Obstructive sleep apnea (OSA) is a common, debilitating disorder characterized by recurrent collapse of the pharyngeal airway during sleep. This leads to both sleep fragmentation as arousal is required to terminate these events and the sequelae of recurrent hypoxia and hypercapnia. Thus, afflicted individuals are somnolent during the day due to sleep fragmentation and may be at increased risk for hypertension, myocardial infarction or stroke. Our current understanding of the pathophysiology of this disorder is incomplete but suggests that reduced pharyngeal airway size in concert with sleep-induced changes in pharyngeal dilator muscle activation lead to airway collapse during sleep. Our current protocols have three specific goals: 1. Neural Control of Pharyngeal Muscle Activation - We hope to better define the mechanisms controlling upper airway muscle activity awake and asleep using novel approaches which allow up to precisely control airway pressure and flow as we examine the EMG of two pharyngeal muscles. 2. Testosterone and Apnea Pathogenesis: Sleep apnea is well known to be more common in men than women, although the mechanistic explanation for this observation remains unclear. We have designed a series of studies to carefully examine the effects of testosterone on pharyngeal muscle activity, airway anatomy (MRI) and ventilatory stability (loop gain) in several populations in whom testosterone levels can be manipulated relatively easily. 3. Obesity and Apnea Pathogenesis: As with male gender, obesity is a very common trait in sleep apnea. However, the mechanism by which obesity leads to airway obstruction during sleep remains unresolved. We, therefore, plan to assess the impact of surgically-induced weight loss not only on sleep apnea severity but on pharyngeal muscle activation and control, upper airway anatomy (MRI/CT), and ventilatory control stability (loop gain). The latter two protocols should not only improve our understanding of the mechanisms influencing apnea epidemiology, but also allow us to begin to build multi-variant predictive models of apnea pathogenesis incorporating the three relevant variables (anatomy, airway motor control and respiratory control stability). This should substantially improve our understanding of this disorder.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL048531-10
Application #
6537038
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Twery, Michael
Project Start
1992-07-20
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
10
Fiscal Year
2002
Total Cost
$423,750
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Sands, Scott A; Terrill, Philip I; Edwards, Bradley A et al. (2018) Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea. Sleep 41:
Sands, Scott A; Mebrate, Yoseph; Edwards, Bradley A et al. (2017) Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure. Am J Respir Crit Care Med 195:237-246
Cori, Jennifer M; Thornton, Therese; O'Donoghue, Fergal J et al. (2017) Arousal-Induced Hypocapnia Does Not Reduce Genioglossus Activity in Obstructive Sleep Apnea. Sleep 40:
Nguyen, Chinh D; Wellman, Andrew; Jordan, Amy S et al. (2016) Mild Airflow Limitation during N2 Sleep Increases K-complex Frequency and Slows Electroencephalographic Activity. Sleep 39:541-50
Carberry, Jayne C; Jordan, Amy S; White, David P et al. (2016) Upper Airway Collapsibility (Pcrit) and Pharyngeal Dilator Muscle Activity are Sleep Stage Dependent. Sleep 39:511-21
Amatoury, Jason; Azarbarzin, Ali; Younes, Magdy et al. (2016) Arousal Intensity is a Distinct Pathophysiological Trait in Obstructive Sleep Apnea. Sleep 39:2091-2100
Owens, Robert L; Edwards, Bradley A; Eckert, Danny J et al. (2015) An Integrative Model of Physiological Traits Can be Used to Predict Obstructive Sleep Apnea and Response to Non Positive Airway Pressure Therapy. Sleep 38:961-70
Terrill, Philip I; Edwards, Bradley A; Nemati, Shamim et al. (2015) Quantifying the ventilatory control contribution to sleep apnoea using polysomnography. Eur Respir J 45:408-18
Edwards, Bradley A; Eckert, Danny J; McSharry, David G et al. (2014) Clinical predictors of the respiratory arousal threshold in patients with obstructive sleep apnea. Am J Respir Crit Care Med 190:1293-300
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

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