Endotypic Traits and Obstructive Sleep Apnea Surgery

Inclusion criteria are: age ≥21 years; moderate to severe OSA (obstructive AHI ≥ 15 events/hour); central/mixed apnea index <5 events/hour; intolerance of positive airway pressure (defined as use < 2 hours/night at least 5 nights/week); intolerance or poor candidate for oral appliance; participant has provided informed consent for palate surgery as part of their standard of care; tonsil size 0-2+ (without markedly enlarged tonsils that have high surgical success rates); DISE without evidence of complete tongue-related obstruction (reflecting poorer results with isolated palate surgery); medications stable for ≥2 months; body mass index <35 kg/m2; absence of uncontrolled nasal obstruction; no prior pharyngeal surgery other than tonsillectomy; no neurologic, cardiac or pulmonary disorders; absence of psychiatric disorder except for treated depression or mild anxiety; no co-existing sleep disorder, such as narcolepsy, chronic insomnia, or restless legs syndrome; no use of hypnotics, anxiolytics, stimulants, or sedating antidepressants; no near-miss or prior motor vehicle crash due to sleepiness in past 12 months; and <3 caffeinated beverages daily. Exclusion criteria are: history of allergic reaction to either of the study drugs; subjects with prior serious allergic reaction (such as Stevens-Johnson syndrome) to sulfonamides; subjects with a history of hypersensitivity to either of the two study drugs; subjects who are on high-dose aspirin therapy due to risk of severe metabolic acidosis; subjects with severe kidney disease or severe liver disease; subjects with a history of electrolyte imbalance or adrenal insufficiency (due to risks related to acetazolamide); subjects on ketoconazole or other strong CYP3A4 inhibitors (these will increase eszopiclone blood levels); pregnancy; and alcohol or substance abuse.