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Principal Investigator: ERIC JAMES KEZIRIAN
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2024
Award: $590,974
Funding agency: National Heart Lung and Blood Institute
We propose to conduct a prospective cohort (observational) study of 150 participants with
moderate to severe obstructive sleep apnea (OSA) unable to tolerate positive airway pressure
who are undergoing drug-induced sleep endoscopy (DISE), including measurement of upper
airway closing pressure (Pclose), and tissue-repositioning soft palate surgery. Before and 6
months after surgery, we will measure OSA severity (apnea-hypopnea index) with sleep studies
(polysomnograms). Using our recently-validated polysomnography-based signal processing
algorithm, we will systematically assess the underlying mechanisms of OSA (traits) and airflow
shape (consistent with palate obstruction). The expected 90 participants without resolution of
OSA after surgery (surgery failures) will participate in an experimental randomized crossover
study of acetazolamide (1 month) and acetazolamide/eszopiclone combination (1 month).
Polysomnograms will be performed with each treatment, with algorithm-based determination of
traits. The research goals are: (1) to define how mechanistic traits modify effectiveness of
anatomic treatment (surgery) and (2) to examine the therapeutic efficacy of surgery in
combination with endotype-directed (especially loop gain- and arousal threshold-directed)
treatment. Aim 1: To determine the mechanistic factors modifying the impact of soft
palate surgery on airway collapsibility. Hypothesis: tissue-repositioning palate surgery will
decrease airway collapsibility, with the decrease greater with palate-only obstruction (based on
DISE and non-invasive airflow shape analysis). Aim 2: To evaluate the mechanistic factors
modifying efficacy of soft palate surgery on OSA severity. Hypotheses: surgery efficacy will
be independently associated with palate-only obstruction (DISE) and the following prior to
surgery: lesser airway collapsibility, lesser loop gain, and greater arousal threshold. Aim 3: To
evaluate the efficacy of combining surgery with loop gain and arousal threshold
interventions. Hypotheses: In surgery failures (non-responders), lowering loop gain
(acetazolamide) will lower OSA severity (expected response rate = 40%); efficacy will be
associated with lesser postoperative (prior to medication) airway collapsibility and greater
postoperative loop gain. Lowering loop gain and raising arousal threshold together
(acetazolamide/eszopiclone) will further reduce OSA severity (expected response rate = 60%);
efficacy will be associated with lesser postoperative airway collapsibility and the combination of
greater postoperative loop gain and lesser postoperative arousal threshold.
Terms: <Acetazolamide><Address><Air Movements><Algorithms><Anatomic Sites><Anatomic structures><Anatomy><Apnea><Arousal><Body Tissues><Breathing><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Cross-Over Studies><Crossover Studies><Dilator><Disease><Disorder><Drowsiness><Drugs><Dysfunction><Effectiveness><Endoscopy><Eszopiclone><Evaluation><Failure><Functional disorder><Goals><Heart Vascular><Intervention><Intervention Strategies><Investigation><Measurement><Measures><Medication><Morbidity><Morbidity - disease rate><Multiple Abnormalities><Muscle><Muscle Tissue><Neurocognitive><Obstruction><Obstructive Sleep Apnea><Operative Procedures><Operative Surgical Procedures><Palate><Participant><Patients><Pattern><Pharmaceutical Preparations><Physiopathology><Polysomnography><Position><Positioning Attribute><Post-Operative><Postoperative><Postoperative Period><Procedures><Prospective cohort><Public Health><QOL><Quality of life><Randomized><Research><Resolution><Respiratory Aspiration><Respiratory Inspiration><Sedation procedure><Severities><Shapes><Sleep><Sleep Monitoring><Soft Palate><Somnography><Somnolence><Source><Surgical><Surgical Interventions><Surgical Procedure><Syndrome, Sleep Apnea, Obstructive><Therapeutic><Tissues><Treatment Efficacy><Velum Palatinum><air flow><airflow><airflow limitation><airflow obstruction><airway limitation><airway obstruction><alternative treatment><circulatory system><determine efficacy><drug/agent><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><endoscopic imaging><evaluate efficacy><examine efficacy><experience><improved><indexing><innovate><innovation><innovative><inspiration><intervention efficacy><interventional strategy><mortality><muscular><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><obstructed airflow><obstructed airway><pathophysiology><polysomnographic><positive airway pressure><pressure><randomisation><randomization><randomly assigned><resolutions><respiratory airway obstruction><response><sedation><shape analysis><shape description><signal processing><sleep measurement><sleep polysomnography><sleepiness><success><surgery><surgery outcome><surgical outcome><therapeutic efficacy><therapy efficacy><trait><ventilation>