Sleep apnea is a common condition with significant morbidity that affects at least 4% of middle-aged males and 2% of middle-aged females. Obesity is thought to be the most important risk factor for obstructive sleep apnea yet we do not understand how obesity predisposes to sleep apnea. Not all obese subjects have sleep apnea. The focus of this proposal is directed towards understanding the relationship between obesity and obstructive sleep apnea by examining upper airway structure (volumetric magnetic resonance imaging studies) and function (Pcrit and dynamic MRI). Specifically we will: 1) compare 80 weight matched normals to 80 apneics in a case-control study;2) directly examine the effect of weight loss on 60 apneics undergoing surgical weight loss;and 3) examine the effect of weight gain in obese and lean Zucker and Sprague- Dawley rats. This proposal is based on the overall hypotheses that patients with sleep apnea will have more fat in the tongue as compared to weight matched controls;weight loss will decrease tongue fat,increase upper airway caliber and make the airway less collapsible;and weight gain in Zucker rats will increase tongue size and tongue fat.
Our specific aims are: 1) to compare tongue size and adiposity in apneics and obesity-matched controls without apnea in a gender-stratified, case-control design and determine the effects of these tongue properties on airway caliber, airway collapsibility and neuromotor activation of upper airway dilator muscles;2) to examine changes over time in tongue size and adiposity in apneics undergoing surgical weight loss and to determine the effects of changes on tongue properties on airway caliber, AMIand airway collapsibility;and 3) to determine the effect of weight gain on abdominal visceral fat (measured by MRI), tongue fat (measured byMRI and biochemically), tongue volume, and airway size in two rat models of obesity;genetic (Zucker) and genetic-environmental interaction (diet-induced in Sprague-Dawley rats). Our resources, which include advanced MR imaging techniques (including Dixon imaging and MR spectroscopy), novel volumetric computer image analysis paradigms, a robust bariatric surgery program and expertise in sleep apnea biostatistics, rodent imaging studies, polysomnography, and Pcrit will allow us to achieve our specific aims.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL094307-04
Application #
8377420
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$286,872
Indirect Cost
$92,346
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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