The obstructive sleep apnea syndrome (OSAS) is a common cause of morbidity in the pediatric population This proposal will integrate studies of neuromotor control of the upper airway (UA) and UA structure in order to provide a comprehensive assessment of all pathophysiologic risk factors for OSAS in the same individual, and to apply this knowledge to high risk pediatric patients. The proposal focuses on the effects of obesity during the transitional period of adolescence. The overall hypothesis is that OSAS develops when a structural load is acquired by an individual with an underlying impairment of UA neuromotor function. This will be a 1:1:1 matched case-dual control study with a complementary interventional component. UA reflexes will be determined by measuring the difference between the UA pressure-flow response during sleep in the activated vs the hypotonic state, and the UA response to hypercapnia. UA size and structure will be determined using MRI.
In Aim 1, we will determine the contribution of UA reflexes to the apnea hypopnea index (AHI) by conducting a cross-sectional, case control study that will compare obese, adolescent cases with OSAS to (i) non-snoring, BMI-matched obese controls and to (ii) non-obese, non-snoring controls. We hypothesize that UA reflexes will be decreased in obese adolescents with OSAS compared to obese controls, and that UA reflexes will be greater in obese controls than in non-obese controls.
In Aim 2 A, we will determine the contribution of structural UA narrowing to the AHI. We hypothesize that the UA will be narrower in obese adolescents with OSAS compared to obese controls.
In Aim 2 B, we will identify the most important structural factors leading to upper airway narrowing. We hypothesize that adenotonsillar tissue and regional distribution of adipose tissue are the prime determinants of UA size in adolescents.
In Aim 3, we will determine the effects of weight loss on OSAS.
In Aim 3 A, we will determine whether the degree of weight loss correlates with the change in AHI. We hypothesize that the greater the weight loss, the greater the fall in AHI.
In Aim 3 B, we will determine whether the decrease in AHI following weight loss is due primarily to a change in UA reflexes or a change in UA size. We hypothesize that the improvement in AHI following weight loss is due primarily to an increase in UA size rather than to a change in UA reflexes.
In Aim 3 C, we will determine the effect of weight loss on UA structure. We hypothesize that weight loss will result primarily in a decrease in the size of the parapharyngeal fat pads, but may also affect tongue and soft palate size. These studies will help elucidate the pathophysiology of OSAS in obese adolescents, ultimately resulting in improved management of this disease.

Public Health Relevance

The current obesity epidemic in the United States is resulting in an increasing prevalence of the obstructive sleep apnea syndrome (OSAS) in adolescents. This study will help elucidate of the causes of OSAS in teenagers, and determine the effectiveness of weight loss in ameliorating these causative factors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058585-12
Application #
8133457
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Lewin, Daniel S
Project Start
1998-07-06
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
12
Fiscal Year
2011
Total Cost
$577,609
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Busch, David R; Lynch, Jennifer M; Winters, Madeline E et al. (2016) Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome. Sleep 39:209-16
Konstantinopoulou, Sofia; Tapia, Ignacio E; Kim, Ji Young et al. (2016) Relationship between obstructive sleep apnea cardiac complications and sleepiness in children with Down syndrome. Sleep Med 17:18-24
Xanthopoulos, Melissa S; Gallagher, Paul R; Berkowitz, Robert I et al. (2015) Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea. Sleep 38:401-10
Tapia, Ignacio E; McDonough, Joseph M; Huang, Jingtao et al. (2015) Respiratory cortical processing to inspiratory resistances during wakefulness in children with the obstructive sleep apnea syndrome. J Appl Physiol (1985) 118:400-7
Cielo, Christopher M; Marcus, Carole L (2015) Obstructive sleep apnoea in children with craniofacial syndromes. Paediatr Respir Rev 16:189-96
Schwab, Richard J; Kim, Christopher; Bagchi, Sheila et al. (2015) Understanding the anatomic basis for obstructive sleep apnea syndrome in adolescents. Am J Respir Crit Care Med 191:1295-309
Koren, D; Chirinos, J A; Katz, L E L et al. (2015) Interrelationships between obesity, obstructive sleep apnea syndrome and cardiovascular risk in obese adolescents. Int J Obes (Lond) 39:1086-93
King, Michelle S; Xanthopoulos, Melissa S; Marcus, Carole L (2014) Improving Positive Airway Pressure Adherence in Children. Sleep Med Clin 9:219-234
Thongyam, Anchana; Marcus, Carole L; Lockman, Justin L et al. (2014) Predictors of perioperative complications in higher risk children after adenotonsillectomy for obstructive sleep apnea: a prospective study. Otolaryngol Head Neck Surg 151:1046-54
Kureshi, Suraiya A; Gallagher, Paul R; McDonough, Joseph M et al. (2014) Pilot study of nasal expiratory positive airway pressure devices for the treatment of childhood obstructive sleep apnea syndrome. J Clin Sleep Med 10:663-9

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