apnea, but more importantly are also at increased risk for the intellectual and cardiovascular adverse consequences of sleep apnea through increased activation of inflammatory processes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065270-11
Application #
8527819
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Twery, Michael
Project Start
1999-09-30
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
11
Fiscal Year
2013
Total Cost
$454,794
Indirect Cost
$163,259
Name
University of Chicago
Department
Pediatrics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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