Assessment of Sleep Apnea and Its Causes Before and After Weight Loss Surgery

Sleep Apnea, Obstructive Clinical Trial

Official title: Understanding the Role Obesity Plays in the Pathogenesis of Obstructive Sleep Apnea

Status Terminated

Clinical Trial Summary

The central aim of this research project is to determine how the ever-growing problem of obesity in the western world contributes to the pathophysiology of obstructive sleep apnea (OSA). To complete this aim, the investigators will determine the impact of obesity on the mechanisms underlying OSA. This will be achieved by making physiological measurements of 4 physiological traits known to cause OSA as well as the patients sleep apnea severity, before and after weight-loss surgery (i.e. bariatric surgery).

Clinical Trial Description

Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and cause intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such processes disturb normal sleep and impair neurocognitive function, often resulting in excessive daytime sleepiness and decreased quality of life. Furthermore, OSA is associated with cardiovascular morbidity and mortality, making OSA a major health concern. Obesity is categorically the major risk factor for OSA, with available data indicating a prevalence of 40% in obese men (BMI > 30kg/m2) and up to 90% in morbidly obese individuals (BMI > 40kg/m2). Given the prevalence of obesity has risen to epidemic proportions, with approximately 60% of adults considered overweight and 30% obese, it has become one of the world's leading health care concerns and research priorities. Importantly, as the prevalence of obesity continues to rise, so too does the number of individuals developing OSA. Surprisingly, despite the dominant role played by obesity in OSA pathogenesis, the precise mechanisms by which obesity leads to OSA are unclear

Current evidence suggests that OSA pathogenesis involves the interactions of at least four physiological traits comprising 1) the pharyngeal anatomy and its propensity towards collapse 2) the ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation), 3) the arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep) and 4) the stability of ventilatory feedback loop (i.e. loop gain). The potential mechanisms by which obesity may alter the four traits has to date not been carefully assessed. Specifically, obesity has been suggested to a) compromise the anatomy by decreasing the airway size and increasing its collapsibility, but it may also b) impair neuromuscular compensation by increasing the mechanical load placed on the upper airway muscles, c) increase the loop gain and destabilize breathing potentially via reductions in lung volume and increased chemosensitivity or d) increase the arousal threshold and thereby reduce the propensity to arouse from sleep which may offset some of the obesity-related deficits in the other traits. However, we do not know how obesity alters these four traits (in the same individual) and whether it involves predominantly one or several of the mechanistic pathways.

Therefore the aim of our study is to determine the impact of obesity on the mechanisms underlying OSA. This will be achieved by making physiological measurements before and after weight-loss surgery (i.e. bariatric surgery). Specifically we will assess:

1. The severity of OSA (apnea-hypopnea-index or AHI)

2. The physiological traits responsible for OSA:

i. Pharyngeal anatomy and its propensity towards collapse

ii. The ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation).

iii. Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep).

iv. Stability of ventilatory feedback loop (i.e. loop gain). ;

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

• NCT number: NCT01712269
• Study type: Interventional
• Source: Brigham and Women's Hospital
• Status: Terminated
• Phase: N/A
• Start date: October 2012
• Completion date: January 2017