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
Soans, Rajath E; Lim, Diane C; Keenan, Brendan T et al. (2016) Automated Protein Localization of Blood Brain Barrier Vasculature in Brightfield IHC Images. PLoS One 11:e0148411
Magalang, Ulysses J; Arnardottir, Erna S; Chen, Ning-Hung et al. (2016) Agreement in the Scoring of Respiratory Events Among International Sleep Centers for Home Sleep Testing. J Clin Sleep Med 12:71-7
Li, Qing Yun; Berry, Richard B; Goetting, Mark G et al. (2015) Detection of upper airway status and respiratory events by a current generation positive airway pressure device. Sleep 38:597-605
Bjornsdottir, Erla; Keenan, Brendan T; Eysteinsdottir, Bjorg et al. (2015) Quality of life among untreated sleep apnea patients compared with the general population and changes after treatment with positive airway pressure. J Sleep Res 24:328-38
Lim, Diane C; Brady, Daniel C; Po, Pengse et al. (2015) Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia. J Appl Physiol (1985) 118:544-57
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
Kuna, Samuel T; Shuttleworth, David; Chi, Luqi et al. (2015) Web-Based Access to Positive Airway Pressure Usage with or without an Initial Financial Incentive Improves Treatment Use in Patients with Obstructive Sleep Apnea. Sleep 38:1229-36
Arnardottir, Erna S; Lim, Diane C; Keenan, Brendan T et al. (2015) Effects of obesity on the association between long-term sleep apnea treatment and changes in interleukin-6 levels: the Icelandic Sleep Apnea Cohort. J Sleep Res 24:148-59
Pak, V M; Keenan, B T; Jackson, N et al. (2015) Adhesion molecule increases in sleep apnea: beneficial effect of positive airway pressure and moderation by obesity. Int J Obes (Lond) 39:472-9
Chirinos, Julio A; Gurubhagavatula, Indira; Teff, Karen et al. (2014) CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 370:2265-75

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