Obstructive sleep apnea (OSA) is a common disorder, occurring in approximately 1-3% of children and is the result of pharyngeal obstruction during sleep. The prevalence of sleep apnea during childhood is linked to adenotonsillar hypertrophy and an increasing epidemic of obesity. Upper airway obstruction during sleep is the result of deficits in pharyngeal structural properties and/or compensatory neuromuscular. Practice guidelines recommend adenotonsillectomy as first-line therapy for otherwise healthy children with OSA. The cure rates for adenotonsillectomy, however, are highly variable exposing many children to the risks of surgery without clear clinical benefit. Clinicians have been hampered by a lack of diagnostic tests to determine pharyngeal function during sleep and to predict treatment responses. Pharyngeal structural properties and neuromuscular responses can be assessed during sleep by manipulating nasal pressure (Pcrit). These measurements, however, are laborious, and not well tolerated by young children or during REM sleep. Polysomnography is well tolerated by children, however, conventional measures of sleep apnea severity (AHI, arousal index, time spent with ETCO2>50mmHg and SaO2) do not adequately measure the severity of airflow obstruction during sleep to characterize pharyngeal properties. To overcome these deficiencies we have developed sensitive continuous metrics of flow limitation severity in children that will be used in this proposal to assess the pharyngeal structural properties and neuromuscular control, and to predict responses to surgery. Our primary hypothesis is that streamlined methods to characterize upper airway structural and neuromuscular properties will reveal unique pathogenic mechanisms of upper airway obstruction in children during sleep. To address this hypothesis, pharyngeal mechanical and neuromuscular properties will be assessed in children during sleep and validated by comparison to the gold standard pressure-flow relationships (SA1). Pharyngeal neuromechanical properties will be characterized in children with OSA compared to non snoring controls, before and after adenotonsillectomy (SA2) and in obese compared to non obese children (SA3) to determine the impact of these disease modifiers on upper airway obstruction during sleep. Our approach will yield novel streamlined methods to improve the diagnosis and treatment of OSA in children.

Public Health Relevance

Obstructive sleep apnea is a common disorder in children that is linked to adenotonsillar hypertrophy and obesity. The proposal addresses underlying mechanisms of upper airway obstruction during sleep, and will develop novel clinically useful methods for diagnosing obstructive sleep apnea, elucidating its pathogenesis, and predicting responses to adenotonsillectomy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL105895-02
Application #
8212035
Study Section
Special Emphasis Panel (ZHL1-CSR-X (O1))
Program Officer
Laposky, Aaron D
Project Start
2011-01-10
Project End
2015-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$139,704
Indirect Cost
$10,348
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218