# Upper airway collapsibility, loop gain and arousal threshold: an integrative therapeutic approach to obstructive sleep apnea

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $635,693

## Abstract

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.

## Key facts

- **NIH application ID:** 10859275
- **Project number:** 7R01HL160993-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ERIC JAMES KEZIRIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $635,693
- **Award type:** 7
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859275

## Citation

> US National Institutes of Health, RePORTER application 10859275, Upper airway collapsibility, loop gain and arousal threshold: an integrative therapeutic approach to obstructive sleep apnea (7R01HL160993-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10859275. Licensed CC0.

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