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

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).

Inclusion Criteria:

- Ages 18 - 65 years

- BMI > 35kg/m2

- Scheduled for weight-loss surgery

Exclusion Criteria:

- Previous history of bariatric surgery

- Any serious medical condition (except controlled hypertension and diabetes)

- Any sleep disorder except OSA (RLS, insomnia, etc.)

- Use of medications known to affect sleep/arousal, breathing, or muscle physiology

- Allergy to lidocaine or Afrin

- History of current cigarette smoking or previous smoking history >10 pack years