New Treatments for Obstructive Sleep Apnea

Educational Objectives

The goal of this program is to improve the use of devices in obstructive sleep apnea. After hearing and assimilating this program, the clinician will be better able to:

1. Use hypoglossal nerve stimulation in OSA.

Summary

Continuous positive airway pressure (CPAP): Cistulli et al (2019) showed that adherence to CPAP was 75% in a sample of 2.6 million patients

Role of musculature: some patients have a robust genioglossus reflex while others do not; not all patients with sleep apnea have obstructive component; if the upper airway muscles could be activated, it might help some patients with OSA; speaker’s group (Eckert et al [2011]) found that while patients with OSA had stronger muscles (measured by protrusion force), their endurance (time to task failure) was significantly lower compared with controls; Sands et al (2014) found that stronger upper airway muscle activity might prevent sleep apnea in some obese individuals; thus, treatments that enhance upper airway muscle function could potentially help some patients transition from sleep apnea to a non-sleep apnea state

Hypoglossal nerve stimulation (HNS): Malhotra et al (2014) showed that HNS could be of benefit in some patients; patients experience progressive reductions in air flow called negative effort dependence; patients with defective operating muscles may respond well to HNS; Schwartz et al (2023) showed positive results of HNS using a randomized controlled trial; the OSPREY study is ongoing; reports from the International Surgical Sleep Society showed that HNS with bilateral HNS (Genio device) reduced OSA severity, and improved quality of life without device-related complications; daytime removable muscle stimulation device (eXciteOSA) provides transoral neuromuscular electrical stimulation for treating sleep-disordered breathing; the device is placed in the mouth for 20 min during the day for 6 wk to exercise the muscles in a reproducible way; Nokes et al (2023) showed benefit of transoral awake neuromuscular stimulation; another observational study showed improvement in 76% of study participants with 20 min of oral stimulation; Baptista et al (2021) showed improvement in snoring in 91% of patients with mild OSA; on average, snoring was reduced by 50.4%; 70% of patients experienced a more than 50% reduction in snoring; adverse effects include excessive salivation, tingling sensation in the tongue, and metallic taste; adverse effects fade; sustained improvement is observed 6 mo after therapy; Nokes et al (2022) performed a mechanistic study on the effect of daytime oral muscle stimulation and found sustained improvements in tongue endurance; the maximum protrusion force remained the same; Abreu et al (2023) compared sham vs daytime neuromuscular electrical stimulation for OSA and showed significant reduction in apnea hypopnea index; muscle activation might worsen snoring in patients with unstable breathing control

Management strategies: CPAP works well for those who tolerate it for other interventions, eg, surfactant, mandibular advancement devices, oxygen; patients with high loop gain or unstable ventilatory control may not respond to stimulation

Pharmacologic management: sedative hypnotics may be useful; management of obesity is beneficial; the clinician may try to prevent complications of OSA, eg, beta blocker to prevent the catecholamine-induced vasoconstriction; glucagon-like peptide-1 receptor agonists with gastric inhibitory peptide are being studied for management of OSA; concurrent management of obesity and OSA is important; study in New England Journal of Medicine (Jastreboff et al [2023]) showed benefit of retatrutide, which is a triple hormone receptor agonist

Analysis: exosomes are tiny particles in circulation; these extracellular vesicles contain microRNAs; exosomes extracted from humans are introduced into cell cultures or mice to assess their impact on endothelial cells; the exosomes are analyzed after treatment with CPAP or another intervention to check improvement in endothelial cell function; another approach is through the microbiome; certain gut bacteria produce a metabolite, trimethylamine N-oxide (TMAO), which has been linked to atherosclerosis; exposure to intermittent hypoxia and hypercapnia resulted in atherosclerosis in mice models; dimethyldimethyl-1-butanol (DMB) blocks TMAO; improvement in atherosclerosis has been noted after DMB therapy

Readings

Abreu AR, Stefanovski D, Patil SP, et al. Neuromuscular electrical stimulation for obstructive sleep apnoea: comparing adherence to active and sham therapy. ERJ Open Res. 2023;9(6):00474-2023. Published 2023 Dec 27. doi:10.1183/23120541.00474-2023; Cistulli PA, Armitstead J, Pepin JL, et al. Short-term CPAP adherence in obstructive sleep apnea: a big data analysis using real world data. Sleep Med. 2019;59:114-116. doi:10.1016/j.sleep.2019.01.004; Eckert DJ, Lo YL, Saboisky JP, et al. Sensorimotor function of the upper-airway muscles and respiratory sensory processing in untreated obstructive sleep apnea. J Appl Physiol (1985). 2011;111(6):1644-1653. doi:10.1152/japplphysiol.00653.2011; Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity - A phase 2 trial. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972; Nokes B, Schmickl CN, Brena R, et al. The impact of daytime transoral neuromuscular stimulation on upper airway physiology - A mechanistic clinical investigation. Physiol Rep. 2022;10(12):e15360. doi:10.14814/phy2.15360; Nokes B, Baptista PM, de Apodaca PMR, et al. Transoral awake state neuromuscular electrical stimulation therapy for mild obstructive sleep apnea. Sleep Breath. 2023;27(2):527-534. doi:10.1007/s11325-022-02644-9; Sands SA, Eckert DJ, Jordan AS, et al. Enhanced upper-airway muscle responsiveness is a distinct feature of overweight/obese individuals without sleep apnea. Am J Respir Crit Care Med. 2014;190(8):930-937. doi:10.1164/rccm.201404-0783OC; Schwartz AR, Jacobowitz O, Eisele DW, et al. Targeted hypoglossal nerve stimulation for patients with obstructive sleep apnea: A randomized clinical trial [published correction appears in JAMA Otolaryngol Head Neck Surg. 2024 Mar 21;:]. JAMA Otolaryngol Head Neck Surg. 2023;149(6):512-520. doi:10.1001/jamaoto.2023.0161.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Malhotra is a consultant for Eli Lilly and Company, LivaNova, and ZOLL Medical. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Malhotra was recorded at the 29th Annual Advances in Diagnosis and Treatment of Sleep Apnea and Snoring, held February 16-17, 2024, in San Francisco, CA, and presented by the University of California, San Francisco. For more information about upcoming CME activities from this presenter, please visit https://sleepapnea.ucsf.edu. Audio Digest thanks the speakers and the University of California, San Francisco for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

OT571402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

More Details - Certification & Accreditation