The obstructive sleep apnea syndrome (OSAS) is a common cause of morbidity in childhood. However, its pathophysiology is poorly understood. It is hypothesized that changes in upper airway neuromotor tone during development play a major role in the maintenance of upper airway patency during sleep, and the expression of sleep-disordered breathing. The following hypotheses will be tested during sleep: (1) That, in normal subjects, upper airway collapsibility is lowest during childhood and increases with age, with a critical transition occurring during adolescence. The decreased collapsibility noted during childhood is due primarily to increased upper airway reflex neuromotor tone. Specifically, in normal, non-snoring subjects, we will (a) Establish baseline differences in UA function between children and adults in the hypotonic condition; (b) Examine the effects of UA reflexes on UA patency in normal children compared to adults, and (c) Determine the effect of puberty on UA collapsibility. (2) That OSAS develops in children lacking these protective upper airway reflexes. Specifically, in normal children compared to children with OSAS, we will (a) Establish baseline differences in UA function in the hypotonic condition, (b) Determine the role of REM sleep on UA collapsibility, and (c) Examine the effects of UA reflexes on UA patency. (3) That regulation of neuromotor tone, and the central response to an upper airway load, accounts for the polysomnographic characteristics of sleep-disordered breathing unique to childhood OSAS. Specifically, we will (a) Examine the effects of UA reflexes on UA patency in children with obstructive hypoventilation (OH) vs children with discrete, cyclical obstructive apneas (OA), (b) Measure the arousal threshold to an inspiratory resistive load in children with OH vs OA, and (c) Measure the respiratory-related evoked potentials (RREP) in response to inspiratory occlusion during sleep in children with OA vs OH and controls. These studies will help elucidate the underlying pathophysiology of childhood OSAS, resulting in better understanding and improved management of this disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058585-09
Application #
7068052
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Twery, Michael
Project Start
1998-07-06
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2008-04-30
Support Year
9
Fiscal Year
2006
Total Cost
$313,460
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
Marcus, Carole L (2014) Arousal threshold in obstructive sleep apnea. Am J Respir Crit Care Med 189:372-3

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