The focus of this proposal is directed towards understanding the biomechanical basis for obstructive sleep apnea and determining the mechanisms underlying the efficacy of therapeutic interventions for this common disorder. We will utilize novel implementations of state-of-the art dynamic magnetic resonance imaging and tagging techniques coupled with physiologic monitoring of respiration during wakefulness and sleep to evaluate the effects of weight loss, mandibular repositioning devices, uvulopalatopharyngoplasty, and maxillomandibular advancement on upper airway structure and function in patients with sleep apnea. The studies proposed will elucidate the biomechanical behavior of the upper airway, and in particular identify the anatomic structures whose motion underlies the dimensional changes which take place in the upper airway during respiration, as well as those structures responsible for airway closure during sleep. We have planned a logical series of studies that will test our overall hypothesis that the critical control structures in sleep apnea are the lateral pharyngeal walls and that the beneficial effects of weight loss and the other therapeutic interventions to treat patients with obstructive sleep apnea will be mediated through their effects on the biomechanical properties of these lateral walls. We have developed high-speed magnetic resonance tagging techniques that will provide a novel method for direct visualization and quantitation of the dynamic motion and deformations of upper airway soft tissues during normal breathing, airway closure and re-opening associated with obstructive apneic events. Regional compliance of the airway and surrounding soft tissues will be measured. Customized computer graphics-based volumetric image analysis and display methods provide for objective quantitation of the image data. The studies proposed, by evaluating dynamic changes in upper anatomy, compliance, regional deformations, and biomechanical functioning of the upper airway soft tissue structures, in conjunction with image-linked physiologic monitoring, will provide insight into the pathogenesis of obstructive sleep apnea and the biomechanical mechanisms underlying the effectiveness of weight loss, dental appliances, and upper airway surgery. Moreover, the knowledge gained from these studies may improve our ability to identify appropriate candidates for the various therapeutic interventions, reduce treatment failures, and lead to new or improved approaches to treating this disorder.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057843-03
Application #
2901283
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1997-07-15
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Schwab, Richard J; Pasirstein, Michael; Kaplan, Laura et al. (2006) Family aggregation of upper airway soft tissue structures in normal subjects and patients with sleep apnea. Am J Respir Crit Care Med 173:453-63
Schwab, Richard J (2005) Genetic determinants of upper airway structures that predispose to obstructive sleep apnea. Respir Physiol Neurobiol 147:289-98
Welch, Kevin C; Foster, Gary D; Ritter, Christen T et al. (2002) A novel volumetric magnetic resonance imaging paradigm to study upper airway anatomy. Sleep 25:532-42
Ritter, C T; Trudo, F J; Goldberg, A N et al. (1999) Quantitative evaluation of the upper airway during nasopharyngoscopy with the Muller maneuver. Laryngoscope 109:954-63