Endotypic Traits and Obstructive Sleep Apnea Surgery

Inclusion criteria are:

1. age ≥21 years;
2. moderate to severe OSA (obstructive AHI ≥ 15 events/hour);
3. central/mixed apnea index \<5 events/hour;
4. intolerance of positive airway pressure (defined as use \< 2 hours/night at least 5 nights/week);
5. intolerance or poor candidate for oral appliance;
6. participant has provided informed consent for palate surgery as part of their standard of care;
7. tonsil size 0-2+ (without markedly enlarged tonsils that have high surgical success rates);
8. DISE without evidence of complete tongue-related obstruction (reflecting poorer results with isolated palate surgery);
9. medications stable for ≥2 months;
10. body mass index \<35 kg/m2;
11. absence of uncontrolled nasal obstruction;
12. no prior pharyngeal surgery other than tonsillectomy;
13. no neurologic, cardiac or pulmonary disorders;
14. absence of psychiatric disorder except for treated depression or mild anxiety;
15. no co-existing sleep disorder, such as narcolepsy, chronic insomnia, or restless legs syndrome;
16. no use of hypnotics, anxiolytics, stimulants, or sedating antidepressants;
17. no near-miss or prior motor vehicle crash due to sleepiness in past 12 months; and
18. \<3 caffeinated beverages daily.

Exclusion criteria are:

1. history of allergic reaction to either of the study drugs;
2. subjects with prior serious allergic reaction (such as Stevens-Johnson syndrome) to sulfonamides;
3. subjects with a history of hypersensitivity to either of the two study drugs;
4. subjects who are on high-dose aspirin therapy due to risk of severe metabolic acidosis;
5. subjects with severe kidney disease or severe liver disease;
6. subjects with a history of electrolyte imbalance or adrenal insufficiency (due to risks related to acetazolamide);
7. subjects on ketoconazole or other strong CYP3A4 inhibitors (these will increase eszopiclone blood levels);
8. pregnancy; and
9. alcohol or substance abuse.