Obstructive sleep apnea (OSA) is a common disease with major cardiovascular and neurocognitive consequences and yet current therapies are unacceptable for some patients. While CPAP (continuous positive airway pressure) can be transformative for some patients, adherence to this treatment is highly variable and alternative therapies suffer from incomplete efficacy. We have recently observed evidence of neuromyopathy in OSA using some newly developed sophisticated electrophysiological techniques. These data have corroborated the findings of other groups showing either sensory or motor impairment of upper airway neuromuscular reflexes in OSA. However, we remain unclear whether the observed findings are indeed clinically important. We plan to define the variability in reinnervation (a marker of nerve injury) in OSA compared to matched controls, also trying to identify predictors of this pattern for clinicians to use. We will further assess the importance of these findings by assessing tongue protrusion force and fatigability as well as the potential impact of neuromyopathy on upper airway mechanics during sleep. We will also conduct a pilot clinical trial to assess the impact of muscle training exercises on OSA patients with and without evidence of reinnervation. Ultimately, we hope that our research will help to define new therapeutic targets at least for a subset of OSA patients.

Public Health Relevance

Statement Sleep apnea patients sometimes have serious complications. Recent evidence suggests that the nerves and muscles controlling the upper airway may be damaged in sleep apnea patients. We will determine how common this problem is, how it affects the function of the airway muscles during wakefulness and sleep and whether it can be treated effectively with muscle training exercises.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01HL085188-05A1
Application #
8698091
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Laposky, Aaron D
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Darquenne, Chantal; Hicks, Charles B; Malhotra, Atul (2015) The ongoing need for good physiological investigation: obstructive sleep apnea in HIV patients as a paradigm. J Appl Physiol (1985) 118:244-6
Owens, Robert L; Edwards, Bradley A; Sands, Scott A et al. (2014) The classical Starling resistor model often does not predict inspiratory airflow patterns in the human upper airway. J Appl Physiol (1985) 116:1105-12
Edwards, Bradley A; Wellman, Andrew; Sands, Scott A et al. (2014) Obstructive sleep apnea in older adults is a distinctly different physiological phenotype. Sleep 37:1227-36
Sarge, Todd; Loring, Stephen H; Yitsak-Sade, Maayan et al. (2014) Raising positive end-expiratory pressures in ARDS to achieve a positive transpulmonary pressure does not cause hemodynamic compromise. Intensive Care Med 40:126-8
Bakker, Jessie P; Campana, Lisa M; Montesi, Sydney B et al. (2014) A pilot study investigating the effects of continuous positive airway pressure treatment and weight-loss surgery on autonomic activity in obese obstructive sleep apnea patients. J Electrocardiol 47:364-73
Eckert, Danny J; White, David P; Jordan, Amy S et al. (2014) Reply: Arousal threshold in obstructive sleep apnea. Am J Respir Crit Care Med 189:373-4
Djonlagic, Ina; Guo, Mengshuang; Matteis, Paul et al. (2014) Untreated sleep-disordered breathing: links to aging-related decline in sleep-dependent memory consolidation. PLoS One 9:e85918
Kezirian, Eric J; Goding Jr, George S; Malhotra, Atul et al. (2014) Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes. J Sleep Res 23:77-83
Jordan, Amy S; McSharry, David G; Malhotra, Atul (2014) Adult obstructive sleep apnoea. Lancet 383:736-47
Eckert, Danny J; Malhotra, Atul; Wellman, Andrew et al. (2014) Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep 37:811-9

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