Dr. Naomi Deacon
Recent studies suggest that sleep apnea occurs for varying reasons, a concept that is now thought to be clinically important (Jordan et al. Lancet. 2014;383[9918]:736). We draw a crucial distinction between endotypes (mechanisms underlying disease) and phenotypes (clinical expression of disease). Important endotypes include compromised upper airway anatomy, dysfunction in pharyngeal dilator muscles, unstable ventilatory control (high loop gain), and low arousal threshold (wake up easily), among others. Important phenotypes of sleep apnea are emerging and still evolving to include minimally symptomatic OSA, OSA with daytime sleepiness, and OSA with major cardiometabolic risk, among others. Several important concepts have emerged regarding different OSA endotypes and phenotypes:
1 The mechanism underlying OSA may predict potential response to therapeutic interventions. For instance, the endotype of OSA with unstable ventilatory control (high loop gain) may respond to agents such as oxygen and acetazolamide, which serve to stabilize control of breathing. In patients with anatomical compromise at the level of the velopharynx, uvulopalatopharyngoplasty may be an effective intervention. For patients with multiple pathophysiologic abnormalities, combination therapy may be required to alleviate OSA (Edwards et al. Sleep. 2016;9[11]:1973).
2 Given that OSA has many underlying etiologies, efforts are underway to determine whether individuals with different risk factors for OSA develop their disease based on varying mechanisms. As an example, people with posttraumatic stress disorder (PTSD) may be at increased risk of OSA perhaps on the basis of a low threshold for arousal (Orr et al. JCSM. 2017, 13[1]: 57-63). Another example would be patients with neuromuscular disease who may be at risk of OSA primarily based on impaired pharyngeal dilator muscle function.