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

Award Number: R01HL160993
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $590,974 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center on Sleep Disorders Research	003	3	9/6/2024	NON-COMPETING CONTINUATION	$590,974
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center on Sleep Disorders Research	000	2	11/10/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center on Sleep Disorders Research	002	2	1/19/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$737,841
2024	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	National Center on Sleep Disorders Research	001	1	1/19/2024	NEW	-$737,841
														Subtotal = $590,974

Issue Date FY: 2023 ( Subtotal = $635,693 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center on Sleep Disorders Research	001	2	9/1/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$635,693
2023	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	National Center on Sleep Disorders Research	000	1	8/31/2023	NEW	$0
														Subtotal = $635,693

Issue Date FY: 2022 ( Subtotal = $737,841 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	National Center on Sleep Disorders Research	000	1	8/5/2022	NEW	$737,841
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	National Center on Sleep Disorders Research	001	1	9/26/2022	NEW	$0
														Subtotal = $737,841

Grand Total All Awards = $1,964,508

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

Award Number: R01HL160993

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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