Obstructive sleep apnea is a major problem in the elderly due to its high prevalence and its well recognized neurocognitive and cardiovascular complications. Afflicted individuals have substantial daytime symptoms including fatigue, malaise, sleepiness and reduced quality of life. Despite this, minimal research has been performed to investigate the mechanisms underlying the development of this disease with aging. Current theory suggests that sleep apnea pathogenesis involves a complex interactions of anatomical variables, protective reflex mechanisms, ventilatory control abnormalities among others. The principal investigator proposes to extend the observations from his Beeson award to pursue more comprehensive evaluations of the critical variables using a new patient population in both sleep and wakefulness. During the proposed granting period, we will investigate the normal effects of aging on a number of mechanistic variables of interest and further we will define the impact of sleep apnea disease on these parameters. Based on our preliminary data, the groups of variables will likely form phenotypic clusters whereby a certain abnormality (or group of abnormalities) either causes disease (or protects from disease) in older and younger individuals. This protocol will allow us to test a number of hypotheses regarding potential mechanisms underlying sleep apnea using state-of-the-art technology and methods. We have developed a conceptual framework whereby we can classify patients into OSA or control based on their underlying pathophysiology with a view towards understand why a given patient does or does not have sleep apnea. Ultimately our goal is to identify new therapeutic targets for sleep apnea in the elderly since the current therapies are often poorly tolerated in this and other age groups.

Public Health Relevance

Sleep apnea is a major problem for the elderly because it is very common and leads to marked reductions in quality of life. Treatments for sleep apnea are often poorly tolerated by older individuals and therefore research into underlying mechanisms is very important in order for new treatments to be developed. We plan to characterize many of the variables important in causing sleep apnea so that we can develop a better understanding of why the elderly develop this disease, and how best to prevent or minimize its complications.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL090897-04
Application #
8299434
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Twery, Michael
Project Start
2009-07-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$441,788
Indirect Cost
$194,288
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
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
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
McSharry, David G; Saboisky, Julian P; Deyoung, Pam et al. (2014) Physiological mechanisms of upper airway hypotonia during REM sleep. Sleep 37:561-9
Shah, Ravi V; Abbasi, Siddique A; Heydari, Bobak et al. (2014) Obesity and sleep apnea are independently associated with adverse left ventricular remodeling and clinical outcome in patients with atrial fibrillation and preserved ventricular function. Am Heart J 167:620-6
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
Bakker, Jessie P; Edwards, Bradley A; Gautam, Shiva P et al. (2014) Blood pressure improvement with continuous positive airway pressure is independent of obstructive sleep apnea severity. J Clin Sleep Med 10:365-9
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
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
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

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