ABSTRACT
Background Hypoglossal nerve stimulation (HGNS) is an established surgical therapy for obstructive sleep apnea (OSA), yet treatment response is variable and appears to be influenced by both body mass index (BMI) and pattern of upper airway collapse. Whether excess body weight differentially affects HGNS efficacy across pharyngeal collapse patterns remains unclear.
Methods We combined data from two independent HGNS cohorts (n=760) to examine whether the association between BMI and HGNS efficacy depends on pharyngeal collapse pattern identified by drug-induced sleep endoscopy. Collapse was categorized as predominantly laterally directed or anteroposterior (AP). Multivariable regression models assessed HGNS efficacy—quantified primarily as percent reduction in apnea–hypopnea index (AHI) on titration polysomnography and secondarily as treatment success (≥50% AHI reduction to <15 events/h)—while testing for effect modification by collapse pattern and adjusting for baseline AHI, partial collapse, surgical center, follow-up sleep study type, and prior or concomitant pharyngeal surgery.
Results Increasing BMI was associated with substantially lower HGNS efficacy among patients with laterally directed collapse, whereas the relationship between BMI and efficacy was attenuated in those with AP collapse. Specifically, each 5 kg/m² increase in BMI was associated with a −19.7% (95% CI: −33.2 to −6.2) greater reduction in efficacy in lateral collapse compared with −3.8% (−8.0 to 0.36) in AP collapse (interaction p=0.027). Higher BMI also corresponded to reduced odds of treatment success in lateral collapse (odds ratio 4.4 [95% CI: 1.4–14.3] per 5 kg/m²), with no significant association observed in AP collapse (1.1 [0.75–1.5]; interaction p=0.023).
Conclusions The influence of BMI on HGNS treatment response differs meaningfully by pharyngeal collapse phenotype. Incorporating collapse pattern into BMI-based eligibility criteria may improve patient selection and optimize HGNS outcomes.
Competing Interest Statement
DV receives personal fees as a consultant and grant funding from Inspire Medical Systems. EJK serves as a consultant for Cryosa, Nyxoah, and Berendo Scientific. EJK is a co-inventor related to intellectual property for Magnap and Berendo Scientific. EJK has previously received research funding from Inspire Medical Systems. AA reports grant support from Somnifix and serves as a consultant for Respicardia, Eli Lilly, Inspire, Cerebra, and Apnimed. Apnimed is developing pharmacological treatments for obstructive sleep apnea. AAs interests were reviewed by Brigham and Womens Hospital and Mass General Brigham in accordance with institutional policies. AW serves as a consultant for Apnimed, Nox, Inspire, Mosanna, Takeda, and iNOS. AW has received grants from Prosomnus. AW has a financial interest in Apnimed, Mosanna, and iNOS, which are developing therapies for sleep apnea. AWs interests were reviewed and are managed by Brigham and Womens Hospital and Mass General Brigham in accordance with conflict of interest policies. DK has received research support from Inspire Medical Systems Inc and Invicta Medical Inc. DK serves as a consultant for Invicta Medical Inc and is a scientific advisory board member for Nyxoah SA. DK also holds intellectual property interests and has received research support from Nyxoah SA. DPW serves as a consultant for Apnimed, Philips, Nidra, Mosanna, Onera, Bairiton, Xtrodes, Cerebra Health, Cryosa, Resonea, and SleepRes. SS has received grant support from Apnimed, Prosomnus, and Dynaflex and has served as a consultant for Apnimed, Nox Medical, Inspire Medical Systems, Eli Lilly, Respicardia, LinguaFlex, and Achaemenid. SS receives royalties for intellectual property pertaining to combination pharmacotherapy for sleep apnea through his institution. SS is also a co-inventor of intellectual property pertaining to wearable sleep apnea phenotyping through his institution. SS has received equity in Achaemenid, a company commercializing biosensor technology for monitoring oral appliance treatment efficacy. SSs industry interactions are actively managed by his institution. PH serves as an educational consultant for Inspire Medical Systems and receives research support from Inspire Medical Systems and Nyxoah. The funders were not involved in the study design, data collection, data analysis, manuscript preparation, or the decision to submit the article for publication.
Funding Statement
Daniel V. Vena was supported by grants from the American Heart Association (Grant No. 938014) and the American Academy of Sleep Medicine (Grant No. 257-FP-21). Eric J. Kezirian was supported by a grant from the National Institutes of Health (HL160993). Andrew Wellman reports grant support from the National Institutes of Health (HL102321 and HL128658). Scott A. Sands was supported by the American Thoracic Society (15SDG25890059) and the National Institutes of Health, National Heart, Lung, and Blood Institute (R01HL146697).
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This study was approved by the Institutional Review Board of Mass General Brigham, and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants or was waived by the IRB, as applicable.
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Footnotes
The abstract was revised to improve clarity and precision of language. No new data, analyses, or conclusions were added.
Data Availability
The data supporting the findings of this study are not publicly available due to privacy and regulatory restrictions, but are available from the corresponding author upon reasonable request and with appropriate institutional approvals.
