XRead - Summary and Articles 1

Adult Sleep Apnea
April 2022
AAO‐HNSF General Otolaryngology & Sleep Education Committee
Faculty
Valerie A. Flanary, MD
Sveta A. Karelsky, MD
Benjamin D. Malkin, MD
Lara K. Reichert, MD, MPH
Jeffrey J. Stanley, MD
This activity provides five scientific journal articles with expert summaries designed to provide relevant and timely
clinical information for physicians in training and current practitioners in otolaryngology – head and neck surgery.
© Copyright 2022. AAO‐HNSF FLEX xRead: April 2022 1|P a g e

Article 1
Handler E, Hamans E, Goldberg AN, Mickelson S. Tongue suspension: An evidence‐based review and comparison
to hypopharyngeal surgery for OSA. Laryngoscope. 2014 Jan; 124(1):329‐36.
EBM Level: 4 – Systematic Review
Summary: The authors perform a systemic review of 27 studies to compare tongue suspension, tongue suspension
with uvulopalatopharyngoplasty (UPPP), genioglossus advancement (GA) with UPPP, and GA with hyoid suspension
myotomy (GAHM) and UPPP. Surgical success of tongue suspension alone was 36.6%. Chi‐squared analysis showed
no difference between surgical outcomes of tongue suspension + UPPP, GA + UPPP, and GAHM + UPPP, with
success rates of 61‐62%. Surgeons should consider tongue suspension among options for surgical management of
hypopharyngeal obstruction.
Article 2
Huyett P, Kent D, D’Agostino M, et al. Drug‐Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation
Outcomes: A Multicenter Cohort Study. Laryngoscope. 2021 July; 131(7): 1676–1682.
EBM Level: 3
Summary: This is a retrospective multicenter study of 343 adults with OSA who underwent drug induced sleep
endoscopy (DISE) and treatment with hypoglossal nerve stimulation (HNS). The purpose is to examine associations
between DISE findings and outcomes of HNS treatment. DISE scoring took place by four blinded reviewers and HNS
treatment outcomes were evaluated with titration PSG and treatment HSAT. The study found that contribution to
obstruction primarily by the tongue was associated with better outcomes, whereas obstruction by the lateral
pharyngeal walls was associated with worse outcomes in patients with higher BMI. The study also challenges the
notion that patients with complete circumferential obstruction at the velum do not benefit from HNS treatment.
The study provides more detailed information as to which patients may benefit most from HNS than has generally
been available to date.

Article 3
Kent D, Stanley J, Aurora, R, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an
American Academy of Sleep Medicine clinical practice guideline. Journal of Clinical Sleep Medicine. 2021; 17(12):
2499‐2505.
EBM Level: 4 – Systematic Review
Summary: Although positive airway pressure (PAP) is a highly efficacious treatment for obstructive sleep apnea
(OSA), a portion of patients are unable to tolerate it, compromising the potential subjective and objective benefits.
A discussion with patients regarding referral for surgical consultation in this situation is recommended.
Upper airway surgery is a viable rescue therapy for many PAP‐intolerant patients. Structural surgeries are designed
to reduce upper airway collapsibility and have demonstrated substantial improvements in patient‐centered
outcomes including excessive daytime sleepiness, sleep specific quality of life and snoring. Improvements in
objectives measures of disease severity include a reduction in Apnea Hypopnea Index (AHI), Oxygen Desaturation
Index (ODI) and a reduction in systolic and diastolic blood pressure. Upper airway stimulation via implantation of a
hypoglossal nerve stimulator has also been shown to achieve significant improvements in daytime sleepiness,
quality of life and AHI. Upper airway surgery has also been utilized as an adjunctive treatment to facilitate the use
of PAP. Surgeries targeting the nose, tonsils and soft palate have demonstrated clinically significant reductions in
therapeutic PAP requirements as well as significant increases in PAP adherence. Bariatric surgery has also been
shown to improve objective measures of OSA and to reduce therapeutic PAP requirements.
Article 4
MacKay S et al. Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea‐Hypopnea
Index and Patient‐Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep
Apnea: The SAMS Randomized Clinical Trial. JAMA 2020;324(12):1168‐1179.
EBM Level: 2 – Randomized Trial
Summary: The authors present the results of a randomized trial of 102 adults with moderate or severe OSA,
BMI<38, Friedman sleep stage I‐III, in whom prior attempts at conventional medical device treatment had failed;
multilevel sleep surgery was compared with ongoing medical management. Surgery significantly improved the AHI
and patient‐reported sleepiness at 6 months. It was also associated with improvements in most other
polysomnography measures (arterial oxygen saturation measures and cortical arousal frequency), partner‐reported
snoring and patient‐reported sleep‐specific quality of life and general health status. Mean sleep latency and blood
pressure values were in the normal range and were unchanged at 6 months. There were six serious adverse events
in four participants in the surgery group and no serious adverse events in the ongoing medical management group.

Article 5
Suurna M, Steffen A, Boon M, Chio E, et al. Impact of Body Mass Index and Discomfort on Upper Airway
Stimulation: ADHERE Registry 2020 Update. Laryngoscope. 2021 Nov; 131:2616‐2624.
EBM Level: 4
Summary: ADHERE registry update, similar to previous study, shows a significant decrease in AHI and normalization
of the ESS. Patients with discomfort had higher AHI and lower therapy use but no significant difference in ESS. Most
patients used UAS a monotherapy. Patients with BMI greater than 35 had lower likelihood of meeting Sher surgical
success criteria. UAS is an effective second line therapy for greater than 32 BMI in moderate to severe OSA. Reports
of adverse effects were low. Discomfort did decrease time of device use and less decrease in AHI. Addressing pain
early on is important for long term adherence.

The Laryngoscope
C 2013 The American Laryngological,
V
Rhinological and Otological Society, Inc.
Tongue Suspension: An Evidence-Based Review and Comparison to

Hypopharyngeal Surgery for OSA
Ethan Handler, MD; Evert Hamans, MD, PhD; Andrew N. Goldberg, MD, MSCE; Samuel Mickelson, MD
Objectives/Hypothesis: Our first objective was to perform a systematic review of suture-based tongue suspension pro-
cedures as a stand-alone therapy for hypopharyngeal obstruction in obstructive sleep apnea (OSA). A second objective com-
pared outcomes of tongue suspension as part of a multilevel approach to OSA surgery to genioglossus advancement (GA)
with uvulopalatopharyngoplasty (UPPP), and to genioglossus advancement with hyoid suspension (GAHM) with UPPP.
Study Design: Systematic review.
Methods: The PubMed database was queried for English-language studies published after 1997 to create four cohorts:
tongue suspension alone, tongue suspension with UPPP, GA 1 UPPP, and GAHM with UPPP. Chi-squared test was used to com-
pare outcomes between cohorts.
Results: Twenty-seven studies were included, broken down into cohorts based on our selection criteria. Six studies
qualified for the tongue suspension-alone group with a surgical success rate of 36.6%. Eight studies qualified for our cohort
of tongue suspension with UPPP with a surgical success rate of 62.3%. Eighteen studies qualified for our remaining two
cohorts: GA 1 UPPP, and GAHM 1 UPPP. Their surgical success rates were both 61.1%. A chi-squared test to compare surgical
outcomes showed that there was no difference between tongue suspension with UPPP, GA 1 UPPP, and GAHM 1 UPPP.
Conclusion: Tongue suspension is effective and safe as part of a multilevel surgical approach for patients with OSA. As
a stand-alone procedure, its success rate is 36.6%, comparable to UPPP procedures for OSA success rates across the board.
Tongue suspension should be considered in patients with OSA who demonstrate tongue base obstruction.
Key Words: Tongue suspension, OSA, hypopharyngeal, multilevel surgery, genioglossus advancement, hyoid suspension.
Level of Evidence: 4.
Laryngoscope, 124:329–336, 2014
INTRODUCTION Continuous positive airway pressure (CPAP) is cur-

Obstructive sleep apnea (OSA) is a disorder of sleep rently considered the first-line treatment for OSA. It has
characterized by partial or complete collapse of the shown to improve symptoms, normalize the risk of traf-
upper airway.1 This occurs secondary to inadequate tone fic and work accidents, normalize mortality in
of the tongue and/or dilator muscles of the upper airway. severe OSA, and reduce the risk of cardiovascular inci-
In the United States, the prevalence of OSA is approxi- dents.10–12 Aside from tracheotomy, a CPAP device
mately 2% to 5% in women and 3% to 7% in men.2 The serves as the best therapy to treat OSA, yet outcomes
sequelae of untreated OSA have been well documented. are strictly tied to compliance. Discomfort of the mask
Multiple studies have linked conditions including and feelings of suffocation, noise, and discomfort of the
hypertension, cerebrovascular accident, neurocognitive apparatus are a few reasons that patients abandon the
impairment, motor vehicle accidents, abdominal aortic device. Short- and long-term compliance of CPAP has
aneurysm enlargement, and insulin resistance to been estimated between 40% to 80% as patients often
untreated OSA.2–9 seek surgical intervention, oral appliances, or never
commence CPAP treatment after obtaining the device.13–
15
In a recent study, Stuck et al. found that in an ideal
From the Department of Head and Neck Surgery (E.HANDLER), Kai-
group of CPAP-compliant patients, the mean AHI under
ser Permanente, Oakland, California, U.S.A.; the Department of Otorhi- treatment was still above 10.16
nolaryngology, Head and Neck Surgery (E.HAMANS), Multidisciplinary Obstructive sleep apnea is a multilevel disease;
Sleep Center, University Hospital Antwerp, Edegem, Belgium; the San
Francisco, Department of Otolaryngology–Head and Neck Surgery thus, determining the anatomical and physiological site
(A.N.G.), University of California, San Francisco, California; and the of obstruction is critical for matching a patient to the
Advanced Ear, Nose & Throat Specialists (S.M.), PC, Atlanta, Georgia,
U.S.A.
appropriate surgical intervention(s). Various systems
Editor’s Note: This Manuscript was accepted for publication April have been suggested to better categorize the level of
15, 2013. obstruction, including the Fujita classification, Friedman
Disclosures: Philips (E.HAMANS); ApniCure (A.N.G.); Siesta Medical staging, and more recently, drug-induced sleep endos-
(E.HANDLER, A.N.G., S.M.). The authors have no other funding, financial
relationships, or conflicts of interest to disclose.
copy (DISE).17–19 In his 10-year retrospective audit,
Send correspondence to Ethan B. Handler, MD, Kaiser Perma- Kotecha et al.20 first documented the efficacy of DISE
nente–Department of Head and Neck Surgery, Oakland, California, with regard to diagnosing the appropriate level of
94105. E-mail: [email protected]
obstruction and found that surgical outcomes correlated
DOI: 10.1002/lary.24187 well with findings from sleep endoscopy. Currently, the
Laryngoscope 124: January 2014 Handler et al.: EBM Review of Tongue Suspension for OSA
329
TABLE I. The clinical indication was unrelated to OSA and/or snoring.
Hierarchy From Oxford Center for Evidence-Based Medicine. The language was not in English.
The article was published before 1998.
Level of Evidence Study Design
The second search was used to identify tongue suspension
1 Randomized, controlled trial
procedures as part of a multilevel approach to treat OSA. A
2 Cohort study PubMed search for “tongue suspension” was performed in Octo-
3 Case-control study ber 2012, resulting in 195 potential articles. Articles were
4 Case series excluded from this pool for the following reasons:
5 Expert opinion The publication was a letter or comment.
A tongue suspension procedure was not performed as part of
the methods.
consensus is that patients with hypopharyngeal obstruc- The procedure was performed without UPPP.
tion in addition to retropalatal obstruction are unlikely The clinical indication was unrelated to OSA and/or snoring.
to be improved by retropalatal surgery alone. Further- The language was not in English.
more, the practice of a patient-specific operative The article was published before 1998.
approach to level of obstruction is gaining acceptance The third search was used to identify both cohorts that
among sleep apnea surgeons. included genioglossus advancement (GA) with UPPP and genio-
Uvulopalatopharyngoplasty (UPPP) is the most glossus plus hyoid suspension (GAHM) with UPPP. A PubMed
widely performed operation for OSA, although its lack of search for “genioglossus advancement” was performed in Octo-
efficacy for hypopharyngeal obstruction has been widely ber 2012, resulting in 75 potential articles. Articles were
documented. Success rates range within the literature excluded from this pool for the following reasons:
from 30% to 78%, and these studies are often con- The publication was a letter or comment.
founded with selection bias.21 At this time, there is no A genioglossus advancement procedure was not performed
consensus for which procedure is best used to address as part of the methods.
hypopharyngeal obstruction in OSA.21,22 The clinical indication was unrelated to OSA and/or snoring.
Tongue base procedures that do not remove tissue The language was not English.
aim to tether the tongue via sutures/ribbons/barbs to the The same patient results from another identified article
mandible, or to advance the tongue via mandibular oste- were being reported upon.
otomies. The purpose is to enlarge the hypopharyngeal The article was published before 1990.
airway in the anterior to posterior dimension. Proce- Lastly, only data where the surgical interventions were
dures targeting the hypopharynx have been hotly performed simultaneously (not staged) were included (e.g., if a
debated over the past few years, making this operation UPPP and GA were performed in one operation and a hyoid
an ideal one to review. suspension was subsequently performed on the failures from
The first objective of this study was to perform an the first combined operation, only the results from the
evidence-based medicine (EBM) review, based on the GA 1 UPPP were reported and the “staged” results for the
Center for Evidence Based Medicine guidelines, of the GA 1 HS 1 UPPP were discarded).
minimally invasive suture-based tongue suspension pro- To identify additional applicable literature articles, a
PubMed search for “genioglossal advancement” was performed
cedure as a stand-alone therapy for hypopharyngeal
also in October 2012, resulting in 14 potential articles. Articles
obstruction in OSA to evaluate its baseline safety and were excluded from this pool for the same reasons given above.
effectiveness. A second objective was to compare out- Lastly, the bibliography of the most recent (2006) review
comes of tongue suspension as part of a multilevel of hypopharyngeal sleep surgery,23 the most recent (2008)
approach to OSA surgery to an EBM review of genioglos- review on multilevel sleep surgery,24 and two reviews of non-
sus advancement (GA) with uvulopalatopharyngoplasty pressure sleep apnea therapies21,25 were analyzed for potential
(UPPP), and of genioglossus advancement with hyoid publications missed in the above PubMed searches for all
suspension (GAHM) with UPPP (operations considered inquiries.
the accepted standard for hypopharyngeal obstruction).
Summary and Grading of Clinical Data

MATERIALS AND METHODS
Unless otherwise noted, the definition of surgical success
We used multiple search methods, including queries of
selected is the same as used by Sher et al.,26 where a positive
PubMed, to identify the four cohorts of surgical patients as
response is defined as a 50% decrease in the respiratory dis-
described below.
turbance index (RDI) or apnea-hypopnea index (AHI) and a
The first search was to identify tongue suspension proce-
postoperative RDI or AHI < 20. For purposes of this review, RDI
dures as a stand-alone therapy for OSA. A PubMed search for
and AHI are used interchangeably in defining surgical out-
“tongue suspension” was performed in October 2012, resulting
comes and success.
in 195 potential articles. Articles were excluded from this pool
To grade the quality of each article’s research evidence, a
for the following reasons:
simplified format based on the evidence hierarchy at the Oxford
The publication was a letter or comment. Centre for Evidence-based Medicine was used.27 This grading
A tongue suspension procedure was not performed as part of system is given in Table I.
the methods. In this analysis, studies have been individually reviewed
An additional airway surgery was performed along with the and also combined to analyze the overall safety and effective-
tongue suspension. ness of the treatment. The strength of the combined conclusion
330
TABLE II. representing two different follow-up periods for their
Grades Corresponding to Levels of Evidence. patients. Both Kuhnel30 and DeRowe28 had a total of
three patients between the two studies who needed re-
Grade of
Conclusion Supporting Evidence moval of the tongue suspension suture. The causes cited
within those publications were infection and pain, which
A Consistent level 1 promptly resolved with removal of the tongue suture.
B Consistent level 2 or 3 or extrapolation The last two studies on this list, performed by Fibbi and
from level 1 Sezen, yielded better success rates than the earlier ones.
C Level 4 or extrapolation from level 2 or 3 Sezen and Fibbi chose patients with almost 50% lower
D Level 5 or troubling, inconsistent, or preoperative AHI when compared to the earlier studies.
inconclusive studies of any level of evidence Sezen also described lower suture placement with
tighter suspension, a technique that may have yielded
better results.
of this review is dependent on the quality of the available evi- The second literature review performed to identify
dence. Table II presents the grades that correspond to the levels tongue suspension in conjunction with UPPP to treat
of evidence on which the conclusions are based. OSA yielded eight publications.31,34–40 The results are
Consistent with the (2006) review of hypopharyngeal sleep presented in Table IV. A total of 167 patients were iden-
surgery,23 we then compared the results for each procedure or tified with an average BMI of 29.9. Average preoperative
each combination of procedures according to the criteria for a and postoperative AHI was 44.0 and 16.6 (62.3% reduc-
successful surgical outcome as outlined. We used the v2 test to
tion), respectively. Based on the measure of surgical suc-
determine whether there was a difference in the share of
patients with a successful outcome among treatments, and
cess defined previously, this resulted in a surgical
P < 0.05 was considered statistically significant. success rate of 62.3%. Postoperative follow-up is listed
and ranges from 3 months to 3 years. There were two
articles of level 2 evidence, and six articles of level 4 evi-
RESULTS dence. There were three patients among the cohort who
A total of 27 studies was gathered for comparison. had a reversal of their procedure. One patient had
The first literature review performed to identify tongue extrusion of the suture; another patient at 2 months fol-
suspension as a stand-alone procedure to treat OSA low-up had broken the suture; and the third patient had
yielded six publications.28–33 The results are presented persistent globus sensation, which resolved with suture
in Table III. A total of 82 patients were identified with removal.
an average body mass index (BMI) of 29.4. Average pre- The third literature review performed to identify
operative and postoperative AHI was 32.0 and 18.8 genioglossus advancement with UPPP, with or without
(41.1% reduction), respectively. Based on the measure of hyoid suspension myotomy to treat OSA, yielded 18 pub-
surgical success defined previously, this resulted in a lications.39,41–56 The results presented in Table V show
surgical success rate of 36.6%. Postoperative follow-up is the cohort of GA 1 UPPP, and the results in Table VI
listed and ranges from 2 months to 2 years. There was show the cohort of GAHM 1 UPPP.
one level 2 study, and five of level 4 studies. The data A total of 151 patients were identified in the cohort
listed from Kuhnel30 and Fibbi29 are listed twice, of GA 1 UPPP with an average BMI of 29.0. Average
TABLE III.
Suture-Based Tongue Suspension.
AHI
Surgical Patients With
Number of BMI Success Level of Diagnosis OSA Type Reversed
Patients† (average) Pre Post (%) Follow Up Author/Year Evidence Methods (I, II, III) Therapy
14 35.0 17.0 29 2 months (RDI) DeRowe et al., 2000 4 MM unknown 2

9 28.2 33.2 17.9 11 2 months (RDI) Woodson, 2000 4 MM, E unknown 0
14 28.0 35.4 24.5 21 2 months (RDI) Woodson, 2001 4 MM, E unknown 0
25 31.0 41.8 27.8 32 3 months (RDI) Kuhnel, 2005 4 CM, E unknown 1
23 31.0 44.0 30.6 30 12 months (RDI) Kuhnel, 2005* 4 CM, E unknown 1
12 28.5 14.8 4.8 67 6 months Fibbi et al., 2009 2 CM, MM, E III 0
12 28.5 14.8 8.7 42 2 years Fibbi et al., 2009* 2 CM, MM, E III 0
8 29.8 18.2 8.0 75 12 months Sezen et al., 2011 4 MRI, MM, E III 0
Total or Average 82* 29.4 32.0 18.8 36.6 3*
*Patients with data from more than one reported follow-up time point are only tallied for the index follow-up.
†
Count is only patient who received tongue suspension and had follow-up at the indicated time point.
AHI 5 apnea-hypopnea index; BMI 5 body mass index; CM 5 cephalometric analysis; E 5 endoscopy; MM 5 Mueller maneuver; MRI 5 magnetic reso-
nance imaging; OSA Type (I,II,III) 5 based on Fujita classification of hypopharyngeal obstruction (I 5 upper oropharynxy, including palate, uvula, tonsils, upper
pharynx; II 5 upper oropharynx and hypopharyngeal obstruction; III 5 hypopharyngeal obstruction, including tongue base, lingual tonsils, supraglottis, hypo-
pharynx); RDI 5 respiratory disturbance index; TS 5 tongue suspension.
331
TABLE IV.
Suture-Based Tongue Suspension Combined with Uvulopalatopharyngoplasty (UPPP).
AHI Patients
Surgical With
Patients† (average) Pre Post (%) Follow Up Author/Year Evidence Methods (I, II, III) Therapy
15 31.3 38.7 21.0 20 3–6 months Miller, et al. 2002 4 CM, MM II 2

12 31.5 42.8 67 3 months minimum Terris et al., 2002 4 CM, MM, E II 0
15 28.3 44.5 24.2 40 4–6 months Sorrenti et al., 2003 4 CM, MM, E unknown 0
9 30.9 46.0 57 4 months Thomas, et al. 2003 2 CM, MM, E II 0
22 30.3 47.5 17.3 81 6 and 12 months Omur, 2005 4 CM, MM, E II 1
54 29.6 52.8 14.1 78 3 years Vicente, 2006 4 CM, MM, E II 0
28 29.0 33.1 15.1 57 3 months Fernandez et al., 2009 2 CM, MM, E II 0
12 30.9 28.8 15.3 50 12 months Sezen et al., 2011 4 MRI, MM, E II 0
Total or Average 167 29.9 44.0 16.6 62.3 3
†
Count is only patient who received tongue suspension and had follow-up at the indicated time point.
nance imaging; OSA Type (I,II,III) 5 Based on Fujita classification of hypopharyngeal obstruction (I 5 upper oropharynxy including palate, uvula, tonsils, upper
pharynx; II 5 upper oropharynx and hypopharyngeal obstruction; III 5 hypopharyngeal obstruction, including tongue base, lingual tonsils, supraglottis, hypo-
pharynx); TS 5 tongue suspension.
preoperative and postoperative AHI was 53.2 and 23.8 genioglossus advancement, with the addition of tran-
(55.3% reduction), respectively. Based on the measure of sient dysphagia and wound dehiscence.
surgical success defined previously, this resulted in a The published studies are summarized in Table VII
surgical success rate of 61.1%. Postoperative follow-up is according to the listed procedures or combination
listed and ranges from 3 to 10 months. There was one thereof. Consistent with the most recent (2006) review of
article of level 2 evidence, and six articles of level 4 evi- hypopharyngeal sleep surgery,23 the evidence supports a
dence. Complications included tooth root injury, mild grade C recommendation. The pre- and postoperative
transient dripping of saliva and numbness of the chin, AHI and definition of surgical success as defined above
wound infections, and mandible fractures. serve as the primary mode of comparison between
A total of 467 patients were identified in the cohort patient groups. Surgical success rates for all the studies
of GAHM 1 UPPP, with an average BMI of 29.9. Average reviewed varied widely (0% to 87%). Results of a v2 test
preoperative and postoperative AHI was 54.6 and 22.7 showed that, when aggregated data are used to compare
(58.4% reduction), respectively. Based on the measure of suture-based tongue suspension with UPPP for hypo-
surgical success defined previously, this resulted in a pharyngeal obstruction in OSA against genioglossal
surgical success rate of 61.1%. Postoperative follow-up is advancement with UPPP and GAHM with UPPP,
listed and ranges from 3 months to 4 years. All articles there is no difference in reported outcome of surgical
were level 4 evidence. Complications were similar to success.
TABLE V.
Genioglossus Advancement With Uvulopalatopharyngoplasty.
AHI/RDI
Patients* (average) Pre Post (%) Follow Up Author/Year Evidence Methods (I, II, III) Therapy
23 27.5 40.7 15.4 87 6 months Emara et al., 2011 4 CM, MM, E II 0

23 30.5 46.8 17.2 70 10 months Jacobowitz 4 CM, MM, E II 0
9 32.7 58.7 14.5 78 3–6 months Johnson & Chinn, 1994 4 CM, MM, E II 0
32 n/r 50.5 20.5 69 4–6 months Lee et al, 1999 4 CM, MM, E II 0
44 28.0 62.0 29.6 52 3 months Liu et al, 2005 4 CM II 0
12 30.5 71.2 46.7 0 3 months Riley et al, 1994 4 CM, MM, E II 0
8 28.7 37.4 n/r 50 4 months Thomas et al, 2003 2 CM, MM, E II 0
Total or 151 29.0 53.2 23.8 61.1
Average
*Count is only patient who received treatment and had follow-up at the indicated time point.
AHI 5 apnea-hypopnea index; BMI 5 body mass index; CM 5 cephalometric analysis; E 5 endoscopy; OSA 5 obstructive sleep apnea; MM 5 Mueller ma-
neuver; OSA Type (I,II,III) 5 based on Fujita classification of hypopharyngeal obstruction (I 5 upper oropharynxy, including palate, uvula, tonsils, upper pharynx;
II 5 upper oropharynx and hypopharyngeal obstruction; III 5 hypopharyngeal obstruction, including tongue base, lingual tonsils, supraglottis, hypopharynx);
RDI 5 respiratory disturbance index.
332
TABLE VI.
Genioglossus Advancement, Hyoid Myotomy, and Uvulopalatopharyngoplasty.
AHI
Number of BMI Success Level of Diagnosis OSA Reversed
Patients† (average) Pre Post (%) Follow Up Author/Year Evidence Methods Type (I, II, III) Therapy
30 30.1 44.9 27.8 43 3–10 months Kezirian et al., 2010 4 CM, MM, E II 0
24 30.5 52.9 15.9 67 3–6 months Miller et al., 2004 4 CM, MM II 0
13 31.4 52.8 15.6 77 6–24 months Hsu and Brett, 2001 4 CM, MM, E II 0
46 28.9 47.9 18.6 65 3–4 years Nerunarat, 2003 4 CM, MM, E II 0
46 28.9 47.9 14.2 78 6 months Nerunarat, 2003 4 CM, MM, E II 0
31 28.8 48.2 14.5 70 8 months Nerunarat, 2003 4 CM, MM, E II 0
223 30.5 n/r n/r 60 6 months Riley et al., 1993 4 CM, MM, E II 0
31 28.5 65.9 28.6 67 6 months Sun et al., 2008 4 CM, MM, E II 0
14 31.1 46.6 23.3 57 4 months Utley et al., 1997 4 CM, MM, E II 0
11 27.8 70.5 57.4 18 6 months Vilaseca et al., 2002 4 CM, E II 0
26 65.6 30.1 46 6 months Yi et al., 2011 4 CM, E, MRI II 0
18 28.7 63.8 21.4 67 6 months Yin et al., 2007 4 CM, MM, E II 0
Total or 467* 29.9 54.6 22.7 61.1
Average
*Patients with data from more than one reported follow-up time point are only tallied for the index follow-up.
†
Count is only patient who received treatment and had follow-up at the indicated time point.
nance Imaging; OSA Type (I,II,III) 5 based on Fujita classification of hypopharyngeal obstruction (I 5 upper oropharynxy, including palate, uvula, tonils, upper
pharynx; II 5 upper oropharynx and hypopharyngeal obstruction; III 5 hypopharyngeal obstruction, including tongue base, lingual tonsils, supraglottis,
hypopharynx).
The tables for specific cohorts document a number suspension, midline glossectomy, radiofrequency abla-
of patient characteristics, including BMI, pre and post tion, mandibular osteotomy with genioglossus advance-
AHI, surgical success rate, duration of follow-up, type of ment, and maxilo-mandibular advancement. Many of
hypopharyngeal obstruction as described by Fujita,18 these procedures are associated with significant morbid-
and patients with reversed therapy. ity and change in facial anatomy and may require a per-
ioperative tracheotomy.28 We now practice in an era
where patients demand efficacious, minimally invasive
DISCUSSION procedures, followed by a reasonable recovery and
Our literature review of tongue advancement sur- return to work/life. Traditionally, obstructive sleep apnea
gery for sleep apnea is the most recent since the (2006) surgery has not followed this paradigm. Recovery from
review.23 Our article sought to narrow the focus to com- palate and hypopharyngeal surgery is painful, and time
pare tongue suspension against an “accepted standard” away from work can extend up to 3 weeks.
for hypopharyngeal surgery, genioglossus advancement The Repose Surgical Kit (CKA AirVance, Medtronic,
with UPPP, with or without hyoid suspension. A similar Inc.) was one of the first devices aimed at the tongue
comparison is made in the previous review, but results base and considered minimally invasive. The ease of use
from tongue suspension with and without UPPP are and preliminary clinical data was documented with two
grouped together and compared to GAHM with UPPP, initial articles, one by Woodson et al.33 and a second by
thus diluting the actual success rate of tongue suspen- DeRowe et al.28 Woodson reported on a patient popula-
sion with UPPP for multilevel sleep surgery. tion of snorers and mild to moderate sleep apneics, most
Surgical treatments of the tongue base and hypo- of whom had failed UPPP. He found symptomatic
pharyngeal collapse include lingual tonsillectomy, hyoid improvement in quality-of-life scales, but only a mild
TABLE VII.
Comparison of Tongue Suspension With Uvulopalatopharyngoplasty to Other Combined Procedures.
(%) Of Compared With
Level of Success Number/ Surgical Tongue Suspension
Procedure Evidence Grade Total Number Success Plus UPPP P Value
Tongue Suspension 1 UPPP Level 2 5 2; Level 4 5 6 C 104/167 62.3 N/A N/A

Genioglossus Advancement 1 UPPP Level 2 5 1; Level 4 5 6 C 92/151 61.6 No difference 0.80
Genioglossus Advancement Level 4 5 12 C 285/467 61.1 No difference 0.78
with Hyoid Suspension 1 UPPP
UPPP 5 uvulopalatopharyngoplasty.
333
effect on AHI/RDI. His support for tongue suspension obtained in patients with a BMI < 35 kg/m2.40 This article
was in conjunction with other OSA procedures in a mul- suggests long-term efficacy of tongue suspension in con-
tilevel approach. The most common complication was junction with UPPP. Suture migration may occur to some
delayed infection of the suture, thought to be due to degree as the suture or ribbon obtains equilibrium with
inadequate coverage of oral flora in the perioperative the tongue musculature, but what is difficult to ascertain
and postoperative periods. In patients where discomfort is if this migration is solely responsible for a worsening
or infection persisted, removal of the suture was easy AHI years after the surgical intervention. Other con-
and the reversibility cited as an advantage of this tech- founding variables likely play a role, such as weight gain
nique. DeRowe had better success with the Repose sys- and sleep habits. The Encore System has a radio-opaque
tem. This trial enrolled 16 patients, excluding those marker so that an assessment of suture migration can be
with a BMI over 35 and an RDI above 70 or below 12.5. accurately assessed over years of follow-up with a lateral
They noted a significant drop in RDI postoperatively, as cephalogram.
well as documented snoring improvement by bed part- As newer studies regarding CPAP compliance
ners. The complications included a floor of mouth cyst emerge, physicians will face a surge in patients seeking
that resolved with marsupialization. The other com- definitive surgical treatment. A recent study reporting
plaints were related to postoperative pain that subsided outcomes of long-term CPAP compliance and AHI reduc-
within 1 to 2 weeks. This article also supported tongue tion discovered a few important points. First, that even in
suspension/stabilization as a minimally invasive adjunct an ideal and carefully selected group of CPAP patients,
to other sleep apnea operations to appropriately satisfy CPAP cannot completely eliminate respiratory events due
the multilevel approach. to limited adherence. Second, when the reduction of the
Since these initial studies, treating the tongue base AHI is used as the criteria for treatment success, adher-
has garnered momentum among practitioners. New tech- ence needs to be taken into account when comparing
niques and devices are currently being developed that CPAP with alternative methods, especially those with
aim to improve the efficacy and reduce the morbidity of 100% compliance such as surgery. Lastly, defining treat-
hypopharyngeal interventions. Hypoglossal nerve stimu- ment success as an AHI <5 is inappropriate; even CPAP,
lation implants have been developed, and three competing which is considered the gold standard of treatment, is
companies (Inspire Medical, Inc., Apnex Medical, Inc., unable to achieve these results under everyday conditions
Imthera, Inc.) are currently working on clinical trials. when adherence is taken into account.16 In contrast, stud-
These devices target lingual advancement by stimulating ies are lacking with regard to long-term outcomes of mor-
the hypoglossal nerve during sleep. Early results for these bidity and mortality, as defined by a successful sleep
devices have been published and appear promising.57 operation yielding a >50% drop in AHI with an AHI < 20.
The Repose system requires a transoral suture As surgeons, we need to hold ourselves to a higher stand-
placed through the mucosa at the tongue base. An ard of defining success, both short term and long term,
anchor screw is placed on the inner cortex of the mandi- and evaluating the benefit of any reduction in AHI
ble, originally performed through a floor of mouth inci- through further studies. The paradigm of successful sleep
sion, although most surgeons now use a submental apnea treatment is evolving; and as more patients seek
incision for access. An adjustable tongue suspension de- surgical intervention it is important to provide minimally
vice was developed by Aspire Medical Inc., which invasive multilevel options, including tongue suspension.
included a tongue anchor and a tetherline to suspend There are some limitations of our current review.
the tongue. This device was reviewed in three trials con- Patient demographic data for each individual study was
ducted by Hamas et al.,58 Woodson et al.,59 and Pave- not available for review; as such, a t test comparison
lec.60 This device is not currently available for use due that draws from the average data among all patients,
to breakage of the anchor over time. The Encore System including the standard deviation, could not be used to
(Siesta Medical) is a newer adjustable and multilevel measure statistical significance within each study and
tongue suspension device. It includes two tongue suspen- across the aggregated study groups. Second, of the 27
sion/stabilization ribbons that utilize small screws on total studies used to create our surgical cohorts, three
the lingual cortex, which allows for chronic adjustment were of level 2 evidence; the remaining 24 were consid-
of ribbon tension, as well as a suture passer that allows ered level 4. Unfortunately, this pattern is a reflection of
for easy placement of the suspension ribbon within the studies performed within surgery and surgical subspe-
genioglossus muscle without passing through the mu- cialties, recognizing the inherent difficulty of randomiz-
cosa. The incision is hidden well beneath the submental ing patients to different surgical interventions or sham
crease. surgery to create a control group. Dominated within the
Suture migration has been discussed as a potential searchable publications are articles citing mainly level 3
reason for lack of tongue suspension efficacy over time, and 4 evidence in contrast to preferred randomized con-
although this has not been proven.32,33,35 Vincente et al. trol trials. Last, in compiling the various studies for our
has had the longest follow-up period to date at 3 years. A review based on our strict search criteria, we found
total of 54 patients were followed during this time period, some of the studies used pre- and postoperative respira-
with a 78% surgical success rate as defined by a greater tory distress index (RDI), while others used the apnea-
than 50% reduction in AHI and an AHI < 20. They per- hypopnea index (AHI). This has potential to impact the
formed tongue suspension as part of a multilevel surgery weighted averages, although consistency within each
with UPPP. It was noted that the best response was study serves as its own control.
334
It is worth mentioning that the average results 9. Young T, Finn L, Peppard PE, et al. Sleep disordered breathing and mor-
tality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008;
from GA 1 UPPP compared to GAHM 1 UPPP are simi- 31:1071–1078.
lar. One would assume that the addition of hyoid sus- 10. Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive
sleep apnoea by continuous positive airway pressure applied through
pension to the procedure would yield better results. the nares. Lancet 1981;1:862–865.
There was approximately three times the number of 11. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the
Joint National Committee on Prevention, Detection, Evaluation, and
patients in the GAHM 1 UPPP cohort. The average BMI Treatment of High Blood Pressure. Hypertension 2003;42:1206–1252.
and preoperative AHI was 1 point higher in this group 12. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular
outcomes in men with obstructive sleep apnoea-hypopnoea with or with-
as well. The choice for the additional hyoid suspension out treatment with continuous positive airway pressure: an observatio-
was likely a judgment call of the sleep surgeon, but fur- nal study. Lancet 2005;365:1046–1053.
ther controlled studies with randomization may be able 13. Weaver EM, Maynard C, Yueh B. Survival of veterans with sleep apnea:
continuous positive airway pressure versus surgery. Otolaryngol Head
to discern if hyoid suspension does indeed make a Neck Surg 2004;130:659–665.
difference. 14. Wolkove N, Baltzan M, Kamel H, Dabrusin R, Palayew M. Long-term com-
pliance with continuous positive airway pressure in patients with ob-
Developing a specific patient plan for treating sleep structive sleep apnea. Can Respir J 2008;15:365–369.
apnea is paramount in predicting success of the proce- 15. Yetkin O, Kunter E, Gunen H. CPAP compliance in patients with obstruc-
tive sleep apnea syndrome. Sleep Breath 2008;12:365–367.
dures chosen.22 In addition to physical exam, diagnostic 16. Stuck BA, Leitzbach S, Maurer JT. Effects of continuous positive airway
tests such as fiberoptic nasopharyngoscopy, and more pressure on apnea-hypopnea index in obstructive sleep apnea based on
long-term compliance. Sleep Breath 2012;16:467–471.
recently drug-induced sleep endoscopy (DISE), has 17. Friedman M, Ibrahim H, Bass L. Clinical staging for sleep-disordered
empowered physicians to objectively document the level breathing. Otolaryngol Head Neck Surg 2002;127:13–21.
18. Fujita S. Obstructive sleep apnea syndrome: pathophysiology, upper air-
of obstruction.19,20 Our literature review fulfilled both way evaluation and surgical treatment. Ear Nose Throat J 1993;72:
stated objectives. First, as a stand-alone procedure for 67–72, 5–6.
19. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy:
tongue base obstruction, tongue suspension showed a the VOTE classification. Eur Arch Otorhinolaryngol 2011;268:
success rate in approximately one-third of patients. Sec- 1233–1236.
ond, tongue suspension as part of a multilevel approach 20. Kotecha BT, Hannan SA, Khalil HM, Georgalas C, Bailey P. Sleep nasen-
doscopy: a 10-year retrospective audit study. Eur Arch Otorhinolaryngol
to sleep apnea surgery has similar success to the 2007;264:1361–1367.
“accepted standard” procedure of GAHM plus UPPP. 21. Randerath WJ, Verbraecken J, Andreas S, et al. Non-CPAP therapies in
obstructive sleep apnoea. Eur Respir J 2011;37:1000–1028.
Thus, tongue suspension is a viable alternative to treat- 22. Kezirian EJ, Hussey HM, Brietzke SE, et al. Hypopharyngeal surgery in
ing the tongue base with a lesser degree of morbidity, obstructive sleep apnea: practice patterns, perceptions, and attitudes.
Otolaryngol Head Neck Surg 2012;147:964–971.
and with the advantage of reversibility if not successful. 23. Kezirian EJ, Goldberg AN. Hypopharyngeal surgery in obstructive sleep
apnea: an evidence-based medicine review. Arch Otolaryngol Head Neck
Surg 2006;132:206–213.
CONCLUSION 24. Lin HC, Friedman M, Chang HW, Gurpinar B. The efficacy of multilevel
surgery of the upper airway in adults with obstructive sleep apnea/
Tongue suspension is effective and safe as part of a hypopnea syndrome. Laryngoscope 2008;118:902–908.
multilevel surgical approach for patients with OSA. 25. Woodson BT. Non-pressure therapies for obstructive sleep apnea: surgery
and oral appliances. Respir Care 2010;55:1314–21; discussion 21.
When paired with UPPP, tongue base suspension has an 26. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifica-
average surgical success rate of 62.3%, with results as tions of the upper airway in adults with obstructive sleep apnea syn-
drome. Sleep 1996;19:156–177.
high as 81% in appropriately selected patients. As a 27. Haynes RB, Richardson WS, Rosenberg W, Sackett DL, Straus SE. Evi-
stand-alone procedure, its success rate is 36.6%, compa- dence Based Medicine How to Practice and Teach EBM. 2nd ed. Edin-
burgh, Scotland: Churchill Livingstone; 2000.
rable to UPPP procedures for OSA success rates across 28. DeRowe A, Gunther E, Fibbi A, et al. Tongue-base suspension with a soft
the board. Tongue suspension is minimally invasive and tissue-to-bone anchor for obstructive sleep apnea: preliminary clinical
results of a new minimally invasive technique. Otolaryngol Head Neck
reversible, and in multilevel surgery as efficacious as Surg 2000;122:100–103.
the more morbid and invasive genioglossus advancement 29. Fibbi A, Ameli F, Brocchetti F, Mignosi S, Cabano ME, Semino L. Tongue
base suspension and radiofrequency volume reduction: a comparison
with or without hyoid suspension. Tongue suspension between 2 techniques for the treatment of sleep-disordered breathing.
should be considered in patients with OSA who demon- American journal of otolaryngology 2009;30:401–406.
strate tongue base obstruction. 30. Kuhnel TS, Schurr C, Wagner B, Geisler P. Morphological changes of the
posterior airway space after tongue base suspension. Laryngoscope
2005;115:475–480.
31. Sezen OS, Aydin E, Eraslan G, Haytoglu S, Coskuner T, Unver S. Modified
BIBLIOGRAPHY tongue base suspension for multilevel or single level obstructions in
sleep apnea: clinical and radiologic results. Auris Nasus Larynx 2011;38:
1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence 487–494.
of sleep-disordered breathing among middle-aged adults. N Engl J Med 32. Woodson BT. A tongue suspension suture for obstructive sleep apnea and
1993;328:1230–1235. snorers. Otolaryngol Head Neck Surg 2001;124:297–303.
2. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am 33. Woodson BT, Derowe A, Hawke M, et al. Pharyngeal suspension suture
Thorac Soc 2008;5:136–143. with repose bone screw for obstructive sleep apnea. Otolaryngol Head
3. Kapur VK, Weaver EM. Filling in the pieces of the sleep apnea-hyperten- Neck Surg 2000;122:395–401.
sion puzzle. JAMA 2012;307:2197–2198. 34. Fernandez-Julian E, Munoz N, Achiques MT, Garcia-Perez MA, Orts M,
4. Park JG, Ramar K, Olson EJ. Updates on definition, consequences, and Marco J. Randomized study comparing two tongue base surgeries for
management of obstructive sleep apnea. Mayo Clin Proc 2011;86: moderate to severe obstructive sleep apnea syndrome. Otolaryngol Head
549–554; quiz 54–55. Neck Surg 2009;140:917–923.
5. Rice TB, Strollo PJ, Jr., Morrell MJ. Update in sleep medicine 2011. Am J 35. Miller FR, Watson D, Malis D. Role of the tongue base suspension suture
Respir Crit Care Med 2012;185:1271–1274. with The Repose System bone screw in the multilevel surgical manage-
ment of obstructive sleep apnea. Otolaryngol Head Neck Surg 2002;126:
6. Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR. Circulat- 392–398.
ing cardiovascular risk factors in obstructive sleep apnoea: data from 36. Omur M, Ozturan D, Elez F, Unver C, Derman S. Tongue base suspension
randomised controlled trials. Thorax 2004;59:777–782. combined with UPPP in severe OSA patients. Otolaryngol Head Neck
7. Robinson GV, Stradling JR, Davies RJ. Sleep . 6: obstructive sleep apnoea/ Surg 2005;133:218–223.
hypopnoea syndrome and hypertension. Thorax 2004;59:1089–1094. 37. Sorrenti G, Piccin O, Latini G, Scaramuzzino G, Mondini S,
8. Stradling JR, Davies RJ. Sleep. 1: Obstructive sleep apnoea/hypopnoea Rinaldi Ceroni A. Tongue base suspension technique in obstructive
syndrome: definitions, epidemiology, and natural history. Thorax 2004; sleep apnea: personal experience. Acta Otorhinolaryngol Ital 2003;23:
59:73–78. 274–280.
335
38. Terris DJ, Kunda LD, Gonella MC. Minimally invasive tongue base sur- syndrome, or obstructive sleep apnea syndrome. Laryngoscope 1997;107:
gery for obstructive sleep apnoea. J Laryngol Otol 2002;116:716–721. 726–734.
39. Thomas AJ, Chavoya M, Terris DJ. Preliminary findings from a prospec- 51. Vilaseca I, Morello A, Montserrat JM, Santamaria J, Iranzo A. Usefulness
tive, randomized trial of two tongue-base surgeries for sleep-disordered of uvulopalatopharyngoplasty with genioglossus and hyoid advancement
breathing. Otolaryngol Head Neck Surg 2003;129:539–546. in the treatment of obstructive sleep apnea. Arch Otolaryngol Head
40. Vicente E, Marin JM, Carrizo S, Naya MJ. Tongue-base suspension in conjunc- Neck Surg 2002;128:435–440.
tion with uvulopalatopharyngoplasty for treatment of severe obstructive 52. Yi HL, Sun XQ, Chen B, et al. Z-palatopharyngoplasty plus genioglossus
sleep apnea: long-term follow-up results. Laryngoscope 2006;116:1223–1227. advancement and hyoid suspension for obstructive sleep apnea hypo-
41. Emara TA, Omara TA, Shouman WM. Modified genioglossus advancement pnea syndrome. Otolaryngol Head Neck Surg 2011;144:469–473.
and uvulopalatopharyngoplasty in patients with obstructive sleep apnea. 53. Yin SK, Yi HL, Lu WY, Guan J, Wu HM, Cao ZY. Genioglossus advance-
Otolaryngol Head Neck Surg 2011;145:865–871. ment and hyoid suspension plus uvulopalatopharyngoplasty for severe
42. Jacobowitz O. Palatal and tongue base surgery for surgical treatment of OSAHS. Otolaryngol Head Neck Surg 2007;136:626–631.
obstructive sleep apnea: a prospective study. Otolaryngol Head Neck 54. Liu SA, Li HY, Tsai WC, Chang KM. Associated factors to predict out-
Surg 2006;135:258–264. comes of uvulopharyngopalatoplasty plus genioglossal advancement for
43. Johnson NT, Chinn J. Uvulopalatopharyngoplasty and inferior sagittal obstructive sleep apnea. Laryngoscope 2005;115:2046–2050.
mandibular osteotomy with genioglossus advancement for treatment of 55. Hsu PP, Brett RH. Multiple level pharyngeal surgery for obstructive sleep
obstructive sleep apnea. Chest 1994;105:278–283. apnoea. Singapore Med J 2001;42:160–164.
44. Kezirian EJ, Malhotra A, Goldberg AN, White DP. Changes in obstructive 56. Miller FR, Watson D, Boseley M. The role of the Genial Bone Advance-
sleep apnea severity, biomarkers, and quality of life after multilevel sur- ment Trephine system in conjunction with uvulopalatopharyngoplasty
gery. Laryngoscope 2010;120:1481–1488. in the multilevel management of obstructive sleep apnea. Otolaryngol
45. Lee NR, Givens CD, Jr., Wilson J, Robins RB. Staged surgical treatment Head Neck Surg 2004;130:73–79.
of obstructive sleep apnea syndrome: a review of 35 patients. J Oral 57. Eastwood PR, Barnes M, Walsh JH, et al. Treating obstructive sleep apnea
Maxillofac Surg 1999;57:382–5. with hypoglossal nerve stimulation. Sleep 2011;34:1479–86.
46. Neruntarat C. Genioglossus advancement and hyoid myotomy under local 58. Hamans E, Boudewyns A, Stuck BA, et al. Adjustable tongue advance-
anesthesia. Otolaryngol Head Neck Surg 2003;129:85–91. ment for obstructive sleep apnea: a pilot study. Ann Otol Rhinol Laryn-
47. Neruntarat C. Genioglossus advancement and hyoid myotomy: short-term gol 2008;117:815–823.
and long-term results. J Laryngol Otol 2003;117:482–486. 59. Woodson BT, Steward DL, Mickelson S, Huntley T, Goldberg A.
48. Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea and the Multicenter study of a novel adjustable tongue-advancement device
hyoid: a revised surgical procedure. Otolaryngol Head Neck Surg 1994; for obstructive sleep apnea. Otolaryngol Head Neck Surg 2010;143:
111:717–721. 585–590.
49. Sun X, Yi H, Cao Z, Yin S. Reorganization of sleep architecture after sur- 60. Pavelec V, Hamans E, Stuck BA. A study of the new generation of the
gery for OSAHS. Acta Otolaryngol 2008;128:1242–1247. advance system tongue implants: three- and six-month effects of tongue
50. Utley DS, Shin EJ, Clerk AA, Terris DJ. A cost-effective and rational sur- to mandible tethering for obstructive sleep apnea. Laryngoscope 2011;
gical approach to patients with snoring, upper airway resistance 121:2487–2493.
336
HHS Public Access
Author manuscript
Laryngoscope. Author manuscript; available in PMC 2021 August 13.
Author Manuscript
Published in final edited form as:

Laryngoscope. 2021 July ; 131(7): 1676–1682. doi:10.1002/lary.29396.
Drug-Induced Sleep Endoscopy and Hypoglossal Nerve

Stimulation Outcomes: A Multicenter Cohort Study
Phillip Huyett, MD,
Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary,
Harvard Medical School, Boston, MA, USA
David T Kent, MD,

Author Manuscript
Department of Otolaryngology–Head and Neck Surgery, Vanderbilt University Medical Center,

Nashville, Tennessee, USA
Mark A D’Agostino, MD,

Southern New England Ear, Nose and Throat Group, New Haven, Connecticut, USA; Middlesex
Hospital, Middlesex, Connecticut, USA; Department of Surgery, Yale University School of
Medicine, New Haven, Connecticut, USA
Katherine K Green, MD, MS,

Department of Otolaryngology-Head and Neck Surgery at the University of Colorado School of
Medicine, Aurora, Colorado, USA
Ryan J Soose, MD,

UPMC Department of Otolaryngology Head and Neck Surgery, University of Pittsburgh School of
Author Manuscript
Medicine, Pittsburgh, Pennsylvania, USA
Thomas M Kaffenberger, MD,

UPMC Department of Otolaryngology Head and Neck Surgery, University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania, USA
B Tucker Woodson, MD,

Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin,
Milwaukee, Wisconsin, USA
Colin Huntley, MD,

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University,
Philadelphia, PA, USA
Author Manuscript
Maurits S Boon, MD,

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University,
Philadelphia, PA, USA
Clemens Heiser, MD,
Corresponding author: Phillip Huyett, MD, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street,
Boston, MA 02114, [email protected].
Presented at the American Academy of Otolaryngology-Head and Neck Surgery Foundation Annual Meeting in New Orleans, LA
September, 2019.
Huyett et al. Page 2
Department of Otorhinolaryngology, Head and Neck Surgery, Technische Universität München,

Author Manuscript
Munich, Germany
Amelie Birk, MD,

Department of Otorhinolaryngology, Head and Neck Surgery, Technische Universität München,
Munich, Germany
Maria V Suurna, MD,

Department of Otolaryngology-Head and Neck Surgery, Weill Cornell Medicine/New York
Presbyterian Hospital, New York, New York, USA
Ho-Sheng Lin, MD,

Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of
Medicine, Detroit, Michigan, USA
Jonathan A Waxman, MD PhD,

Author Manuscript
Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of

Medicine, Detroit, MI, USA
Eric J Kezirian, MD MPH

USC Caruso Department of Otolaryngology–Head & Neck Surgery, Keck School of Medicine of
the University of Southern California, Los Angeles, California, USA
Abstract
Objectives: To determine the association between findings of blinded reviews of preoperative
drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation for
obstructive sleep apnea (OSA).
Author Manuscript
Study Design: Retrospective, multicenter cohort study
Setting: Academic medical centers
Subjects and Methods: 343 adults were included from 10 centers. Preoperative DISE videos
were scored by 4 blinded reviewers using the VOTE Classification and evaluation of a possible
primary structure contributing to airway obstruction. Consensus DISE findings were examined
for an association with surgical outcomes based on therapy titration polysomnogram (tPSG).
Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15
events/hour.
Results: Study participants (76% male, 60.4±11.0 years old) had a BMI of 29.2±3.6 kg/m2. AHI
decreased (35.6±15.2 to 11.0±14.1 events/hour; p<0.001) on the tPSG, with a 72.6% response
rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI
Author Manuscript
improvement (−26.8 ± 14.9 vs −19.2 ± 12.8, p=0.02). Complete (vs. partial/none) tongue-related
obstruction was associated with increased odds of treatment response (78% vs. 68%, p=0.043).
Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with
lower odds of surgical response (58% vs. 74%, p=0.042).
Conclusions: DISE findings of primary tongue or velum contributions to airway obstruction

were associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral

walls. This study suggests that the role for DISE in counseling candidates for hypoglossal nerve
Author Manuscript
stimulation extends beyond solely for excluding complete concentric collapse related to the velum.
Keywords
hypoglossal nerve stimulation; upper airway stimulation; drug-induced sleep endoscopy;
obstructive sleep apnea
INTRODUCTION
Hypoglossal nerve stimulation (HNS) is FDA-approved for treatment of positive airway
pressure therapy (PAP)-intolerant moderate-severe obstructive sleep apnea (OSA) patients.
Contraindications to HNS include a number of clinical, polysomnographic and drug-induced
sleep endoscopy (DISE) criteria, largely carried over from the Stimulation Therapy for
Apnea Reduction (STAR) trial.1 Drug-induced sleep endoscopy (DISE) was incorporated
Author Manuscript
as a mandatory component of the pre-operative evaluation after Vanderveken et al.

demonstrated that complete concentric collapse at the velopharynx portended to worse
outcomes in a small number of patients.2
As with all surgical interventions for OSA, improving patient selection is of critical
importance to improving outcomes. Certain variables such as older age, female gender,
therapeutic PAP pressure less than 8cmH2O and lower oxygen desaturation index
have demonstrated associations with better response rates to HNS.3–5 In small studies,
preoperative DISE findings have not demonstrated consistent associations with HNS
outcomes.6–9
The aim of this study was to determine the association between findings of blinded reviews
Author Manuscript
of preoperative DISE and outcomes of HNS in a large multicenter cohort.
METHODS
This was a retrospective cohort study of adults undergoing HNS for OSA. Inclusion
criteria were age >21, diagnosed OSA on a preoperative sleep study, absence of prior
pharyngeal surgery beyond palatine tonsillectomy, video recorded preoperative DISE,
successful implantation of the Upper Airway Stimulation™ (Inspire Medical Systems, Inc.,
Maple Grove, MN, USA) system, and post-operative titration polysomnography (tPSG) with
or without home sleep apnea test (HSAT) performed after the tPSG.
Methods were similar to a previous study of DISE and upper airway surgery (excluding
HNS).10 Study participant data included age at system implantation, gender, body mass
Author Manuscript
index (BMI) at time of implantation, postoperative sleep studies, and tonsil size according
to Brodsky11 or Friedman classifications.12 De-identified DISE videos and study participant
data were submitted to a HIPAA-compliant, cloud-based database (Box.com) maintained
through the Keck School of Medicine of USC. DISE videos were reviewed and scored by
four physicians blinded to outcomes (P.H., D.T.K., M.A.D’A., and E.J.K.) according to the
VOTE classification.13 The VOTE classification involves scoring the overall degree (absent,
0; partial, 1; or complete, 2) and configuration (anteroposterior, lateral, or concentric) of

airway structures (Velum, Oropharyngeal lateral walls, Tongue, and Epiglottis) collapsing
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during DISE. In addition, an assessment was made of the primary structure (of the four
VOTE structures) contributing to airway obstruction. If at least two reviewers felt they were
unable to review the DISE video due to poor technical quality, the study participant was
excluded.
A priori criteria for reconciling DISE scoring disagreements to obtain consensus scores were
established. For each VOTE structure degree and configuration, agreement of at least 3/4
reviews was considered the consensus score. In cases without such agreement, the mean
score was used for degree (rounding down to the nearest integer) and no configuration was
assigned. Similarly, primary structure was assigned only if there was agreement among at
least 3/4 reviews; otherwise there was no consensus primary structure.
The tPSG was a type 1 sleep study wherein the sleep technologist remotely adjusts
Author Manuscript
stimulation parameters in an attempt to objectively identify optimal settings. The HSAT was
a type 3 sleep study without device titration. All sleep studies were scored per institution
standards, and there was no re-review of sleep study raw data for this study. Surgical
response was defined as a ≥50% decrease in the AHI to a level <15 events/hour on the tPSG
or on the HSAT, when available. A ≥50% decrease in the AHI to a level <15 events/hour on
the tPSG was used for analyses of surgical response unless specifically stated otherwise.
Data analysis was performed using Stata/IC 10.1 (StataCorp, College Station, TX, USA) and
SAS 9.4 (SAS Institute, Cary, NC, USA). Categorical variables were reported as frequency
and percentage; continuous variables were reported as mean and standard deviation.
Associations between individual DISE findings and surgical outcomes were tested. DISE
findings that were examined included: degree of obstruction (none vs. partial vs. complete),
Author Manuscript
complete vs. partial/none, complete vs. none (excluding partial), and any (complete/partial)
vs. none. The specific finding of complete concentric collapse related to the velum vs.
absence was also considered. Comparisons made for continuous variables were made using
the independent 2-sample or paired t-tests and for categorical variables using the 2-sided
Pearson χ2 test.
Logistic regression evaluated the independent association between DISE findings and
surgical response, with and without adjustment for potential confounders age, gender
and BMI. For each VOTE structure, the DISE finding most clearly associated with
outcomes in the univariate analyses was used, with a default of including each structure
as a dichotomous variable of complete vs. partial/none obstruction. P-values <0.05 were
considered statistically significant.
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A generalized linear mixed model based weighted kappa (κma) was used to test the interrater
reliability for each VOTE structure’s degree of obstruction. Fleiss’ Kappa was used to
assess the interrater reliability for the velum and epiglottis structure’s configuration along
with the primary site. Both kappa statistics range from 0 to 1, where values ≤0 indicate
poor, 0-0.20 indicate slight, 0.21-0.40 indicate fair, 0.41-0.60 indicate moderate, 0.61-0.80
indicate substantial, and 0.81-1.0 indicate almost perfect agreement. Institutional review
board approval was obtained from each participating center.

RESULTS
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The cohort included 343 adults from 10 centers (Table 1) who underwent treatment with
HNS. Table 2 presents baseline and post-treatment findings in the overall cohort (post
treatment findings on tPSG) and in the subgroup with postoperative HSAT. The cohort
primarily included middle-aged and older adults (inter-quartile range 53-69 years) who
were overweight or with Class I obesity (BMI inter-quartile range 27.0–31.7 kg/m2). No
subject had palatine tonsils with marked enlargement (3+ or 4+ on Brodsky or Friedman
classification).
Postoperative sleep studies were performed at 4.1±4.1 months (tPSG) and 16.5±10.8
(HSAT) following implantation. AHI improved in the overall cohort (tPSG) and the
subgroup with HSAT (Table 2). Response rates were higher when the postoperative AHI
was determined from the tPSG than the HSAT. Using the Sher criteria14 (≥50% decrease in
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the AHI and to <20 events/hour), the response rates were 78% and 63%, according to the
tPSG and HSAT, respectively.
Consensus ratings of DISE findings are presented in Table 3. Compared to the entire
cohort, the subgroup with HSAT had a higher proportion of subjects with concentric (vs.
anteroposterior) velum-related obstruction (19%,vs. 6%, p = 0.002), a greater degree of
oropharyngeal lateral wall-related obstruction (p = 0.028), and a lesser degree of tongue
related obstruction (p<0.001). There was fair inter-rater reliability for the degree of velum
related obstruction, otherwise there was moderate to substantial inter-rater reliability (Table
4).
Univariate analyses for the association between individual DISE findings and change in
tPSG AHI and tPSG surgical response rates are presented in Tables 5 and 6, respectively.
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In isolation, most DISE findings were not associated with HNS outcomes. For the velum,
complete obstruction was associated with a greater decrease in AHI but not a greater odds
of surgical response. In contrast, complete oropharyngeal lateral wall-related obstruction and
complete tongue-related obstruction were both associated with a greater odds of surgical
response but no difference in AHI changes.
Post-hoc analysis revealed that the associations were limited to those with preoperative
BMI greater than the median in this cohort (29.5 kg/m2). Among this subgroup, there
were associations between complete (vs. partial/none) oropharyngeal lateral wall-related
obstruction and a lower odds of surgical response (53% vs. 74%, p=0.049) and between
complete (vs. partial/none) tongue-related obstruction and a greater odds of surgical
response (81%, 56/69 vs. 65%, 66/101; p=0.025). There were no statistically significant
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associations between these DISE findings and outcomes in those in the subgroup with lower
preoperative BMI (76%, 59/78 vs. 72%, 68/95; p=0.55).
Elevated BMI was found to be associated with concentric collapse (partial and complete) but
no other DISE findings; 69% (22/32) of those with partial or complete concentric collapse
related to the velum were in the high BMI subgroup, compared to 47% (124/265) of those
with an anteroposterior configuration for velum-related obstruction and 38% (9/24) with no

velum-related obstruction (p=0.035). There was no association between epiglottis-related

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obstruction and outcomes.
Similar patterns were seen with definition of surgical response based on the HSAT (data
largely not shown), although most results were not statistically significant. Of note,
complete oropharyngeal lateral wall-related obstruction (vs. partial/none) was associated
with a decrease in surgical response according the definition requiring AHI <15 events/hour
(11% vs. 61%, p = 0.003). Complete tongue-related obstruction (vs. partial/none) was not
associated with HSAT outcomes based on this definition of surgical response (61% vs. 56%;
p=0.64).
Among the 14 study participants with complete concentric collapse related to the velum, the
surgical response rate was 57% (8/14) and 36% (5/14) for the definitions using tPSG and
threshold values of AHI <15 events/hour and <5 events/hour, respectively; both values were
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not statistically different from study participants without this DISE finding.
Consensus scores for primary structure associated with obstruction are presented for the
entire cohort and the HSAT subgroup in Table 7, along with surgical response (≥50%
decrease in the AHI to a level <15 events/hour). Overall, there were differences in odds
of surgical response according to primary structure. Specifically, for tPSG results, study
participants with a primary structure as the tongue had greater odds of surgical response
than with a primary structure of the oropharyngeal lateral walls (p=0.028). Those with a
primary structure of the velum (p=0.016) and tongue (0.002) both had better odds of surgical
response than those with the epiglottis. For HSAT results, both the velum (p=0.002) and
tongue (p=0.048) had greater odds of surgical response than for the oropharyngeal lateral
walls.
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Multivariate logistic regression results are reported in Table 8. There were no statistically
significant associations in adjusted or unadjusted analyses, but the point estimates were
consistent with results of analyses of DISE findings in isolation.
DISCUSSION
This is the largest study examining the association between DISE findings and outcomes
with HNS and the only study incorporating blinded DISE reviews from a large number of
centers.
Overall, the response rate HNS on the tPSG was similar to previous post-market studies,
although this study primarily utilized a more stringent definition of response (AHI <15
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events/hour and ≥50% decrease) than those employing the Sher criteria (AHI <20 events/
hour and ≥50% decrease). Compared to tPSG response, HSAT response rates were notably
lower, highlighting the importance of evaluating response over a full night without titration
of settings. The lower surgical response rate on the HSAT may reflect a selection bias if
study participants who did not have clinical success were more likely to undergo HSAT or
if it were solely related to differences in DISE findings for those who underwent HSAT
(lower odds of complete tongue-related obstruction; higher odds of concentric palate and
oropharyngeal lateral wall obstruction). The direct comparison of tPSG and HSAT outcomes

in those with HSATs suggests that this is unlikely to explain the findings entirely. This
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concern about the tPSG as defining optimal therapy has been noted clinically in other studies
and publications.15 The effectiveness HSAT may also always yield higher residual AHI
figures if the patient utilizes the pause feature or does not adhere to therapy for the full
study duration and is therefore untreated for portions of the night. Since our study began, the
manufacturer of this hypoglossal nerve stimulation technology has altered the post-implant
protocol to include at least a 3-month period of acclimation after activation but before
titration to enhance readiness for the tPSG and to decrease adjustments made during the
tPSG (to enable longer periods of assessments at target settings). It is yet to be seen whether
this translates to improved success rates on tPSG and in the long term.
Tongue-related obstruction has the clearest association with increasing the odds of response
to hypoglossal nerve stimulation, whether in the tPSG response rates for complete tongue
related obstruction (Table 6) or when the tongue was identified as the primary structure
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contributing to obstruction (Table 7). Given that this therapy specifically is designed to move
the tongue anteriorly, this finding is important but not surprising
The association between complete tongue-related obstruction and response rate was seen
largely in those with higher preoperative BMI. These post-hoc analyses of complete (vs.
partial/none) tongue-related obstruction and preoperative BMI subgroups showed that those
with complete tongue-related obstruction in the higher-BMI subgroup had the greatest odds
of response (81%). Based on the association between increasing BMI and fat deposition
in the tongue,16 these individuals may have OSA largely due to tongue enlargement and
HNS provides pharyngeal dilator muscle augmentation at the level of the tongue directly
addressing a key mechanism for their OSA. For those without complete-tongue related
obstruction in the higher BMI subgroup and lower response rate (65%), their OSA may be
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due to anatomic or non-anatomic factors that do not respond as clearly to this therapy.
Oropharyngeal lateral wall obstruction was associated with poorer outcomes, whether for
complete (vs. partial/none) obstruction (Table 6) or as the primary structure contributing
to airway obstruction (Table 7). Similar to the tongue base findings, post-hoc analyses
showed that the association was seen primarily with BMI greater than the median in this
cohort. This finding is consistent with our previous study showing that oropharyngeal
lateral-wall obstruction was associated with poorer outcomes for upper airway surgery
(excluding HNS)10 as well as a smaller study of HNS and mandibular advancement.9 HNS
has been shown to improve the transverse width of the hypopharyngeal airway (presumably
due to lateral displacement and/or stabilization of the oropharyngeal lateral walls) during
wakefulness and DISE.17 However, the effect on the oropharyngeal lateral walls is also
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indirect, reflecting the connections between the lateral pharyngeal soft tissues and the tongue
(glossopharyngeal coupling). These indirectly transmitted forces might not be as great
as direct forces, perhaps explaining why complete oropharyngeal lateral wall obstruction
had an association with poorer outcomes not seen for partial obstruction. Conversely,
the presence of these indirect forces may explain why partial oropharyngeal lateral wall
obstruction does not compromise outcomes of HNS, whereas both partial and complete
oropharyngeal lateral wall obstruction are associated with poorer outcomes after other

upper airway surgeries (that lack this indirect effect of glossopharyngeal coupling seen with
HNS).10
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Velum-related obstruction responded well to HNS with notable improvements in AHI

and in some cases showing that greater degrees of velum-related obstruction had greater
improvements in AHI (Table 5). There was no clear association between response rates
and velum-related degree or configuration (Table 6). Interestingly, the velum as the primary
structure contributing to airway obstruction was associated with high tPSG and HSAT
response rates, including the highest on HSAT (Table 7). This is consistent with reports
of favorable outcomes in isolated retropalatal collapse.7 The presence of palatoglossal
coupling remains the current explanation for this improvement in the retropalatal space
despite no direct innervation to the palatal musculature from the hypoglossal nerve.18,19
Gentle mandibular advancement (Esmarch Maneuver) and/or tongue manipulation have
been proposed to assess for palatoglossal coupling, but a recent paper with a relatively
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small sample size showed that mandibular advancement was not clearly associated with
hypoglossal nerve stimulation outcomes.9
There was no statistically-significant association between outcomes and complete concentric

collapse related to the velum, although there were relatively few (n=14) participants with
this DISE finding. DISE is currently a required preoperative evaluation for determining
candidacy for HNS to exclude individuals with complete concentric collapse related to
the velum from undergoing treatment with this modality. This has been incorporated
into indications from the US Food and Drug Administration and other governmental
bodies because of this use of DISE in the STAR Trial.1 That major role in procedure
selection was based on an early, small study of this technology showing poorer outcomes
in individuals with complete concentric collapse of the velum,2 even though there were
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potential confounders, including a change in implant technique between subgroups, moving

from placement of the stimulation lead on a proximal to distal portion of the hypoglossal
nerve (i.e., stimulating both protrusor and retrusor muscles of the tongue vs. protrusor
muscles preferentially). Complete concentric collapse related to the velum is a relatively
common DISE finding associated with OSA severity, non-positional OSA and obesity.20,21
We believe that while this study is small (although there are no published studies with larger
samples having this finding), it suggests that some patients with this DISE finding will
respond well, even if the response rates are lower (58% with vs. 73% without). It is worth
noting that this figure is similar or higher than response rates seen with other DISE findings,
specifically the oropharyngeal lateral walls and epiglottis.
Epiglottis-related obstruction was associated with the lowest response rates, especially in
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those with the epiglottis as the primary structure contributing to airway obstruction. Future
studies are needed to clarify the role of HNS in patients with isolated epiglottic collapse.
This study has important limitations. First, we used AHI reported by the sleep center as the
primary measure of outcomes because it was recorded universally, but we did not evaluate
other potential objective and subjective measures: AHI scored by review of raw sleep study
data, oxygen desaturation index,15 Epworth Sleepiness Scale, and Functional Outcomes
of Sleep Questionnaire, to name just a few. The inter-rater reliability demonstrated a

range of fair to substantial agreement on VOTE and primary site scoring, reflecting the
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known subjectivity of DISE. To overcome this, we used conservative criteria for developing
consensus scores and used only those. We also intentionally did not exclude outlier scoring
to improve the external validity of these results. Even in the largest study of its kind, the
sample sizes for specific DISE findings were small, in many cases, solely because these
patterns are less common or because individuals with these findings were generally excluded
from treatment (complete concentric collapse related to the velum).
CONCLUSIONS
DISE is required for preoperative evaluation prior to hypoglossal nerve stimulation in
order to exclude those with complete concentric collapse related to the velum. Certain
other findings are associated with surgical outcomes, suggesting a wider role for DISE in
treatment selection.
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Acknowledgement:
The authors would like to thank biostatistician Melissa Mert, MS for her contribution to the research.
Funding and Conflicts of Interest:

The study was supported by a Health Services Research Grant from the American Academy of Otolaryngology
– Head and Neck Surgery Foundation and an Investigator-Initiated Research Support grant from Inspire Medial
Systems, Inc. This work was also supported by grants UL1TR001855 and UL1TR000130 from the National Center
for Advancing Translational Science (NCATS) of the U.S. National Institutes of Health. The content is solely
the responsibility of the authors and does not necessarily represent the official views of the National Institutes of
Health.
REFERENCES
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1. Strollo PJ Jr., Soose RJ, Maurer JTet al.Upper-airway stimulation for obstructive sleep apnea. N
Engl J Med2014; 370:139–149. [PubMed: 24401051]
2. Vanderveken OM, Maurer JT, Hohenhorst Wet al.Evaluation of drug-induced sleep endoscopy as
a patient selection tool for implanted upper airway stimulation for obstructive sleep apnea. J Clin
Sleep Med2013; 9:433–438. [PubMed: 23674933]
3. Woodson BT, Strohl KP, Soose RJet al.Upper Airway Stimulation for Obstructive Sleep Apnea:
5-Year Outcomes. Otolaryngol Head Neck Surg2018; 159:194–202. [PubMed: 29582703]
4. Thaler E, Schwab R, Maurer Jet al.Results of the ADHERE upper airway stimulation registry and
predictors of therapy efficacy. Laryngoscope2020; 130:1333–1338. [PubMed: 31520484]
5. Lee CH, Seay EG, Walters BK, Scalzitti NJ, Dedhia RC. Therapeutic Positive Airway Pressure
Level Predicts Response to Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea. J Clin
Sleep Med2019; 15:1165–1172. [PubMed: 31482839]
6. Ong AA, Murphey AW, Nguyen SAet al.Efficacy of Upper Airway Stimulation on Collapse Patterns
Observed during Drug-Induced Sedation Endoscopy. Otolaryngol Head Neck Surg2016; 154:970–
Author Manuscript
977. [PubMed: 26980916]

7. Mahmoud AF, Thaler ER. Outcomes of Hypoglossal Nerve Upper Airway Stimulation among
Patients with Isolated Retropalatal Collapse. Otolaryngol Head Neck Surg2019; 160:1124–1129.
[PubMed: 30857472]
8. Xiao R, Trask DK, Kominsky AH. Preoperative Predictors of Response to Hypoglossal Nerve
Stimulation for Obstructive Sleep Apnea. Otolaryngol Head Neck Surg2020; 162:400–407.
[PubMed: 31959054]
9. Mulholland GB, Dedhia RC. Success of Hypoglossal Nerve Stimulation Using Mandibular
Advancement During Sleep Endoscopy. Laryngoscope2020.

10. Green KK, Kent DT, D’Agostino MAet al.Drug-Induced Sleep Endoscopy and Surgical Outcomes:
A Multicenter Cohort Study. Laryngoscope2019; 129:761–770. [PubMed: 30588639]
Author Manuscript
11. Brodsky LModern assessment of tonsils and adenoids. Pediatr Clin North Am1989; 36:1551–1569.
[PubMed: 2685730]
12. Friedman M, Ibrahim H, Bass L. Clinical staging for sleep-disordered breathing. Otolaryngol Head
Neck Surg2002; 127:13–21. [PubMed: 12161725]
13. Kezirian EJ, Hohenhorst W, de Vries N. Drug-induced sleep endoscopy: the VOTE classification.
Eur Arch Otorhinolaryngol2011; 268:1233–1236. [PubMed: 21614467]
14. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway
in adults with obstructive sleep apnea syndrome. Sleep1996; 19:156–177. [PubMed: 8855039]
15. Dedhia RC, Woodson BT. Standardized Reporting for Hypoglossal Nerve Stimulation Outcomes. J
Clin Sleep Med2018; 14:1835–1836. [PubMed: 30373702]
16. Kim AM, Keenan BT, Jackson Net al.Tongue fat and its relationship to obstructive sleep apnea.
Sleep2014; 37:1639–1648. [PubMed: 25197815]
17. Safiruddin F, Vanderveken OM, de Vries Net al.Effect of upper-airway stimulation for obstructive
sleep apnoea on airway dimensions. Eur Respir J2015; 45:129–138. [PubMed: 25186270]
Author Manuscript
18. Heiser C, Edenharter G, Bas M, Wirth M, Hofauer B. Palatoglossus coupling in selective upper
airway stimulation. Laryngoscope2017; 127:E378–e383. [PubMed: 28105667]
19. Goding GS Jr., Tesfayesus W, Kezirian EJ. Hypoglossal nerve stimulation and airway changes
under fluoroscopy. Otolaryngol Head Neck Surg2012; 146:1017–1022. [PubMed: 22307575]
20. Kastoer C, Benoist LBL, Dieltjens Met al.Comparison of upper airway collapse patterns and its
clinical significance: drug-induced sleep endoscopy in patients without obstructive sleep apnea,
positional and non-positional obstructive sleep apnea. Sleep & breathing = Schlaf & Atmung2018;
22:939–948. [PubMed: 30069673]
21. Steffen A, Frenzel H, Wollenberg B, König IR. Patient selection for upper airway stimulation: is
concentric collapse in sleep endoscopy predictable?Sleep & breathing = Schlaf & Atmung2015;
19:1373–1376. [PubMed: 26483263]
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Table 1.
Distribution of study participants across centers

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Center No. Study Participants (n=343) Percent of Total Cohort

MCW 43 12.5
MSH 14 4.1
MUN 35 10.2
TJUH 42 12.2
UC 32 9.6
UPMC 90 26.2
USC 18 5.3
VUMC 27 7.9
WCM 28 8.2
WSU 13 3.8
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Table 2.
Patient characteristics.
Baseline (n=343) tPSG (n=343) HSAT Subgroup Baseline (n=110) HSAT (n=110)
Huyett et al.
Age at surgery, years 60.4 ± 11.0 59.3 ± 10.4
Male gender 258 (76.1%) 91 (82.7%)
BMI, kg/m2 29.2 ± 3.6 28.5 ± 3.6* 29.6 ± 3.5 28.4 ± 3.6*
AHI 35.6 ± 15.2 11.0 ± 14.1* 35.6 ± 14.3 15.9 ± 16.0*
OSA severity
None (AHI <5) 0 (0%) 146 (42.6%) 0 (0%) 30 (27.3%)
Mild (AHI 5- <15) 7 (2.0%) 112 (32.7%) 0 (0%) 41 (37.3%)
Moderate (AHI 15- <30) 134 (39.1%) 61 (17.8%) 43 (39.1%) 22 (20.0%)
Severe (>30) 202 (58.9%) 24 (7.0%) 67 (60.9%) 17 (15.5%)
Response rate 15 (≥50% decrease in the AHI to <15 events/hour) 249 (72.6%) 63 (57.3%)
Response rate 5 (≥50% decrease in the AHI to <5 events/hour) 151 (44.0%) 30 (27.3%)
SD = standard deviation, tPSG = titration in lab polysomnogram, eHSAT = efficacy home sleep apnea test, BMI = body mass index, AHI = apnea hypopnea index, OSA = obstructive sleep apnea.
*
p < 0.05, comparing preoperative to postoperative values

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Table 3.
DISE findings: VOTE Classification and primary structure for overall cohort
Structure § Degree of Obstruction (0/1/2) Primary structure

Configuration
Huyett et al.
Velum* Anteroposterior Concentric 24/169/150 67

0/138/127 0/18/14
Oropharynx lateral walls 220/90/33 39
Tongue 74/122/147 154
Epiglottis Anteroposterior Lateral 294/33/16 9

0/28/12 0/5/4
§
In some cases, there was no agreement on configuration, making the total amounts based on configuration findings differ from those for degree of obstruction.
*
There was no lateral velum-related obstruction

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Table 4.
Interrater reliability VOTE classification findings and primary site.
Structure Degree of obstruction Configuration

Huyett et al.
κma SE 95% CI Fleiss Kappa SE p-value
Velum 0.30 0.06 0.19-0.42 0.42 0.02 <0.001
Oropharynx lateral walls 0.48 0.08 0.33-0.63
Tongue 0.59 0.02 0.54-0.63
Epiglottis 0.85 0.01 0.83-0.87 0.63 * *

Primary Site - - - 0.41 0.01 <0.001
*
Unable to calculate due to substantial missing data (no configuration identified because no obstruction related to the epiglottis)
CI = confidence interval; SE = standard error.

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Table 5.
Change in AHI on titration PSG associated with DISE findings
DISE Finding Mean change in AHI ± SD p-value

Huyett et al.
V None vs partial vs complete −19.2 ± 12.8 vs −23.5 ± 18.5 vs 26.8 ± 14.9
Complete vs partial/none −27.0 ± 14.9 vs −23.0 ± 17.8 0.04
Complete vs partial* −26.8 ± 14.9 vs −23.5 ± 18.5 0.09
Any vs none −25.0 ± 16.9 vs −19.2 ± 12.8 0.10
CCC presence vs absence −23.6 ± 13.3 vs −24.7 ± 16.8 0.80
Complete vs none −26.8 ± 14.9 vs −19.2 ± 12.8 0.02
O None vs partial vs complete −23.8 ± 16.6 vs −26.9 ± 17.1 vs −24.4 ± 15.8
Any vs none −26.2 ± 16.8 vs −23.8 ± 16.6 0.19
T None vs partial vs complete −23.4 ± 18.7 vs −26.5 ± 16.7 vs −23.8 ± 15.5
Any vs none −25.0 ± 16.1 vs −23.4 ± 18.7 0.47
E None vs partial vs complete −24.6 ± 16.7 vs −25.0 ± 14.3 vs −25.0 ± 21.6
Any vs none −25.0 ± 16.8 vs −24.6 ± 16.7 0.87

Bold values indicate statistically significant findings.
*
In some cases, there was no consensus on configuration, making the total amounts based on configuration findings differ from those for degree of obstruction.
DISE = drug induced sleep endoscopy, AHI = apnea hypopnea index, V = velopharynx, CCC = complete concentric collapse, O = oropharyngeal lateral walls, T = tongue, E = epiglottis
Page 15
Table 6.
Surgical response (≥50% decrease in AHI to <15 events/hour) on tPSG and association with DISE findings
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DISE finding N (%) p-value
V None vs partial vs complete 19 (79.2%) vs 116 (68.6%) vs 114 (76.0%) 0.29
Complete vs partial/none 114 (76.0%) vs 135 (69.9%) 0.22
Complete vs partial* 114 (76.0%) vs 116 (68.6%) 0.17
Any vs none 230 (72.1%) vs 19 (79.2%) 0.64
Complete vs none 114 (78.0%) vs 19 (79.2%) 1.00
Complete concentric collapse: presence vs absence 8 (57.6%) vs 241 (73.0%) 0.22
O None vs partial vs complete 163 (74.1%) vs 67 (74.4%) vs 19 (57.6%) 0.13

Any vs none 86 (69.9%) vs 163 (74.1%) 0.41
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T None vs partial vs complete 48 (64.9%) vs 86 (70.5%) vs 115 (78.2%) 0.09

Any vs none 201 (74.7%) vs 48 (64.9%) 0.09
E None vs partial vs complete 216 (73.5%) vs 24 (72.7%) vs 9 (56.3%) 0.32
Any vs none 33 (67.3%) vs 216 (73.5%) 0.37
Bold values indicate statistically significant findings.

*
In some cases, there was no consensus on configuration, making the total amounts based on configuration findings differ from those for degree of
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obstruction.
DISE = drug induced sleep endoscopy, V = velum, CCC= complete concentric collapse, O = oropharyngeal lateral walls, T = tongue, E = epiglottis
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Table 7.
Surgical response according to DISE primary structure contributing to airway obstruction.

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tPSG (N, %)* Success tPSG HSAT (N, %)* Success HSAT
V 67 (25%) 49/67 (73.1%) 39 (45%) 29/39 (74.4%)
O 39 (14%) 24/39 (61.5%) 14 (16%) 4/14 (28.6%)
T 154 (57%) 121/154 (78.6%) 30 (34%) 18/30 (60.0%)
E 9 (3%) 3/9 (33.3%) 4 (5%) 2/4 (50.0%)
p=0.007 p=0.025
tPSG = in lab titration study, eHSAT = efficacy home sleep apnea test
*
Total N does not match cohort or subgroup total because some study participants did not have consensus primary structure contributing to
obstruction
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Table 8.
Logistic regression analyses for odds ratios reflecting association between surgical response (tPSG) and
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specific DISE findings (complete vs. partial/none structure-related obstruction).
Unadjusted (n=275) Adjusted (n=258)
Odds Ratio 95% CI Odds Ratio 95% CI

Velum 1.49 (0.67, 3.34) 1.51 (0.67, 3.40)
Oropharynx lateral walls 0.52 (0.24, 1.12) 0.57 (0.26, 1.22)
Tongue base 1.25 (0.68, 2.29) 1.12 (0.60, 2.09)
Epiglottis 0.75 (0.39, 1.47) 0.80 (0.40, 1.57)
Age (years) --- --- 1.01 (0.99, 1.01)
Male Gender --- --- 0.59 (0.31, 1.13)
BMI (kg/m2) --- --- 0.97 (0.90, 1.04)

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BMI = body mass index; CI = confidence interval.

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https://doi.org/10.5664/jcsm.9592
SPECIAL ARTICLES
Referral of adults with obstructive sleep apnea for surgical consultation: an

American Academy of Sleep Medicine clinical practice guideline
David Kent, MD1; Jeffrey Stanley, MD2; R. Nisha Aurora, MD, MHS3; Corinna Levine, MD, MPH4; Daniel J. Gottlieb, MD, MPH5; Matthew D. Spann, MD1;
Carlos A. Torre, MD4; Katherine Green, MD, MS6; Christopher G. Harrod, MS7
1
Vanderbilt University Medical Center, Nashville, Tennessee; 2University of Michigan, Ann Arbor, Michigan; 3Rutgers Robert Wood Johnson Medical School, New Brunswick, New
Jersey; 4University of Miami, Miller School of Medicine, Miami, Florida; 5VA Boston Healthcare System, Brigham and Women’s Hospital, Boston, Massachusetts; 6University of
Colorado, Aurora, Colorado; 7American Academy of Sleep Medicine, Darien, Illinois
Introduction: This guideline establishes clinical practice recommendations for referring adults with obstructive sleep apnea (OSA) for surgical consultation.
Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine, otolaryngology, and bariatric surgery to develop
recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force
evaluated the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that
support the recommendations. The AASM Board of Directors approved the final recommendations.
Recommendations: The following recommendations are intended as a guide for clinicians who treat adults with OSA. Each recommendations statement
Downloaded from jcsm.aasm.org by 64.124.192.2 on January 25, 2022. For personal use only. No other uses without permission.
is assigned a strength (“Strong” or “Conditional”). A “Strong” recommendation (ie, “We recommend … ”) is one that clinicians should follow under most
circumstances. A “Conditional” recommendation is one that requires that the clinician use clinical knowledge and experience and strongly consider the
patient’s values and preferences to determine the best course of action. (1) We recommend that clinicians discuss referral to a sleep surgeon with adults with
OSA and BMI <40 kg/m2 who are intolerant or unaccepting of PAP as part of a patient-oriented discussion of alternative treatment options (STRONG). (2) We
recommend that clinicians discuss referral to a bariatric surgeon with adults with OSA and obesity (class II/III, BMI ≥35 kg/m2) who are intolerant or
unaccepting of PAP as part of a patient-oriented discussion of alternative treatment options (STRONG). (3) We suggest that clinicians discuss referral to a
sleep surgeon with adults with OSA, BMI <40 kg/m2, and persistent inadequate PAP adherence due to pressure-related side effects as part of a patient-
oriented discussion of adjunctive or alternative treatment options (CONDITIONAL). (4) We suggest that clinicians recommend PAP as initial therapy for adults
with OSA and a major upper airway anatomic abnormality prior to consideration of referral for upper airway surgery (CONDITIONAL).
Keywords: upper airway surgery, hypoglossal nerve stimulation, bariatric surgery, maxillomandibular advancement, obstructive sleep apnea
Citation: Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine clinical
practice guideline. J Clin Sleep Med. 2021;17(12):2499–2505.
INTRODUCTION This guideline, in conjunction with the accompanying

Copyright 2022 American Academy of Sleep Medicine. All rights reserved.
systematic review,2 provides a comprehensive update of the

This clinical practice guidelineis intended toreplace the previously available evidence and is designed to provide recommenda-
published 2010 American Academy of Sleep Medicine (AASM) tions for when health care providers treating OSA should dis-
guideline on the use of surgery to treat adults with obstructive sleep cuss referral for upper airway or bariatric surgery evaluation
apnea (OSA)1 and reflects the current recommendations of the with adult patients with OSA. It intentionally does not provide
AASM. Positive airway pressure (PAP) is well recognized as the recommendations for individual surgical procedures and
most efficacious treatment for OSA, but therapy effectiveness instead focuses on the body of evidence surrounding surgery
may be compromised when patients are unable to sufficiently as a treatment option in the setting of residual or untreated
adhere to therapy or obtain adequate benefit. For some patients OSA. It informs clinical care by considering specific, com-
struggling with PAP, surgery may therefore be a less efficacious monly encountered clinical scenarios in which consideration
yet ultimately a more effective treatment option. The 2010 guide- of surgery may provide patient benefit, acknowledging that
line made recommendations for specific surgical procedures, but it the tools and knowledge base needed for comprehensive
did not address the critical question of when to consider surgical anatomic evaluation and patient counseling regarding the sur-
treatment options.1 The current guideline seeks to recognize clini- gical experience are outside the practice boundaries of most
cal scenarios where such compromises should be discussed and to health care providers. Procedural selection is a complex deci-
provide a framework for explicitly addressing the role of patient- sion requiring an informed discussion of risks and benefits
specific values and preferences in the creation of a customized surrounding anatomically appropriate options that incorporates
treatment plan evaluating the risks, benefits, costs, and side effects patient-specific values and preferences. Collaborative commu-
associated with various medical and surgical therapies. nication about patient care between a consulting surgeon and a
Journal of Clinical Sleep Medicine, Vol. 17, No. 12 2499 December 1, 2021
D Kent, J Stanley, RN Aurora, et al. Referral of adults with OSA for surgical consultation
referring health care provider, leveraging each one’s areas of guideline and the supporting systematic review. Members of
expertise, is the management pathway most likely to yield sat- the TF were required to disclose all potential conflicts of interest
isfactory outcomes. (COI), per the AASM’s COI policy, prior to being appointed to
This guideline utilizes available evidence to support recom- the TF and throughout the research and writing of these docu-
mendations regarding discussion of referral in the following ments. In accordance with the AASM’s conflicts of interest pol-
scenarios: icy, TF members with a Level 1 conflict were not allowed to
participate. TF members with a Level 2 conflict were required
(1) Patients who are intolerant or unaccepting of PAP therapy to recuse themselves from any related discussion or writing
(2) Patients who have persistent inadequate PAP adherence responsibilities. All relevant conflicts of interest are listed in
due to pressure-related side effects the Disclosures section.
(3) Patients with obvious upper airway anatomic abnor- The TF conducted a systematic review of the published scien-
malities potentially amenable to surgery as initial OSA tific literature, focusing on patient-oriented, clinically relevant
treatment outcomes to answer 4 PICO (Patient, Intervention, Comparison,
The treatment of adults with OSA should be based on a diagnosis of and Outcomes) questions regarding the surgical treatment of
OSA established using objective testing performed in adults with OSA. This review was designed to determine if surgi-
conjunction with a comprehensive sleep evaluation. For this guide- cal therapies for OSA are effective for improving outcomes of
line, the terminology “discuss referral” implies a discussion interest when analyzed collectively, which will inform recom-
between the patient and health care provider regarding the option mendations for when health care providers treating OSA (subse-
of surgical consultation as part of a comprehensive discussion of quently referred to as “sleep clinicians” in this document) should
alternative treatment options to PAP. Under ideal circumstances, discuss referral for upper airway or bariatric surgery evaluation
patients with inadequate PAP utilization will have had an opportu- with adults with OSA. Surgical procedures included pharyngeal
nity to consult with a sleep medicine professional to address bar- soft tissue modifications, skeletal modification, and upper airway
riers to adherence, although access to such resources may be stimulation, as described further in the accompanying systematic
limited in some areas.3 A threshold for adequate PAP adherence review. Meta-analyses were performed on outcomes of interest,
will vary between patients depending on their individual underly- when possible, for each PICO question. Patients unaccepting
ing medical history, symptomatology, disease severity, and of PAP were considered untreated for the purpose of these
response to PAP, and should be part of the discussion between analyses. Therefore, comparisons of surgery to no treatment
the health care provider and patient. “Sleep surgeon” refers to an and/or assessment of efficacy before and after surgery to treat
otolaryngologist or oral and maxillofacial surgeon with training OSA in adult patients were performed. The clinical practice rec-
and expertise in upper airway surgery who has an appropriate ommendations were then developed according to the Grading of
understanding of sleep medicine and modern surgical techniques Recommendations Assessment, Development and Evaluation
for the treatment of OSA. If the patient elects for referral, the (GRADE) process.4 The TF assessed the following 4 components
standard surgical consultation includes a detailed anatomic assess- to determine the direction and strength of a recommendation:
ment for surgical treatment occasionally using tools unavailable to quality of evidence, balance of beneficial and harmful effects,
the average health care provider, such as flexible fiber-optic laryn- patient values and preferences, and resource use. Details of these
goscopy. A discussion of the individual’s expected risks and bene- assessments can be found in the accompanying systematic
fits of each appropriate treatment option is part of the standard review.2 Additional information is provided in the form of
“Remarks” immediately following the recommendation state-
informed consent process with the surgeon, including the risk of

residual OSA. Following the principle of primum non nocere ments, when deemed necessary by the TF. Remarks are based
(“First, do no harm”), it is expected that surgery proceed only on the evidence evaluated during the systematic review and are
once the surgeon and patient have mutually agreed upon an accept- intended to provide context for the recommendations and to
able risk profile. Inherent to this evaluation is the understanding guide clinicians in the implementation of the recommendations
that somereferred patients willnot beappropriatefor surgical inter- in daily practice.
ventions and are expected to be counseled as such by surgical col- A draft of the guideline and systematic review was made avail-
leagues. It is additionally understood that many patients will able for public comment for a 4-week period on the AASM web-
ultimately elect against surgical therapy after an informed discus- site. The TF took into consideration all the comments received
sion with a surgeon. These individuals should be referred back to and made decisions about whether to revise the draft based on
the health care provider for further OSA management. All patients the comments. The revised guideline and systematic review
should receive follow-up care to re-evaluate OSA symptoms; were submitted to the AASM Board of Directors for subsequent
residual sleep-related symptoms, including residual sleep- approval.
disordered breathing, should be evaluated and addressed.
RECOMMENDATIONS
METHODS
The recommendations in this guideline define principles of prac-
The AASM commissioned a task force (TF) of experts in sleep tice that should meet the needs of most patients in most situations.
medicine, otolaryngology, and bariatric surgery to develop this Each recommendation statement was assigned a strength
(“Strong” or “Conditional”). A “Strong” recommendation is one studies showingclinically meaningful andbeneficial differences in
that clinicians should follow for almost all patients (ie, something nearly all critical outcomes, and the benefits of discussing referral
that might qualify as a quality measure). A “Conditional” recom- over the harms of no treatment.
mendation reflects a lower degree of certainty in the appropriate- The TF investigated the use of upper airway surgery as rescue
ness of the patient care strategy for all patients. It requires that the therapy for adults with OSA who were intolerant or unaccepting
clinician use clinical knowledge and expertise and strongly con- of positive airway pressure (PAP) to improve 1 or more of the fol-
siders the individual patient’s values and preferences to deter- lowing critical outcomes: excessive sleepiness, sleep quality,
mine the best course of action. The ultimate judgment quality of life (QOL), snoring, blood pressure (BP), apnea-
regarding any specific care must be made by the treating clinician hypopnea index (AHI), and respiratory disturbance index
and the patient, taking into consideration the individual circum- (RDI). The TF also considered the risks of perioperative death
stances of the patient, available treatment options, and resources. and permanent dysphagia as critical outcomes for decision-
The AASM expects this guideline to have an impact on profes- making. Meta-analyses demonstrated a clinically significant
sional behavior, patient outcomes, and—possibly—health care reduction in excessive sleepiness, snoring, BP, and AHI/RDI,
costs. This clinical practice guideline reflects the state of knowl- and a clinically significant improvement in sleep-related and gen-
edge at the time of publication and will be reviewed and updated eral QOL. The results of the meta-analyses also demonstrated no
as new information becomes available. clinically significant risk of permanent dysphagia. The incidence
The following clinical practice recommendations are based of perioperative death was not reported in the studies.
on a systematic review and evaluation of evidence using the The overall quality of evidence was low due to imprecision and
GRADE process. The implications of the strength of recommen- risk of bias associated with observational studies. The potential
dations for guideline users are summarized in Table 1. Remarks benefits of upper airway surgery as a rescue therapy include a
are provided to guide clinicians in the implementation of these reduction in excessive sleepiness, snoring, BP, and AHI/RDI,
recommendations. and an improvement in QOL in patients unaccepting of PAP ther-
apy. Benefits demonstrated in the literature are limited to patients
Surgical treatment of patients who are intolerant or considered appropriate for surgery by the treating surgeon and
unaccepting of PAP may not be representative of all patients with OSA. The potential
harms of upper airway surgery include short-term discomfort that
Recommendation 1: We recommend that clinicians discuss is expected during postoperative recovery and is discussed during
referral to a sleep surgeon with adults with OSA and BMI < the preoperative informed consent process between the surgeon
40 kg/m2 who are intolerant or unaccepting of PAP as part and patient. Additionally, potential persistent long-term side
of a patient-oriented discussion of alternative treatment effects have been reported including dysphagia, taste alteration,
options (STRONG). mandibular paresthesia, perceived worsening of facial appear-
Remarks: The recommendation to discuss referral is not ance, aspiration, hemorrhage, and globus pharyngeus, but the
required to result in referral and does not preclude patient con- incidence of these is low. Surgery carries inherent risks, but based
sideration of other viable alternative treatment options (eg, man- on their combined clinical expertise and the substantial effects of
dibular advancement device, positional therapy, lifestyle surgery on objective and subjective measures of disease, the TF
changes). The strong recommendation to discuss surgical refer- judged that the potential benefits of a discussion regarding refer-
ral with patients with a BMI < 40 kg/m2 is not a recommendation ral to a sleep surgeon with patients unaccepting of PAP therapy
outweigh the potential harms of untreated OSA. The TF observed
against (and does not preclude) discussion of surgical referral

with patients with a BMI ≥ 40 kg/m2 if the health care provider that the balance of risks vs benefits for upper airway surgery is
deems it an appropriate management discussion point. For highly dependent upon an individual patient’s OSA severity,
patients within the BMI range of 35–40 kg/m2, discussion regard- symptoms, medical comorbidities, and selected surgical therapy
ing a referral to both sleep and bariatric surgeons (as per Recom- but noted that a discussion of individualized risks and benefits
mendation 2) to discuss management options is appropriate. is a standard component of the preoperative informed consent
process. There are insufficient data to assess differences in
The TF made a strong recommendation in favor of discussing resource requirements for surgical referral vs no treatment.
surgical referral based on a large body of low-quality evidence Because acceptability of surgical interventions varies and there
from 4 randomized controlled trials (RCTs) and 239 observational is little harm in discussing a referral, based on their combined
Table 1—Implications of strong and conditional recommendations for users of AASM clinical practice guidelines.
Strong recommendation Almost all patients should receive the recommended course of action. Adherence to this recommendation could
“We recommend … ” be used as a quality criterion or performance indicator.
Conditional recommendation Most patients should receive the suggested course of action; however, different choices may be appropriate for
“We suggest … ” different patients. The clinician must help each patient determine if the suggested course of action is
clinically appropriate and consistent with his or her values and preferences.
The ultimate judgment regarding the suitability of any specific recommendation must be made by the clinician and patient.
clinical expertise the TF judged that most patients would gener- patients with obesity and OSA. While the benefits of bariatric sur-
ally be accepting of a discussion regarding referral. The choice gery are clinically significant, the surgeon needs to consider fac-
to pursue referral is expected to vary between patients based on tors that would make a patient at higher risk for surgical
personal values, beliefs, and expectations for recovery time or intervention, which are not captured by this analysis. Selection
pain with surgery. bias may be present in the observed outcomes as adherence
with lifestyle changes is required of patients undergoing bariatric
Surgical treatment of patients with obesity with surgery. It is difficult to determine whether the effects of bariatric
bariatric surgery surgery on BP and the Epworth Sleepiness Scale (ESS) are
directly attributed to weight loss from surgery or the lowering
Recommendation 2: We recommend that clinicians discuss
of AHI. Potential harms of bariatric surgery include short-term
referral to a bariatric surgeon with adults with OSA and obe-
discomfort that is expected during postoperative recovery and
sity (class II/III, BMI ≥ 35) who are intolerant or unaccepting
is discussed during the preoperative informed consent process
of PAP as part of a patient-oriented discussion of alternative
between the surgeon and patient. Additionally, iron malabsorp-
treatment options (STRONG).
tion, gastric ulcer, vitamin deficiency, bowel obstruction or
Remarks: The recommendation to discuss referral is not leak, gastrointestinal reflux disorder, and gastric band slippage
required to result in referral and does not preclude patient con- have been reported but the incidence of these is low. Bariatric sur-
sideration of medical weight loss strategies or other viable alter- gery carries inherent risks but based on their combined clinical
native treatment options for OSA. For patients within the BMI expertise and the substantial effects of bariatric surgery on objec-
range of 35–40 kg/m2, discussion regarding a referral to both tive and subjective measures of disease, the TF judged that the
sleep and bariatric surgeons (as per Recommendations 1 and potential benefits of a discussion regarding referral to a bariatric
3) to discuss management options is appropriate. The strong rec- surgeon with patients who are intolerant or unaccepting of PAP
ommendation to discuss surgical referral with patients with OSA, therapy outweigh the potential harms of untreated OSA. The
obesity, and PAP intolerance or unacceptance is not a recommen- TF observed that the balance of risks vs benefits for bariatric sur-
dation against (and does not preclude) discussion of surgical gery is highly dependent upon an individual patient’s OSA sever-
referral with patients with OSA, obesity, and adequate PAP use ity, symptoms, medical comorbidities, and selected surgical
if the health care provider deems it an appropriate management therapy but noted that a discussion of individualized risks and
discussion point. Other organizations, such as the National benefits is a standard component of the preoperative informed
Heart, Lung, and Blood Institute, recommend consideration of consent process. There is insufficient evidence in the literature
bariatric surgery for individuals suffering from obesity (class to compare the costs of bariatric surgery to nutritional care or
II/III, BMI ≥ 35 kg/m2) and OSA, regardless of PAP adherence untreated OSA. Because acceptability of surgical interventions
status.5 varies and there is little harm in discussing referral, based on their
The TF made a strong recommendation in favor of bariatric sur- combined clinical expertise the TF judged that most patients
gery referral based on moderate-quality evidence from 2 RCTs would generally be accepting of a discussion regarding referral.
and 28 observational studies that showed clinically meaningful The choice to pursue referral is expected to vary between patients
improvements in several critical outcomes, and the benefits of based on personal values, beliefs, and expectations for recovery
discussing referral over the harms of no treatment. time or pain with surgery.
The TF investigated the use of bariatric surgery to improve 1 or
more of the following critical outcomes: BP, QOL, sleep quality, Surgical treatment of patients to facilitate PAP use
OSA severity, and excessive sleepiness. The TF also considered Recommendation 3: We suggest that clinicians discuss referral
the risk of perioperative death as a critical outcome for decision- to a sleep surgeon with adults with OSA, BMI < 40 kg/m2, and
making, although the risk of other serious persistent adverse persistent inadequate PAP adherence due to pressure-related
events and motor vehicle accidents was also reviewed. The TF side effects as part of a patient-oriented discussion of adjunctive
identified 2 RCTs and 28 pre- vs postsurgical treatment observa- or alternative treatment options (CONDITIONAL).
tional studies comparing the use of bariatric surgery vs no
treatment that reported on 1 or more of the critical outcomes. Remarks: Available data suggest that upper airway surgery has
Meta-analyses demonstrated a clinically significant improve- a moderate effect in reducing minimum therapeutic PAP level and
ment in all critical outcomes. None of the studies reported on increasing PAP adherence. The decision to offer referral should be
the risk of perioperative death and motor vehicle accidents. based onthe clinician’s judgmentofa patient’s currentPAP adher-
The overall quality of evidence was moderate due to large ence and tolerance as well as the patient’s treatment preferences.
effect sizes in the observational studies and due to imprecision Low degrees ofnonadherence orminimal side effects may preclude
in the RCTs. The benefits of bariatric surgery in patients with obe- consideration of a referral. Referral may be informed by the pres-
sity and OSA include a reduction in AHI/RDI, BP, oxygen desa- ence of other surgically treatable conditions that contribute to
turation index (ODI), excessive sleepiness, BMI, snoring, and upper airway obstruction(eg, persistentnasal obstruction, chronic
optimal PAP level, and an increase in the minimum oxygen satu- tonsillitis, malocclusion). For patients within the BMI range of
ration during sleep (LSAT). Benefits demonstrated in literature 35–40kg/m2, discussionregardinga referraltobothsleep and bar-
are limited to patients considered appropriate for bariatric surgery iatricsurgeons (as per Recommendation 2) todiscuss management
by the treating surgeon and may not be representative of all options may be appropriate. The conditional recommendation to
discuss surgical referral with patients with a BMI < 40 kg/m2 is not assess differences in resource requirements for surgical referral
a recommendation against (and does not preclude) discussion vs inadequate PAP use. Because acceptability of surgical inter-
of surgical referral with patients with a BMI ≥ 40 kg/m2 if the ventions varies and there is little harm in offering referral, based
health care provider deems it an appropriate management discus- on their combined clinical expertise the TF judged that most
sion point, especially as some surgical therapies that reduce patients would generally be accepting of a discussion regarding
minimum therapeutic PAP level (eg, nasal surgery) are not antic- referral but that its clinical utility may be more limited in patients
ipated to be impacted by BMI. who are partially PAP adherent as opposed to those who are
completely untreated. The choice to pursue referral is expected
The TF made a conditional recommendation in favor of surgical
to vary between patients based on personal values, beliefs, and
referral based on very low-quality evidence from 7 observational
expectations for recovery time or pain with surgery.
studies showing clinically meaningful improvements in several
critical outcomes and the benefits of discussing referral over the
harms of persistent PAP-related side effects or inadequate use Surgical treatment as initial therapy in patients with a
that likely vary depending on the patient’s degree of use. major upper airway anatomical abnormality
The TF investigated the use of surgery as an adjunctive proce- Recommendation 4: We suggest that clinicians recommend
dure to facilitate the use of PAP by improving 1 or more of the fol- PAP as initial therapy for adults with OSA and a major upper
lowing critical outcomes: optimal PAP level, excessive airway anatomic abnormality prior to consideration of refer-
sleepiness, sleep quality, PAP adherence, snoring, and sleep- ral for upper airway surgery (CONDITIONAL).
related QOL. The TF also considered the risks of perioperative
Remarks: Major upper airway anatomic abnormalities con-
death and permanent dysphagia as critical outcomes for
sidered by the task force included tonsillar hypertrophy and max-
decision-making. The TF identified 7 observational studies com-
illomandibular abnormalities. While data suggest a clinically
paring pre- vs postsurgical treatment comparing 1 or more of the
significant benefit from surgical intervention in these popula-
critical outcomes. Meta-analyses of data extracted from these
tions, PAP should be recommended as initial treatment as it car-
studies were used to determine whether changes in these
ries minimal risk relative to surgery. The decision to discuss

outcomes were clinically significant. The results of the meta-
referral for initial surgical therapy should be based on the clini-
analyses demonstrated a clinically significant, moderate reduc-
cian’s judgment of the patient’s medical history as consideration
tion in optimal PAP level and a clinically significant, moderate
of initial surgical intervention may be justified in the setting of
improvement in PAP adherence with surgery. The incidence of
other surgical indications affecting upper airway patency
perioperative death and permanent dysphagia was not reported
(eg, chronic tonsillitis, malocclusion, abnormal lesion, or
in these studies. None of these studies reported on either QOL
growth). The conditional recommendation does not preclude dis-
or snoring.
cussion of surgical referral prior to the initial PAP trial if the
The overall quality of evidence was very low due to impreci-
health care provider deems it an appropriate management dis-
sion and risk of bias associated with observational studies. The
cussion point. Furthermore, this recommendation is for the initial
potential benefits of upper airway surgery as an adjunctive proce-
treatment of OSA and does not address management of patients
dure to facilitate effective PAP therapy include a reduction in
who have previously trialed PAP, as detailed in Recommenda-
optimal PAP level, excessive sleepiness, and AHI/RDI, as well
tions 1–3.
as an increase in PAP adherence and lowest oxygen saturation
(LSAT). Benefits demonstrated in the literature are limited to The TF made a conditional recommendation against surgical
patients considered appropriate for surgery by the treating sur- referral as initial treatment for OSA based on low-quality evi-
geon and may not be representative of all patients with PAP- dence from 2 RCTs and 15 observational studies, the balance of
related side effects or inadequate use. The potential harms of benefits to harms favoring PAP as an initial treatment over sur-
upper airway surgery as an adjunctive procedure include short- gery, and the benefits of discussing referral over the harms of
term discomfort that is expected during postoperative recovery PAP as an initial OSA therapy trial.
and is discussed during the preoperative informed consent pro- The TF investigated the use of surgery to improve 1 or more of
cess between the surgeon and patient. Surgery carries inherent the following critical outcomes: AHI/RDI, excessive sleepiness,
risks but based on their combined clinical experience and the sleep quality, LSAT, sleep-related QOL, snoring, and oxygen
moderate effects of surgery on PAP pressure requirements and desaturation. The TF also considered the risks of perioperative
adherence, the TF judged that the potential benefits of a discus- death and permanent dysphagia as critical outcomes for
sion regarding referral to a sleep surgeon for consideration of sur- decision-making, although the risk of other serious persistent
gery as an adjunctive procedure to facilitate PAP use may, in some adverse events and motor vehicle accidents was also reviewed.
patients, outweigh the potential harms of inadequate PAP-related The TF identified 2 RCTs and 15 pre- vs postsurgical treatment
side effects and adherence depending on their severity. If referral observational studies comparing the use of surgery vs no treat-
is discussed, the TF observed that the balance of risks vs benefits ment that reported on 1 or more of the critical outcomes. Studies
for upper airway surgery is highly dependent upon an individual including patients with prior PAP treatment were not excluded
patient’s OSA severity, symptoms, medical comorbidities, and from analysis as prior PAP exposure was not anticipated to rea-
selected surgical therapy but noted that a discussion of individu- sonably affect response to anatomy-altering surgery. Meta-
alized risks and benefits is a standard component of the preoper- analyses demonstrated a clinically significant reduction in AHI/
ative informed consent process. There are insufficient data to RDI, excessive sleepiness, snoring, and oxygen desaturation
index (ODI) and a clinically significant improvement in the techniques have proliferated over the last 10–15 years as surgeons
LSAT with surgery. There was no evidence to assess improve- have developed more effective and less morbid procedures better
ment in sleep-related QOL. The results of the meta-analyses tailored to the individual patient’s anatomy.
also demonstrated no clinically significant risk of permanent dys- Surgical treatments for OSA demonstrate large reductions in
phagia. The incidence of perioperative death was not reported in objective disease burden and patient-centered outcomes as com-
the studies. None of the studies reported on the risk of motor vehi- pared to no treatment. Patients who are intolerant or unaccepting
cle accidents. of PAP therapy should be informed that surgical management is
The overall quality of evidence was low due to imprecision and one of several viable alternative treatment options. The recommen-
risk of bias associated with the observational studies. The poten- dation to discuss referral does not preclude a patient-oriented dis-
tial benefits of upper airway surgery as an initial therapy include a cussion of other viable alternative treatment options (eg,
reduction in excessive sleepiness, snoring, systolic blood pres- mandibular advancement device, positional therapy, behavioral
sure, AHI/RDI, and ODI and an increase in LSAT. Benefits dem- changes)that may yieldfavorable benefitover nofurther treatment.
onstrated in the literature are limited to patients with a major The decision to undergo surgical treatment for OSA is a personal
anatomical obstruction considered appropriate for surgery by one, and the risk-benefit ratio will vary given an individual’s
the treating surgeon and may not be representative of all patients own values, personal preferences, anatomy, and medical history.
with OSA with similar anatomic findings. The potential harms of Health care providers are encouraged to consider these factors dur-
surgery include short-term discomfort that is expected during ing a discussion regarding referral, understanding that as the field
postoperative recovery and is discussed during the preoperative of surgery continues to rapidly evolve, the surgeon may ultimately
informed consent process. Additionally, potential persistent have the most current and comprehensive understanding of the evi-
long-term side effects have been reported including dysphagia, dence surrounding a patient’s individualized surgical indications,
taste alteration, mandibular paresthesia, aspiration, hemorrhage, risks, and potential outcomes. A patient-tailored discussion of
and globus pharyngeus, but the incidence of these is low. Given appropriate surgical risks and benefits is a standard component
that even low surgical risks are elevated as compared to the min- of the informed consent process conducted by the surgeon so that
imal risk of initial PAP therapy, the balance of benefits to harms a patient may make an informed decision. A discussion of the
favors PAP therapy as initial treatment over discussion of referral short-term andlong-term sideeffects of surgery arepart of that con-
for surgical evaluation. Nevertheless, the presence of major ana- versation. A potential limitation regarding this management option
tomical obstruction may tip the balance in favor of surgical refer- is access to a surgeon familiar with the variety of modern surgical
ral discussion depending on a patient’s upper airway medical techniques for OSA.Sleep surgeons havea responsibility toremain
history. Despite the low risk of surgical referral discussion, there current on new discoveries underlying the pathophysiologic mech-
is no harm in an initial trial of PAP therapy if other surgical indi- anisms of OSA, as these findings will likely inform an individual
cations are not present. Given that the intent of discussion of sleep patient’s surgical candidacy in the future. Close collaboration
surgery referral in this clinical scenario is consideration of upper with referring sleep medicine colleagues will help foster multidis-
airway surgery prior to any PAP trial, based on their combined ciplinary educational opportunities. Surgeons interested in treating
clinical expertise, the TF judged that the potential benefits of sur- thispatientpopulationshouldhavean appropriateunderstandingof
gical referral discussion in patients with major anatomical sleep medicine and modern surgical techniques.
obstruction do not exceed the potential benefits of an initial Upper airway surgery may have a moderate effect on decreas-
PAP trial for OSA in the absence of other medical conditions ing therapeutic PAP requirements (ie, optimal PAP level) and
affecting upper airway patency. Based on their combined clinical increasing PAP adherence although this estimate is based on a
expertise, the TF judged that most patients would generally be small number of uncontrolled observational studies. Considering
accepting of a discussion regarding referral for surgical evalua- the very low risk of surgical referral discussion and the informed
tion as there is little harm in the act of offering. Patient acceptance consent process, clinicians should consider discussing referral to
of surgical interventions will vary, and the clinical utility of refer- a surgeon with patients struggling with PAP tolerance and adher-
ral may be more limited in patients who are partially PAP adherence who have not responded adequately to previously attempted
ent. The choice to pursue referral is expected to vary between nonsurgical treatments.
patients based on personal values, beliefs, and expectations for Some patients are noted to have major anatomic obstruction on
recovery time or pain with surgery. initial evaluation, such as tonsillar hypertrophy or significant
maxillomandibular deficiencies. Despite the large effect size
seen with the appropriately indicated surgery, the high efficacy,
DISCUSSION low cost, and minimal harm of PAP therapy justify an initial trial
prior to consideration of surgical referral. It is important to
Positiveairwaypressure(PAP)isrecognizedasthemostefficacious remember that additional patient history (eg, chronic tonsillitis,
treatment for the majority of OSA outcomes if worn consistently, malocclusion) may justify discussion of a surgical referral prior
but a growing body of literature confirms that a substantial portion to an initial medical therapy trial. Patients with major anatomic
of patients do not accept or tolerate it as a treatment option.6–9 Poor obstruction who refuse PAP therapy should discuss referral for
adherence to PAP therapy likely compromises patients’ ability to surgical evaluation with their health care provider.
derive all potential subjective and objective benefits. A variety of Weight loss can have a substantial impact on OSA disease bur-
alternatives to PAP for OSA treatment exist, including surgical den in obese patients. Bariatric surgery is the most effective ther-
interventions. New diagnostic tools and improved surgical apy for weight loss in patients with class II or III obesity.
Discussion regarding bariatric surgery referral should be consid- 7. Jacobsen AR, Eriksen F, Hansen RW, et al. Determinants for adherence to continuous
ered in this population, which may be considered in parallel with positive airway pressure therapy in obstructive sleep apnea. PLoS One. 2017;12(12):
e0189614.
medical weight loss options as well as other OSA treatments. Dur-
8. Kohler M, Smith D, Tippett V, Stradling JR. Predictors of long-term compliance with
ing the consultation, the surgeon will discuss lifestyle changes continuous positive airway pressure. Thorax. 2010;65(9):829–832.
necessary to be successful with bariatric surgery. Ultimately, 9. Virk JS, Kotecha B. When continuous positive airway pressure (CPAP) fails. J Thorac
patients will have to agree to major lifestyle changes to be suc- Dis. 2016;8(10):E1112–E1121.
cessful with bariatric surgery, and some are not ready for these
changes. Although not specifically included in this review, avail- ACKNOWLEDGMENTS
able data suggest bariatric surgery can reduce positive airway
pressure requirements and improve PAP adherence. Referral The task force acknowledges the early contributions of Edward Weaver, MD, MPH
(University of Washington Medical Center, Seattle, WA), who assisted with the
may be limited by proximity to a bariatric surgery center, and development of the PICO questions and project charter. The task force also thanks
varying insurance coverages may impact patient access to this Ofer Jacobowitz, MD, PhD (Icahn School of Medicine at Mount Sinai, New York, NY);
treatment option. A growing evidence base from patients outside Eric J. Kezirian, MD, MPH (Keck School of Medicine of University of Southern
the US with class I obesity and access to bariatric surgery suggests California, Los Angeles, CA); Reena Mehra, MD, MS (Cleveland Clinic, Cleveland,
significant potential health benefits in this population as well. The OH); and Sanjay R. Patel, MD (University of Pittsburgh Medical Center, Pittsburgh, PA)
for serving as external reviewers of the document and providing valuable feedback.
potential for surgical weight loss benefits in patients with OSA
and body mass index less than 35 kg/m2 will require further eval- This guideline was endorsed by the American Society for Metabolic and Bariatric
uation in the coming years. Surgery and the Alliance of Sleep Apnea Partners. The American Academy of
Otolaryngology–Head and Neck Surgery affirmed the value of this guideline.
REFERENCES
SUBMISSION & CORRESPONDENCE INFORMATION
1. Aurora RN, Casey KR, Kristo D, et al. American Academy of Sleep Medicine. Practice Submitted for publication August 3, 2021
parameters for the surgical modifications of the upper airway for obstructive sleep Submitted in final revised August 3, 2021
apnea in adults. Sleep. 2010;33(10):1408–1413. Accepted for publication August 3, 2021

2. Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea Address correspondence to: David Kent, MD, Department of Otolaryngology, Vanderbilt
for surgical consultation: an American Academy of Sleep Medicine systematic University, 3601 21st Avenue South, Nashville, TN 37232;
review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12): Email: [email protected]
2507–2531.
3. Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel SR, Harrod CG. Treatment of adult
obstructive sleep apnea with positive airway pressure: an American Academy of Sleep DISCLOSURE STATEMENT
Medicine clinical practice guideline. J Clin Sleep Med. 2019;15(2):335–343.
The development of this paper was funded by the American Academy of Sleep
4. Morgenthaler TI, Deriy L, Heald JL, Thomas SM. The evolution of the AASM clinical
Medicine (AASM). Dr. David Kent is listed as an inventor on U.S. and international
practice guidelines: another step forward. J Clin Sleep Med. 2016;12(1):129–135.
patent applications regarding surgical treatments for OSA owned and licensed by
5. National Institutes of Health; National Heart, Lung, and Blood Institute; North American Vanderbilt University (VU) to Nyxoah SA. Dr. Kent receives a portion of any licensing
Association for the Study of Obesity. The Practical Guide: Identification, Evaluation, and revenues as per standard VU technology transfer policy. The licensed treatment
Treatment of Overweight and Obesity in Adults. NIH Publication No. 00-4084. https:// methodologies do not currently exist in prototype or commercial form and are not
www.nhlbi.nih.gov/files/docs/guidelines/prctgd_c.pdf. Accessed August 17, 2021. represented in the surgical literature reviewed by the TF. The licensing agreement was
6. Cistulli PA, Armitstead J, Pepin JL, et al. Short-term CPAP adherence in completed in early 2021, after completion of the initial clinical practice guideline,
obstructive sleep apnea: a big data analysis using real world data. Sleep Med. supporting systematic review, and public comment period. Mr. Harrod is employed by
2019;59:114–116. the AASM. The other authors report no conflicts of interest.
Research
JAMA | Preliminary Communication
Effect of Multilevel Upper Airway Surgery vs Medical Management

on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness
Among Patients With Moderate or Severe Obstructive Sleep Apnea
The SAMS Randomized Clinical Trial
Stuart MacKay, MD; A. Simon Carney, DM; Peter G. Catcheside, PhD; Ching Li Chai-Coetzer, MD, PhD;
Michael Chia, MD; Peter A. Cistulli, MD, PhD; John-Charles Hodge, MD; Andrew Jones, MD;
Billingsley Kaambwa, PhD; Richard Lewis, MD; Eng H. Ooi, MD, PhD; Alison J. Pinczel, PhD; Nigel McArdle, MD;
Guy Rees, MD; Bhajan Singh, MD, PhD; Nicholas Stow, MD; Edward M. Weaver, MD, MPH;
Richard J. Woodman, PhD; Charmaine M. Woods, PhD; Aeneas Yeo, MD; R. Doug McEvoy, MD
Editorial page 1161

IMPORTANCE Many adults with obstructive sleep apnea (OSA) use device treatments Author Audio Interview
inadequately and remain untreated.
Supplemental content
OBJECTIVE To determine whether combined palatal and tongue surgery to enlarge or stabilize
CME Quiz at
the upper airway is an effective treatment for patients with OSA when conventional device
jamacmelookup.com
treatment failed.
DESIGN, SETTING, AND PARTICIPANTS Multicenter, parallel-group, open-label randomized

clinical trial of upper airway surgery vs ongoing medical management. Adults with
symptomatic moderate or severe OSA in whom conventional treatments had failed were
enrolled between November 2014 and October 2017, with follow-up until August 2018.
INTERVENTIONS Multilevel surgery (modified uvulopalatopharyngoplasty and minimally

invasive tongue volume reduction; n = 51) or ongoing medical management (eg, advice on
sleep positioning, weight loss; n = 51).
MAIN OUTCOMES AND MEASURES Primary outcome measures were the apnea-hypopnea
index (AHI; ie, the number of apnea and hypopnea events/h; 15-30 indicates moderate and
>30 indicates severe OSA) and the Epworth Sleepiness Scale (ESS; range, 0-24; >10 indicates
pathological sleepiness). Baseline-adjusted differences between groups at 6 months were
assessed. Minimal clinically important differences are 15 events per hour for AHI and 2 units
for ESS.
RESULTS Among 102 participants who were randomized (mean [SD] age, 44.6 [12.8] years; 18
[18%] women), 91 (89%) completed the trial. The mean AHI was 47.9 at baseline and 20.8 at
6 months for the surgery group and 45.3 at baseline and 34.5 at 6 months for the medical
management group (mean baseline-adjusted between-group difference at 6 mo, −17.6
events/h [95% CI, −26.8 to −8.4]; P < .001). The mean ESS was 12.4 at baseline and 5.3 at 6
months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical
management group (mean baseline-adjusted between-group difference at 6 mo, −6.7 [95%
CI, −8.2 to −5.2]; P < .001). Two participants (4%) in the surgery group had serious adverse
events (1 had a myocardial infarction on postoperative day 5 and 1 was hospitalized for
observation following hematemesis of old blood).
CONCLUSIONS AND RELEVANCE In this preliminary study of adults with moderate or severe
OSA in whom conventional therapy had failed, combined palatal and tongue surgery,
compared with medical management, reduced the number of apnea and hypopnea events
and patient-reported sleepiness at 6 months. Further research is needed to confirm these
findings in additional populations and to understand clinical utility, long-term efficacy, and
safety of multilevel upper airway surgery for treatment of patients with OSA. Author Affiliations: Author
affiliations are listed at the end of this
TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry: ACTRN12614000338662 article.
Corresponding Author: Stuart
MacKay, MD, Illawarra ENT
Head and Neck Clinic, Suites 1&2,
8-10 Victoria St, Wollongong,
JAMA. 2020;324(12):1168-1179. doi:10.1001/jama.2020.14265 NSW 2500, Australia (sgmackay@
Published online September 4, 2020. ozemail.com.au).
1168 (Reprinted) jama.com
© 2020 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 01/25/2022

Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea Preliminary Communication Research
A
dult obstructive sleep apnea (OSA) is associated with
numerous adverse effects if left untreated, including Key Points
daytime sleepiness, reduced quality of life, increased
Question Is multilevel airway surgery effective in adults with
cardiovascular morbidity and mortality, and an increased risk moderate or severe obstructive sleep apnea (OSA) who cannot
of motor vehicle crashes. 1-3 A narrow or unstable upper tolerate or adhere to device use?
airway4 predisposes to episodes of complete or partial air-
Findings In this randomized clinical trial of 102 adults, modified
flow reduction (ie, obstructive apnea or hypopnea) during
uvulopalatopharyngoplasty and radiofrequency in saline tongue
sleep when pharyngeal dilator muscle tone falls. Continuous reduction, compared with ongoing medical management,
positive airway pressure (CPAP) delivered by mask, or jaw significantly improved the apnea-hypopnea index (mean
advancement with an oral appliance, can alleviate obstruc- baseline-adjusted between-group difference, −17.6 events per
tion; however, many patients either refuse these therapies, hour of sleep) and patient-reported sleepiness (mean
use them inconsistently, or (as in the case of oral appliances) baseline-adjusted between-group difference in Epworth
Sleepiness Scale, −6.7; range, 0-24; higher score indicates greater
achieve suboptimal efficacy, leaving at least 50% of patients
sleepiness) at 6 months.
without effective treatment5,6 and exposed to the risk of seri-
ous long-term morbidity. Surgical treatments aim to enlarge Meaning In this preliminary study of adults with moderate or
and stabilize the upper airway and may provide an option for severe OSA who failed conventional treatment, combined palatal
and tongue surgery improved patient-reported sleepiness and
patients in whom conventional medical treatment had
polysomnographic measures of OSA severity at 6 months,
failed.7 However, to date, there have been few randomized although further research is needed to confirm these findings in
trials evaluating the benefits and complications of these sur- additional populations and to evaluate the safety, clinical utility,
gical procedures compared with controls,8-11 and most have and long-term efficacy of multilevel upper airway surgery for
tested surgical treatment at a single level of the upper airway treatment of individuals with OSA.
in highly select patients.8,9,11
The Sleep Apnea Multilevel Surgery (SAMS) trial was a ran-
domized clinical trial of a standardized surgical procedure to or psychiatric comorbidities, were judged to be a high anes-
relieve both retropalatal and retrolingual obstruction in adult thetic risk, were pregnant, or had specific anatomical contra-
patients who had moderate or severe symptomatic OSA for indications to the intended surgery (eg, severe palatal scar-
whom conventional device treatment had failed. The pri- ring from previous surgery or severe retrognathia). A full
mary hypothesis was that surgery would be more effective than description of the inclusion and exclusion criteria is provided
ongoing medical management in improving OSA, as mea- in eTable 1 in Supplement 2.
sured by a decrease in the frequency of sleep apneas and hy- After eligibility was confirmed, participants were ran-
popneas and a reduction in subjective daytime sleepiness. domly assigned to receive either surgery or ongoing medical
management at an independent central location. A minimi-
zation program (MinimPy 0.3)13 incorporating biased-coin
minimization (base probability, 0.7; marginal balance; 1:1 al-
Methods location ratio) was used to ensure balance between variables
Ethical Approval and Informed Consent that had the potential to affect outcomes, namely, study site,
Each of the participating sites had human research ethics ap- sex, age (<50, ≥50 years), AHI (<50, ≥50 events/h), and body
proval to conduct the study. An independent data and safety mass index (<28, ≥28). Enrollment began in August 2014, but,
monitoring board regularly reviewed data on serious and non- because of slow recruitment, the protocol was amended in
serious adverse events and study quality. Written informed January 2016 after reaching 30% of the recruitment target (31
consent was obtained from each participant. of 102 planned participants) to relax the body mass index ex-
clusion threshold from greater than 35 to greater than 38 and
Study Design and Patients lower the AHI inclusion requirement from greater than 20 to
This was a multicenter, parallel-group, open-label, random- greater than 15 events per hour.
ized clinical trial of upper airway surgery vs ongoing medical
management conducted across 6 Australian academic cen- Interventions
ters. The study reporting conforms to CONSORT guidelines for The surgery intervention (eFigure in Supplement 2) con-
randomized trials. The full protocol and statistical analysis plan sisted of a modified uvulopalatopharyngoplasty to widen and
for this trial are available in Supplement 1. The rationale and stabilize the velopharynx and 7 to 9 submucosal insertions of
design of the study has been published previously.12 a radiofrequency-in-saline wand to reduce tongue volume as
Eligible adults were aged 18 to 70 years with moderate or previously described.14 A training workshop was conducted
severe OSA (defined as apnea-hypopnea index [AHI] of 15-30 to standardize the surgical techniques among the 7 participat-
and >30 events/h of sleep), body mass index less than 38, and ing surgeons.12 Ongoing medical management consisted of a
Epworth Sleepiness Scale (ESS) greater than 8 (range, 0-24; range of evidenced-based treatments as appropriate (eg, weight
higher scores indicate greater sleepiness) in whom medically loss, alcohol reduction, sleep posture modification, medical
supervised attempts to use CPAP and, when deemed appro- management of nasal obstruction) and assistance with retrial
priate, a mandibular advancement device failed or were re- of CPAP or mandibular advancement device therapies if par-
fused. Patients were excluded if they had significant medical ticipants were willing.
jama.com (Reprinted) JAMA September 22/29, 2020 Volume 324, Number 12 1169

Research Preliminary Communication Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea
Assessments 15-30, moderate OSA; and greater than 30, severe OSA (a change
The follow-up assessment was scheduled for 6 months after of ≥15 is considered the minimal clinically important
the surgical intervention for the surgery group and for 6 months difference).2 The ESS evaluates patient self-reported sleepi-
after the date of baseline assessments for the ongoing medi- ness (range, 0-24; higher scores indicate greater severity; >10
cal management group. All participants were assessed by a phy- signifies pathological sleepiness; change of 2 indicates the mini-
sician certified in sleep medicine at baseline and at 1, 3, and 6 mal clinically important difference).20
months. Participants in the surgery group were also assessed Secondary outcomes included the following polysomnog-
by a surgeon before surgery; at the time of surgery; and 1, 3, raphy measures of OSA severity and sleep quality: the per-
and 6 months after surgery (eTable 2 in Supplement 2). Vali- centage of participants with AHI less than 10, the apnea in-
dated questionnaires measured patient- and partner- dex, 3% and 4% oxygen desaturation indices, the lowest oxygen
reported outcomes at baseline and each follow-up. Demo- saturation in sleep, percentage of sleep time with oxygen satu-
graphic information, medical information, OSA treatments ration <90%, AHI and lowest oxygen saturation in supine and
used, and body mass index were measured for all enrolled par- nonsupine sleep positions, arousal index, and percentages of
ticipants at baseline and at each follow-up visit. Information total sleep time spent in sleep stages nonrapid eye movement
on race was collected because severity of OSA can vary by race, stage 1 (N1) through N3 and in rapid eye movement (REM) sleep
and it was defined by participants using an open-ended ques- (mean available age-appropriate normal values: lowest oxy-
tionnaire. Friedman stage was determined at baseline by di- gen saturation, 90.5% [95% CI, 89.3%-91.7%]; arousal index,
rect visualization of tongue position, tonsil size, and measure- 12.5 [95% CI, 10.7-14.2]; N1 sleep, 8.0% of sleep time [95% CI,
ment of body mass index. Stages I through IV denote the 6.9%-9.2%]; N2 sleep, 52.2% of sleep time [95% CI, 50.6%-
presence of anatomical features previously considered to range 53.8%]; N3 sleep, 20.4% of sleep time [95% CI, 18.5%-22.2%];
from the most to least favorable for upper airway soft tissue REM sleep, 19.3% of sleep time [95% CI, 18.2%-20.3%])21; there
surgery: stage I indicates low tongue position with moderate are no agreed minimal clinically important difference values
or severe tonsil enlargement; stage II, low tongue/no or mi- for these parameters. Other secondary outcomes were objec-
nor tonsil enlargement or high tongue position/moderate or tive daytime sleepiness, measured with the multiple sleep la-
severe tonsil enlargement; stage III, high tongue position/no tency test and expressed as mean sleep latency in minutes (val-
or minor tonsil enlargement; and stage IV, body mass index ues below 10 minutes signify an increased propensity to fall
greater than 40 or skeletal deformities (eg, micrognathia or asleep; the minimal clinically important difference is 1
midface hypoplasia).15 The exclusion criterion for this study minute2); partner-reported patient snoring, measured with the
precluded the recruitment of patients with Friedman stage IV. Snoring Severity Scale22 (range, 0-9; higher scores indicate
All adverse events and postsurgery symptoms, regardless of more intense snoring; no agreed minimal clinically impor-
their severity, were systematically recorded at each of the tant difference); sleep-specific quality of life, measured with
follow-up appointments.12 Serious adverse events were based the Functional Outcomes of Sleep Questionnaire-3023 (range,
on the guidelines adopted by the International Conference on 5-20; higher scores indicate better functional status; ≥17.9 is
Harmonization of Good Clinical Practice.16 considered normal; a score change of 1 is considered to be the
Polysomnography, multiple sleep latency tests, and blood minimal clinically important difference24); generic health-
pressure measurements occurred at baseline and 6 months. related quality of life25 and self-rated health status,26 mea-
The sleep tests were scored according to the American Acad- sured with the EuroQol Group 5-dimension 5-level (EQ-5D-
emy of Sleep Medicine 2007 manual17 at a central sleep labo- 5L) instrument (utility index range, −0.594 to 125; higher scores
ratory (Adelaide Institute for Sleep Health) by 2 experienced indicate better quality of life; score change ranging from 0.03-
sleep technicians who were blinded to patient treatment al- 0.52 are considered the minimal clinically important differ-
location. For the AHI, the alternate criteria was used with hy- ences in other diseases there is no minimal clinically impor-
popnea defined as 50% reduction in airflow for at least 10 sec- tant difference established for OSA27]) and EQ visual analogue
onds and associated with either a 3% oxyhemoglobin scale (range, 0 [worst possible health] to 100 [best possible
desaturation or a cortical arousal.17 The multiple sleep la- health]; score changes ranging from 3.5-10.1 considered to be
tency test consisted of 5 daytime 20-minute sleep opportuni- the minimal clinically important differences in other
ties spaced 2 hours apart from which mean sleep latency was diseases28,29); the Glasgow Benefit Inventory,30 which was
calculated as the mean time to sleep onset after lights out.18 completed by participants randomized to the surgery group
Office and 24-hour ambulatory blood pressure measure- 6 months after the surgical procedure (change in quality of life
ments were obtained at baseline and again at 6 months. It was following surgery is graded from −100 [poorest outcome] to
not possible to blind the research staff assisting with the other 100 [best outcome], with 0 indicating no change; no reported
evaluations. Further details on patient assessments are pro- minimal clinically important difference); and office and am-
vided in Supplement 2. bulatory 24-hour, daytime, and nighttime blood pressure (mini-
mal clinically important difference for 24-hour ambulatory
Study Outcomes blood pressure is 1 mm Hg2). Some other outcomes were col-
The primary study outcomes were the baseline-adjusted dif- lected to provide mechanistic insights (eg, anthropometric
ferences between groups in the AHI and ESS19 at 6 months. The measures, adherence to other OSA therapies). Data on cost,
AHI reports the number of apnea and hypopnea events per hour imaging, and nasendoscopic findings were collected but are
of sleep, with 0 to 5 signifying no OSA; 5 to 14, mild OSA; not reported in this article. Serious adverse event rates were
1170 JAMA September 22/29, 2020 Volume 324, Number 12 (Reprinted) jama.com

scored as the percentage of patients with 1 or more serious ad-

Figure 1. Recruitment, Randomization, and Flow of Participants
verse events. in a Study of the Effect of Upper Airway Surgery vs Ongoing Medical
Management on Patients With Obstructive Sleep Apnea
Statistical Analysis
Based on data from a preliminary study,12,14 a sample size of 612 Patients assessed for eligibility
51 participants per group was estimated to provide at least 80%
power to detect superior reductions in AHI and ESS with sur- 510 Excluded
gery compared with medical management as demonstrated by 449 Did not meet inclusion
criteria
the lower limit of the 95% CI for the difference in mean val- 54 Refused to participate
ues at 6 months being at least 20 events per hour for the AHI 7 Trial was full
and 3 units for the ESS.12 These differences are greater than the
minimal clinically important differences of 15 events per hour 102 Randomized
for the AHI and 2 units for the ESS to account for the cost and
potential morbidity of surgery, a concept termed sufficiently
important difference.31 51 Randomized to the surgery group 51 Randomized to the ongoing
50 Underwent surgery medical management group
The sample size was based on the ESS primary outcome be- 1 Withdrew consent before
cause it required a larger sample than the AHI primary out- surgery
come. The a priori sufficiently important31 superiority margin

was set to 3 in ESS change between the groups at 6 months, and 2 Lost to follow-up 8 Lost to follow-up
1 Withdrew consent 4 Withdrew consent
an SD of 5 was estimated based on the preliminary study.12,14 1 Lost contact 4 Lost contact
For the sample size estimation, the t test was used at a 2-sided
α level of .05 for significance and power of 80% (β = 0.20) and 50 Included in analysis 49 Included in analysis
provided an adjustment in case of a nonnormal distribution, 1 Withdrew before data collection 2 Withdrew before data collection
and was excluded from analysis and were excluded from analysis
yielding the sample size of 102.12 The use of a mixed-effects
model to account for missing data further increased statistical
power compared with that estimated with the t test. ary end points should be interpreted as exploratory. Al-
Descriptive data are presented using mean and SD for nor- though it was not prespecified in the trial protocol or statisti-
mally distributed continuous data and frequency and percent- cal analysis plan (Supplement 1), it was considered important
age for categorical data. Within-group changes and between- that both primary outcomes (ie, nighttime respiratory distur-
group differences are presented with 95% CIs. Participants were bance [AHI] and self-reported sleepiness [ESS]) would need to
analyzed according to their randomization group. All partici- decrease significantly to demonstrate clinical efficacy.
pants with data at baseline were included in the analysis, with Post hoc sensitivity analyses were conducted to explore
missing data assumed to be missing at random and any poten- whether there was significant heterogeneity of treatment ef-
tial bias in estimated effects accounted for by the use of mixed- fect among the 7 surgeons by including a group × surgeon in-
effects models. For all continuous outcome variables, the ef- teraction term in the models for the 2 primary outcomes (AHI
fect of treatment was assessed on the basis of the difference in and ESS). Five of the 6 sites had only 1 assessing surgeon and
the 6-month follow-up values between groups after adjust- the other site had 2 assessing surgeons. To assess whether there
ment for baseline values. Differences were obtained using lin- was any clustering effect of participants within surgeon, an ad-
ear mixed-effects models with a Poisson link distribution func- ditional random intercept for surgeon was used in the mixed-
tion used for those variables for which the outcome could be effects models. In addition, because inclusion criteria were al-
interpreted as a count and for which the distribution of either tered when enrollment was approximately 30% complete to
the level 1 or level 2 residuals were nonnormally distributed. The change AHI from greater than 20 to greater than 15 and body
relevant outcome was the dependent variable and fixed- mass index from less than or equal to 35 to less than or equal
effects terms for the intervention group, visit (baseline or 6 to 38, a post hoc sensitivity analysis was conducted to deter-
months), and an interaction between group and visit, which was mine whether results were different among participants who
interpreted as the intervention effect. The participant ID was met the original inclusion criteria for the study.
included as a random intercept term. Binary variables were ana-
lyzed with the Fisher exact test. Serious adverse event rate be-
tween-group differences and 95% CIs were calculated with the
Wilson procedure without correction for continuity. All data
Results
were analyzed using Stata, version 15.0 (StataCorp). Study Overview
Effect estimates are reported as mean (95% CI). Hypoth- A total of 612 participants were screened for eligibility (Figure 1):
esis testing was 2-sided and P < .05 was considered statisti- 102 met the eligibility criteria and were enrolled in the study
cally significant. Corrections for multiple comparisons were between November 2014 and October 2017, with the last
not applied to the 2 primary outcomes because they were con- follow-up visit conducted in August 2018. Eleven partici-
sidered independent and fall into distinct families of equally pants did not complete the study (3 in the surgery group
important outcomes. Because of the potential for type I error and 8 in the ongoing medical management group). For the
due to multiple comparisons, findings for analyses of second- 2 primary outcomes, there was missing data for the ESS for

medical management group and for 1 in the surgery group, each

Table 1. Baseline Characteristics of Randomized Participants in a Study
of the Effect of Upper Airway Surgery vs Ongoing Medical Management of whom withdrew before baseline measurements. Baseline
on Patients With Obstructive Sleep Apnea (OSA) characteristics of trial participants (Table 1) showed that the 2
groups were well matched in terms of demographic and clini-
Medical
Surgery group management group cal characteristics. Participants were predominantly middle-
Characteristic (n = 51) (n = 51)
aged men with overweight or obesity and severe OSA. Fried-
Demographics
man stages were reasonably evenly distributed within each
Age, mean (SD), y 42.7 (12.8) 46.4 (12.6)
group. Further details on the study participants and the sur-
Sex, No. (%)
gical intervention are provided in eTable 3 to eTable 6 in
Men 41 (80) 43 (84) Supplement 2.
Women 10 (20) 8 (16)
Race, No. (%) Study Outcomes
White 44 (86.3) 46 (90.2) Primary Outcomes
Othera 7 (13.7) 5 (9.8) There was a statistically significantly greater improvement from
Apnea-hypopnea index, 47.9 (23.1) 45.3 (23.9) baseline to 6 months in the AHI in the surgery group (47.9 vs
mean (SD)b
20.8) than in the ongoing medical management group (45.3 vs
Epworth Sleepiness Scale, 12.4 (3.6) 11.1 (4.7)
mean (SD)c 34.5) (mean baseline-adjusted between-group difference, −17.6
Anatomy events/h of sleep [95% CI, −26.8 to −8.4]; P < .001) and in the
Friedman stage, No. (%)d ESS in the surgery group (12.4 vs 5.3) compared with the on-
I (best) 14 (27) 10 (20) going medical management group (11.1 vs 10.5) (mean baseline-
II 23 (45) 21 (41) adjusted between-group difference, −6.7 [95% CI, −8.2 to −5.2];
III (worst) 14 (27) 20 (39) P < .001) (Figure 2 and Table 2).
Body mass index, mean (SD)
Men 30.1 (4.0) 30.0 (3.6)
Secondary Outcomes
Although only a minority of participants achieved complete
Women 33.3 (2.8) 26.6 (2.9)
or near-complete OSA resolution (ie, AHI <10), the percent-
Previous OSA treatment, No. (%)
age of participants who achieved resolution was significantly
Tried CPAP 38 (75) 37 (73)
higher in the surgery group than the ongoing medical man-
Refused CPAP 13 (25) 14 (27)
agement group (26% vs 8%; mean baseline-adjusted
Tried mandibular advancement 16 (31) 12 (24)
device between-group difference, 18% [95% CI, 4%-32%]; P = .01)
Comorbidities, No. (%)e (Table 2). Results of analyses of other AHI cutoff values are
Respiratory diseases 12 (23.5) 6 (11.8) shown in eTable 7 in Supplement 2. Surgery had a similar
Cardiometabolic diseases 10 (19.6) 20 (39.2) favorable significant effect on supine AHI (mean baseline-
Other chronic disorders 10 (19.6) 7 (13.7)
adjusted between-group difference, −18.7 events/h [95% CI,
−31.1 to −6.3]; P = .003) and nonsupine AHI (mean baseline-
Abbreviations: CPAP, continuous positive airway pressure.
adjusted between-group difference, −18.4 events/h [95% CI,
a
Race “other” was self-reported by 12 participants as Asian (n = 3), Australian
−29.5 to −7.3]; P = .001) (eTable 7 in Supplement 2). Com-
Aboriginal (n = 2), Indian (n = 2), Hispanic/Latino (n = 1), Seychelles (n = 1),
Sri Lankan (n = 1), Greek (n = 1), and mixed (n = 1). pared with participants in the ongoing medical management
b
The apnea-hypopnea index reports the number of apnea and hypopnea group, participants in the surgery group had significantly
events per hour of sleep (0-5 indicates no OSA; 5-14, mild OSA; 15-30, improved sleep quality in terms of lower frequency of arous-
moderate OSA; and >30, severe OSA; a change of ⱖ15 is considered the als (mean baseline-adjusted between-group difference, −11.2
minimal clinically important difference2). To take account of the cost and
potential morbidity of the surgical intervention, a sufficiently important
events/h of sleep [95% CI, −14.9 to −7.5]; P < .001), less light
difference value of 20 was adopted. sleep (N1 sleep: mean baseline-adjusted between-group dif-
c
Epworth Sleepiness Scale19 evaluates sleepiness (range, 0-24; higher scores ference, −3.9% of sleep time [95% CI, −5.5% to −2.3%];
indicate greater severity; score >10 is considered to signify pathological P < .001), and improved sleep oxygenation (3% oxygen
sleepiness; a change of 2 is considered the minimal clinically important
desaturation index: baseline-adjusted between-group differ-
difference20). To take account of the cost and potential morbidity of the
surgical intervention, the sufficiently important difference of 3 was adopted. ence, −13.5 events/h of sleep [95% CI, −20.0 to −7.1]; P < .001)
d
Friedman stage incorporates palate size and tongue position, with stage I (Table 2 and eTable 7 in Supplement 2), although several of
being most favorable and stage IV least favorable (Friedman stage IV definition these parameters remained abnormal at study completion.
includes body mass index >40, which was an exclusion criterion for this study). Multiple sleep latency test findings were within normal limits
e
Comorbidities were classified as respiratory diseases (asthma and chronic at baseline and showed no significant between-group differ-
obstructive pulmonary disease), cardiometabolic diseases (diabetes, coronary
ence in mean sleep onset latency at 6 months (mean
heart disease, atrial fibrillation, hypertension, stroke), and chronic diseases
(arthritis and chronic pain syndrome). baseline-adjusted between-group difference, 0.6 min [95%
CI, −1.3 to 2.5]; P = .54). At 6 months, there were statistically
significant mean between-group differences favoring surgery
2 participants in the medical management group and 1 par- for partner-reported snoring (Snoring Severity Index: −4.0
ticipant in the surgery group at both baseline and 6 months. [95% CI, −4.9 to −3.1]; P < .001), sleep-specific quality of life
There was missing data for the AHI for 2 participants in the (Functional Outcomes of Sleep Questionnaire score: 3.4 [95%

Figure 2. Apnea-Hypopnea Index (AHI) and Epworth Sleepiness Scale (ESS) Outcomes in a Study of the Effect of Upper Airway Surgery vs Ongoing
Medical Management on Patients With Obstructive Sleep Apnea (OSA)
A AHI
Surgery group Medical management group
120 50
100
25
Change from baseline to 6 mo

80
0
60
AHI
40
–25
20
–50
0
–20 –75
Baseline 6 51 1 1 50 Baseline 6 Surgery Medical
mo mo management
Patients
B ESS
Surgery group Medical management group
25 5
20 0
Change from baseline to 6 mo

15 –5
ESS
10
–10
5
–15
0
–20
Baseline 6 50 1 1 49 Baseline 6 Surgery Medical
mo mo management
Patients
The ends of the boxes in the boxplots are located at the first and third quartiles, ongoing medical management group. A, The AHI indicates the number of apnea
with the black line in the middle illustrating the median. The dashed line and hypopnea events per hour of sleep (0-5 is classified as normal; 5-14, mild
signifies the mean. Whiskers extend to the upper and lower adjacent values, the OSA; 15-30, moderate OSA; >30, severe OSA; a change of at least 15 is
location of the furthest point within a distance of 1.5 interquartile ranges from considered clinically meaningful and can move a patient 2 levels from severe to
the first and third quartiles. The parallel line plot contains 1 vertical line for each mild with established benefit for health2). B, The ESS19 evaluates sleepiness
patient which extends from their baseline value to their 6-month value.40 (range, 0-24; higher scores indicate greater severity; score >10 signifies
Descending lines indicate an improvement in symptoms. Baseline values are pathological sleepiness; a change of 2 is the minimally important clinical
placed in ascending order for the surgery group and descending order for the difference20).
CI, 2.5-4.4]; P < .001), and self-rated general health status Very few participants attempted to use CPAP (n = 7) or a
(EQ visual analog scale score: 10.5 [95% CI, 5.6-15.4]; mandibular advancement device (n = 1) during the trial, and
P < .001), but were not statistically significantly different for there was no significant weight loss in either study group
general health-related quality of life (EQ-5D-5L score: 0.06 (between-group difference, −1.2 kg [95% CI, −2.8 to 0.4]; P = .14)
[95% CI, 0.00-0.12]; P = .054) (Table 2). Participants in the or change in health behaviors (eTable 7 in Supplement 2).
surgery group identified specific health benefits from the
surgical procedures (mean [SD] Glasgow Benefit Inventory, Post Hoc Sensitivity Analyses
32.1 [22.8]) (eTable 7 in Supplement 2). Mean blood pressure There was no significant difference in treatment effect among
values were normal at baseline and showed no significant surgeons for the AHI (χ 25 = 5.66; P = .34) or the ESS (χ 25 = 4.51;
between-group difference at 6 months (in-office systolic P = .48). There was also no significant difference in the treatment
blood pressure: −2.5 [95% CI, −7.1 to 2.2]; P = .30; in-office effects after incorporating a random intercept for surgeons into
diastolic blood pressure: −3.9 [95% CI, −8.1 to 0.3]; P = .07) each model or when using data only for participants who met
(Table 2 and eTable 7 in Supplement 2). the original inclusion criteria (eTable 8 in Supplement 2).

Table 2. Estimated Treatment Effects in the Primary and Secondary Outcomes in a Study of the Effect of Upper Airway Surgery vs Ongoing Medical
Management on Patients With Obstructive Sleep Apnea
Baseline-adjusted
difference
of surgery
Surgery group (n = 50) Medical management group (n = 49) vs medical
Change from Change from management
Baseline, 6 mo, baseline, Baseline, baseline, group,
Outcome mean (SD) mean (SD) mean (95% CI) mean (SD) 6 mo, mean (SD) mean (95% CI) mean (95% CI)a P valueb
Primary outcomes
Apnea-hypopnea 47.9 (23.1) 20.8 (18.4) −27.4 45.3 (23.9) 34.5 (23.0) −9.8 −17.6 <.001
indexc (−33.8 to –21.0) (−16.5 to −3.1) (−26.8 to −8.4)
Apnea-hypopnea 43.2 15.6 34.1 26.7 (17.1 to 48.0)
index, (28.7 to 74.7) (9.8 to 24.8) (25.0 to 61.8)
median (IQR)
Epworth Sleepiness 12.4 (3.6) 5.3 (3.0) −7.2 11.1 (4.7) 10.5 (4.7) −0.51 −6.7 <.001
Scaled (−8.3 to −6.2) −1.6 to 0.6) (−8.2 to −5.2)
Secondary outcomes
Secondary
polysomnography
OSA severity
and sleep qualitye
Apnea-hypopnea 0 (0) 13 (26) 13 (26) 0 4 (8) 4 (8) 18% (4 to 32) .01f
index <10, n (%)
Apnea index 12.7 (14.5) 3.1 (5.6) −13.4 13.2 (21.1) 6.8 (12.1) −6.0 −7.4 .04g
(−20.5 to −6.3) (−9.6 to −2.4) (−14.3 to −0.5)
Apnea index, 8.3 0.4 3.6 2.75
median (IQR) (1.5 to 21.0) (0.0 to 4.4) (1.0 to 17.2) (0.7 to 6.25)
3% oxygen 29.0 (17.9) 11.4 (12.7) −17.7 27.0 (19.8) 21.6 (17.8) −4.2 −13.5 .001
desaturation index (−22.2 to −13.3) (−8.9 to 0.4) (−20.0 to −7.1)
(desaturation
events/h
of sleep)
3% oxygen 25.1 6.7 22.1 15.7
desaturation index (15.3 to 43.7) (4.8 to 14.4) (11.0 to 40.6) (9.3 to 34.2)
(desaturation
events/h
of sleep),
median (IQR)
4% oxygen 23.2 (17.8) 8.1 (11.1) −15.3 21.5 (19.9) 15.9 (16.2) −4.3 −11.0 .003
desaturation index (−19.6 to −11.0) (−8.8 to 0.1) (−17.2 to −4.7)
(desaturation
events/h
of sleep)
4% oxygen 17.8 3.6 12.6 9.5
desaturation index (7.6 to 33.6) (2.0 to 8.2) (7.2 to 36.0) (4.1 to 23.6)
(desaturation
events/h
of sleep),
median (IQR)
Lowest oxygen 79.0 (8.7) 83.9 (6.1) 4.9 (2.8 to 7.0) 80.7 (9.1) 81.5 (8.9) 0.4 4.5 <.001
saturation, % (−1.7 to 2.6) (1.5 to 7.5)
Total sleep 8.8 (10.9) 3.8 (8.1) −8.5 8.3 (13.5) 6.0 (12.2) −0.8 −7.7 .008g
time spent (−14.1 to −2.8) (−2.3 to 0.7) (−13.3 to −2.0)
with oxygen
desaturation
<90%, %
Total sleep 4.3 0.7 2.3 1.2
time spent (0.6 to 11.8) (0.1 to 2.1) (0.2 to 8.7) (0.1 to 4.1)
with oxygen
desaturation <90%
median (IQR), %
Arousal index 33.4 (18.6) 19.0 (10.8) −15.1 31.7 (18.1) 25.8 (15.0) −3.9 −11.2 <.001g
(arousals/h (−18.0 to −12.2) (−6.2 to −1.5) (−14.9 to −7.5)
of sleep)
Sleep stages χ 23 = 13.46;
(% total sleep time) P = .004h
N1 11.4 11.8 −0.4 12.1 9.4 −2.7 −3.9 <.001i
(−1.3 to −2.1) (–−7.2 to 1.8) (−5.5 to −2.3)
N2 63.0 56.1 −6.9 61.3 57.7 −3.6 0.1 .87i
(−13.9 to −1.3) (−8.8 to 1.6) (−0.8 to 0.9)
N3 10.7 14.0 3.3 11.7 14.4 2.7 2.6 .75i
(−1.7 to 8.3) (−1.8 to 7.2) (−1.3 to 1.8)
REM 14.9 18.1 3.2 14.9 18.5 3.6 0.8 .38i
(−1.7 to 8.1) (−1.6 to 8.8) (−1.0 to 2.5)
(continued)

Table 2. Estimated Treatment Effects in the Primary and Secondary Outcomes in a Study of the Effect of Upper Airway Surgery vs Ongoing Medical
Management on Patients With Obstructive Sleep Apnea (continued)
Baseline-adjusted
difference
of surgery
Surgery group (n = 50) Medical management group (n = 49) vs medical
Change from Change from management
Baseline, 6 mo, baseline, Baseline, baseline, group,
Outcome mean (SD) mean (SD) mean (95% CI) mean (SD) 6 mo, mean (SD) mean (95% CI) mean (95% CI)a P valueb
Objective daytime
sleepiness
Mean sleep 10.5 (5.2) 11.1 (4.3) 0.8 (−0.5 to 2.1) 11.6 (5.3) 11.9 (4.7) 0.2 0.6 .54k
latency (−1.1 to 1.6) (−1.3 to 2.5)
(min)j
Partner- and
patient-reported
outcomes
Snoring severity 7.7 (0.9) 2.6 (2.3) −5.1 7.1 (1.5) 6.6 (1.7) −0.56 −4.0 <.001
scalel (n = 35) (n = 23) (−5.8 to −4.4) (n = 32) (n = 26) (−1.23 to 0.10) (−4.9 to −3.1)
Functional 15.1 18.6 (1.8) 3.6 (2.9 to 4.2) 16.1 (2.7) 16.3 (2.4) 0.1 (– 0.6 to 0.8) 3.4 (2.5 to 4.4) <.001m
outcomes (2.8)
of Sleep
questionnairen
EQ-5D-5Lo 0.86 (0.20) 0.93 (0.12) 0.06 0.86 (0.10) 0.86 (0.10) 0.00 0.06 .054
(0.02 to 0.11) (−0.03 to 0.04) (−0.00 to 0.12)
EQ visual analog 76.4 (16.4) 85.0 (12.1) 8.8 78.7 (13.2) 76.8 (14.0) −1.7 10.5 <.001
scalep (5.4 to 12.2) (−5.3 to 1.8) (5.6 to 15.4)
Blood pressureq
24 h ambulatory 121.9 (8.4) 120.0 (12.0) −1.5 125.4 (12.2) 124.7 (13.6) −1.3 −0.2 .94
systolic blood (−5.0 to 1.9) (−4.6 to 1.9) (−4.9 to 4.6)
pressure
24 h ambulatory 75.3 (6.0) 74.1 (8.0) −1.3 77.4 (9.1) 77.7 (10.9) −0.4 −0.9 .59
diastolic blood (−3.5 to 1.0) (−2.6 to 1.7) (−4.0 to 2.3)
pressure
Anthropometry
Body mass index 30.7 (3.9) 30.6 (4.2) −0.14 29.5 (3.7) 29.4 (3.7) 0.29 0.43 .11
(−0.51 to 0.23) (−0.10 to 0.68) (−0.10 to 0.97)
Abbreviations: EQ, EuroQol; EQ-5D-5L, EuroQol 5-dimension 5-level daytime nap opportunities when the patient is instructed to try to fall asleep.
questionnaire; N, nonrapid eye movement stage; OSA, obstructive sleep apnea; Values below 10 minutes signify an increased propensity to fall asleep.
REM, rapid eye movement sleep. The minimum important clinical difference is 1 minute2.
a k
Using the group × visit interaction term from a linear mixed-effects model with Measured by the Multiple Sleep Latency Test, mean sleep latency calculated as
group, visit (baseline or 6 months), and group × visit as fixed effects and the mean time to sleep onset after lights out on 5 daytime 20-minute sleep
participant as random intercept. opportunities spaced 2 hours apart.
b l
For group × visit interaction term. Snoring severity scale22 evaluates snoring (range, 0-9; higher scores indicate
c
For definition see footnotes for Table 1. more intense snoring).
m
d
For definition see footnotes for Table 1. Assessed using a linear mixed effects model with bias corrected and
e
accelerated bootstrapped 95% CIs.
Available age-appropriate normal values for secondary polysomnographic
n
parameters: lowest oxygen saturation, 90.5% (95% CI, 89.3%-91.7%); arousal Functional Outcomes of Sleep Questionnaire23 is a measure for sleep-specific
index, 12.5 (95% CI, 10.7-14.2); N1 sleep, 8.0% of sleep time (95% CI, quality of life (range, 5-20; higher scores indicate better functional status;
6.9%-9.2%); N2 sleep, 52.2% of sleep time (95% CI, 50.6%-53.8%); N3 sleep, normal is considered a score of ⱖ17.9; a score change of 1 is considered to be
20.4% of sleep time (95% CI, 18.5%-22.2%); REM sleep, 19.3% of sleep time the minimal clinically important difference24).
(95% CI, 18.2%-20.3%).21 There are no agreed minimum important clinical o
EuroQol group EQ-5D-5L26 questionnaire is a measure of general
difference values for secondary polysomnography parameters. health-related quality of life (utility index range, −0.594 to 125; higher index
f
Assessed using Fisher exact test. score indicates better quality of life; score changes ranging from 0.03-0.52
g
are considered to be the minimally important differences in other diseases
Assessed using mixed-effects model with a Poisson distribution to account for
[there is no minimal clinically important difference established for OSA]27).
data nonnormality, the mean differences were estimated from these models.
p
h EQoL-5D-5L visual analogue scale26 is a measure of self-rated general health
Using χ2 test of association for overall difference between groups across the
status (range, 0 [worst possible health] to 100 [best possible health]; score
4 stages of sleep at 6 months.
changes ranging from 3.5-10.1 are considered to be the minimal clinically
i
Using a mixed-effects logistic regression model for each separate sleep stage important differences in other diseases).28,29
with adjustment for baseline percentages. q
The minimal clinically important difference for 24-hour ambulatory blood
j
Mean sleep latency is the average time to fall asleep (measured by pressure is 1 mm Hg.2
polysomnography in a sleep laboratory) across 5 equally spaced 20-minute
Adverse Events anticoagulation therapy on postoperative day 14, and recur-

There were 6 serious adverse events in 4 participants in the rent angina requiring a second coronary artery stent on post-
surgery group and no serious adverse events in the ongoing operative day 21. Another serious adverse event in a different
medical management group. Three serious adverse events patient was hospital readmission lasting more than 24 hours
occurred in the same patient: myocardial infarction on post- for observation (a criterion for serious adverse event)
operative day 5, tonsillar fossa bleeding after initiation of after hematemesis of old blood on postoperative day 10.

associated with significant functional impairment (Table 3;

Table 3. Adverse Events in a Study of the Effect of Upper Airway Surgery
vs Ongoing Medical Management on Patients With Moderate or Severe see eTable 9 in Supplement 2 for further details of all serious
Obstructive Sleep Apnea and nonserious adverse events).
No. of events
Medical
Surgery management
Adverse event group group Discussion
Seriousa and related to surgical procedure
In this randomized clinical trial, multilevel upper airway sur-
Results in death 0
gery, compared with ongoing medical management, resulted
Life-threatening 1
in significant reductions in the frequency of sleep apneas and
Requires in-patient hospitalization 2
(>24 h) or prolongation of existing
hypopneas and daytime sleepiness in patients with moder-
hospitalization ate or severe OSA in whom prior attempts at conventional medi-
Results in persistent or significant disability 0 cal device treatment had failed. Surgery was also associated
or incapacity
with improvements in most other polysomnography mea-
Seriousa and unrelated to surgical procedure
sures (arterial oxygen saturation measures and cortical arousal
Results in death 0 0
frequency), partner-reported snoring, and patient-reported
Life-threatening 0 0
sleep-specific quality of life and general health status. Mean
Requires in-patient hospitalization 3 0
(>24 h) or prolongation of existing sleep latency and blood pressure values were in the normal
hospitalization range and were unchanged at 6 months.
Results in persistent or significant disability 0 0 The statistically significant between-group difference in
or incapacity
Nonserious and related to surgical procedure
the AHI was above the established minimal clinically impor-
tant difference (15 events/h) 2 but less than the a priori
Minor postoperative tonsil bleeds 5
(Stammberger grade A-B; hospitalization hypothesized difference of 20 events per hour.12 The accom-
for observation)
panying significant decrease in ESS exceeded the a priori suf-
Hospital admission <24 h 1
(for observation only) ficiently important difference of 3 for the trial.12 The signifi-
Globus pharyngeusb (at 6 mo) 0 cant improvements in self-reported sleepiness and sleep-
Taste changes (at 6 mo) 1 specific quality of life were considerably greater than those
Tongue numbness (at 6 mo) 0 found in patients with OSA treated with CPAP.2 Although the
Tongue weakness (at 6 mo) 0 lack of change in the multiple sleep latency test might appear
VPI speech (at 6 mo) 0 discordant with the marked change in ESS, these 2 tests mea-
VPI swallowing/regurgitation (at 6 mo) 1 sure different aspects of daytime sleepiness as demonstrated
VPI hypernasality (at 6 mo) 0
by their poor correlation in OSA populations.32 Compared
Other (excess saliva, feeling of scar tissue 2
with ESS, mean sleep latency is relatively insensitive to
on roof of mouth) change with OSA treatment2 and, unlike ESS, was within nor-
Nonserious and unrelated to surgical procedure mal limits at baseline.
Planned elective or hospital admission 2 3 The significant surgery-related improvements in this study
(<24 h)
are similar to those reported in 2 previous surgery random-
Injuries or other medical conditions 6 5
ized clinical trials8,9 conducted in patients with similar OSA
Abbreviation: VPI, velopharyngeal insufficiency. severity. However, these trials used uvulopalatopharyngo-
a
There were 6 serious adverse events in 4 participants in the surgery group and plasty alone in patients because of predominant retropalatal
0 serious adverse events in the ongoing medical management group. Three
obstruction and/or palatine tonsil enlargement (ie, Friedman
serious adverse events occurred in the same patient. Two other patients
had a serious adverse event prior to surgery. Further clinical details concerning stage I or II). Most patients with OSA have multilevel obstruc-
all adverse events are located in eTable 10 in Supplement 2. tion, including increased tongue size due to fat deposition.33
b
Globus pharyngeus is a persistent or intermittent nonpainful sensation of a Thus, this trial of multilevel surgery supports a broader role
lump or foreign body in the throat. for upper airway surgery to manage OSA and expands on an
earlier randomized clinical trial of multilevel minimally inva-
The patient was hemodynamically stable with a normal sive surgery in patients with mild disease.10 The more exten-
hemoglobin concentration and was admitted to the hospital sive approach used in the present study had a greater treat-
for observation. The remaining 2 serious adverse events (hos- ment effect, whereas the serious adverse event risk was
pital admission for asthma/bronchitis and colitis) occurred in similar to a large observational cohort of predominantly uvu-
2 participants after randomization but before the surgery. lopalatopharyngoplasy alone. 34 None of the participants
Thus, 2 of the 50 participants (4%) who underwent the sur- reported significant long-term functional difficulties. Two
gery were considered to have serious adverse events possibly participants experienced serious adverse events potentially
related to surgery and 0 of the 49 participants in the ongoing related to surgery (another 2 participants randomized to the
medical management group experienced a serious adverse surgery group had serious adverse events before undergoing
event (between-group difference, 4.0% [95% CI, –3.8% to the surgical procedures).
13.5%]). At 6 months, 4 participants in the surgery group Based on the preliminary study cohort, 14 and that
reported oral or pharyngeal symptoms, none of which were nonanatomical as well as anatomical factors contribute to

OSA,4 it was anticipated that this surgical intervention would Limitations

reduce, not eliminate, obstructive breathing events. The This study has several limitations. First, although the study was
reduction in AHI in the surgery group was substantial and adequately powered to establish efficacy, generalizability from
similar to the net effect of CPAP treatment35 and the decrease any randomized clinical trial is inherently limited by numbers
in AHI achieved with oral appliances36 and hypoglossal nerve of patients and surgeons, and this study did not meet the suf-
stimulation.37 Most importantly, this study has shown sub- ficiently important difference for AHI (but did surpass the mini-
stantial improvements in patient-centered outcomes in mal clinically important difference). Thus, further studies will
patients unable to use conventional OSA treatment. The sur- be needed to establish the long-term effectiveness, safety, and
gery does not preclude reintroducing CPAP or other therapies cost-effectiveness of this surgical treatment for OSA. Second,
later, if required. The perception that CPAP treatment is prob- this study included a select population that excluded patients
lematic after uvulopalatopharyngoplasty arises from a single with severe obesity (ie, body mass index of 38 or greater), pa-
early report of more mouth leaks with nasal CPAP after exci- tients older than 70 years, and patients with retrognathia and
sional uvulopalatopharyngoplasty.38 However, the modified significant comorbidities; women were underrepresented in the
uvulopalatopharyngoplasty used in this study reduces retro- trial. Therefore, the results may not generalize to the larger OSA
palatal obstruction while preserving the palate and velopha- population. Third, because the surgical intervention caused pain
ryngeal sphincter function such that problems with reappli- and anatomical changes, it was not possible to blind patients
cation of CPAP are rare.39 and some of the clinical assessors to treatment group random-
The strengths of this study include the randomized clini- ization. Hence, some of the observed effects, such as self-
cal trial design, sufficient sample size and duration of fol- reported sleepiness, may have been influenced by participant
low-up to ascertain treatment effects independent of short- expectancy, although this bias is less likely to have affected the
term postoperative discomfort and physiological disturbance, blinded objective measures of OSA (polysomnography).
systematic recording of adverse events, and low rates of par-
ticipant withdrawal and loss to follow-up. Standardization of
the surgical intervention was done to try to ensure consis-
tency among the trial surgeons at multiple sites. The surgical
Conclusions
technique is similar to other contemporary, widely used uvu- In this preliminary study of adults with moderate or severe OSA
lopalatopharyngoplasties that open the lateral palate,8,9 and who had failed conventional treatment, combined palatal and
radiofrequency is a common otolaryngologic intervention. The tongue surgery, compared with ongoing medical management,
findings may have broader clinical relevance because the sur- reduced the number of apnea and hypopnea events and patient-
gical exclusion criteria were relatively limited and most ana- reported sleepiness at 6 months. Further research is needed to
tomical subtypes were included, as 84% of patients meeting confirm these findings in additional populations and to under-
general screening and medical criteria were surgically eli- stand clinical utility, long-term efficacy, and safety of multi-
gible and enrolled in the trial. level upper airway surgery for treatment of patients with OSA.
ARTICLE INFORMATION (Jones); Health Economics Unit, College of responsibility for the integrity of the data and the
Accepted for Publication: July 15, 2020. Medicine and Public Health, Flinders University, accuracy of the data analysis.
Adelaide, SA, Australia (Kaambwa); Hollywood Concept and design: MacKay, Carney, Catcheside,
Published Online: September 4, 2020. Medical Centre, Perth, WA, Australia (Lewis); Chai-Coetzer, Chia, Cistulli, Hodge, Weaver, Woods,
doi:10.1001/jama.2020.14265 Department of Otolaryngology, Head & Neck Yeo, McEvoy.
Author Affiliations: Illawarra Shoalhaven Local Surgery, Royal Perth Hospital, Perth, WA, Australia Acquisition, analysis, or interpretation of data: All
Health District, Wollongong, NSW, Australia (Lewis); Department of Otolaryngology, Head and authors.
(MacKay, Jones); University of Wollongong, NSW, Neck Surgery, Flinders Medical Centre, Adelaide, Drafting of the manuscript: MacKay, Carney,
Australia (MacKay, Jones); Illawarra ENT Head and SA, Australia (Ooi, Woods); West Australian Sleep Catcheside, Chia, Cistulli, Hodge, Jones, Woodman,
Neck Clinic, Wollongong, NSW, Australia (MacKay); Disorders Research Institute, Queen Elizabeth II Woods, Yeo, McEvoy.
Southern ENT & Adelaide Sinus Centre, Flinders Medical Centre, Perth, WA, Australia (McArdle, Critical revision of the manuscript for important
Private Hospital, Adelaide, SA, Australia (Carney); Singh); Department of Pulmonary Physiology and intellectual content: MacKay, Catcheside,
College of Medicine and Public Health, Flinders Sleep Medicine, Sir Charles Gairdner Hospital, Chai-Coetzer, Chia, Cistulli, Hodge, Jones,
University, Adelaide, SA, Australia (Carney, Ooi, Perth, WA, Australia (McArdle, Singh); The Kaambwa, Lewis, Ooi, Pinczel, McArdle, Rees,
Woods); Adelaide Institute for Sleep Health, College Memorial Hospital, Adelaide, SA, Australia (Rees); Singh, Stow, Weaver, Woodman, Woods, Yeo,
of Medicine and Public Health, Flinders University, Faculty of Human Sciences, University of Western McEvoy.
Adelaide, SA, Australia (Catcheside, Chai-Coetzer, Australia, Perth, WA, Australia (Singh); The Statistical analysis: Catcheside, Kaambwa, Weaver,
Pinczel, McEvoy); Respiratory and Sleep Service, Woolcock Clinic, University of Sydney, NSW, Woodman, Woods, Yeo.
Southern Adelaide Local Health Network, Adelaide, Australia (Stow); Department of Otolaryngology/ Obtained funding: MacKay, Carney, Catcheside,
SA, Australia (Chai-Coetzer, McEvoy); Department Head and Neck Surgery, University of Washington, Chai-Coetzer, Cistulli, Ooi, Weaver, Woods, McEvoy.
of Thoracic Medicine, Royal Adelaide Hospital, Seattle (Weaver); Staff Surgeon, Seattle Veterans Administrative, technical, or material support:
Adelaide, SA, Australia (Chia, Yeo); Charles Perkins Affairs Medical Center, Seattle, Washington MacKay, Carney, Catcheside, Chai-Coetzer, Chia,
Centre, Faculty for Medicine and Health, University (Weaver); Flinders Centre for Epidemiology and Jones, Ooi, Pinczel, McArdle, Rees, Stow, Woods.
of Sydney, NSW, Australia (Cistulli); Department of Biostatistics, College of Medicine and Public Health, Supervision: MacKay, Chai-Coetzer, Chia, Cistulli,
Respiratory and Sleep Medicine, Royal North Shore Flinders University, Adelaide, SA, Australia Hodge, Jones, Ooi, Rees, McEvoy.
Hospital, Sydney, NSW, Australia (Cistulli); Ear Nose (Woodman). Other - Trial PI: McEvoy.
and Throat Department, Royal Adelaide Hospital, Author Contributions: Drs McEvoy and Woodman Conflict of Interest Disclosures: Dr MacKay
Adelaide, SA, Australia (Hodge); Illawarra Sleep had full access to all the data in the study and take reported receiving grants from National Health and
Medicine Centre, Wollongong, NSW, Australia Medical Research Council of Australia, Flinders

University, and The Repat Foundation 2013 Prabha Australia, Flinders University, and The Repat Antic, PhD (Flinders University). Dr Antic brought
Seshadri Research Grant during the conduct of the Foundation during the conduct of the study and together the collaboration of sleep physicians and
study and nonfinancial support from Genio-Nyxoah grants from Philips Respironics and ResMed outside surgeons, led the funding proposal, and was the
and grants from Garnett-Passe Rodney Williams the submitted work. No other disclosures were study’s principal investigator before his untimely
Foundation and Illawarra Health and Medical reported. death (in 2016). We thank the patients who
Research Institute outside the submitted work. Funding/Support: This study is supported by a participated in this trial; the various clinical and
Dr Carney reported receiving grants from National project grant from the National Health and Medical research teams of the Sleep and Respiratory, and
Health and Medical Research Council of Australia, Research Council of Australia (1059510). Otolaryngology Head and Neck Surgery
Flinders University, and The Repat Foundation Supplementary trial funding was provided by departments; and the technicians in the core sleep
Prabha Seshadri Research Grant during the conduct Flinders University and The Repat Foundation laboratory at the Adelaide Institute of Sleep Health
of the study. Dr Catcheside reported receiving Prabha Seshadri Research Grant. Dr McEvoy was for their work on the study.
grants from National Health and Medical Research supported by a practitioner fellowship of the
Council of Australia and from Flinders University National Health and Medical Research Council (GNT REFERENCES
during the conduct of the study; receiving grants 1079785). Dr Catcheside was supported by an 1. Xie C, Zhu R, Tian Y, Wang K. Association of
from the Cooperative Research Centre for Australian Research Council Future Fellowship obstructive sleep apnoea with the risk of vascular
Alertness, Safety and Productivity, the National (FT120100510). Dr. Weaver’s effort was supported outcomes and all-cause mortality: a meta-analysis.
Health and Medical Research Council of Australia, by the Unites States National Institutes of Health BMJ Open.2017;7(12):e013983. doi:10.1136/
and the Flinders Foundation Health Seed Grant and (R01 HL084139, PI Weaver) and the Veterans bmjopen-2016-013983
nonfinancial support from Philips Respironics, Air Affairs Puget Sound Health Care System.
Liquide Healthcare, and Gorman Promed outside 2. Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel
the submitted work; having a patent to Sleep Role of the Funder/Sponsor: The sponsors had no SR, Harrod CG. Treatment of adult obstructive sleep
Disorder Diagnosis, App No. AU 2018904007, US role in the design and conduct of the study; apnea with positive airway pressure: an american
62/812066 pending and a patent to decision collection, management, analysis, and academy of sleep medicine systematic review,
support software for sleep disorder identification, interpretation of the data; preparation, review, or meta-analysis, and GRADE assessment. J Clin Sleep
February 28, 2019, US 61/815562 Sleep Disorder approval of the manuscript; and decision to submit Med. 2019;15(2):301-334. doi:10.5664/jcsm.7638
Data Fidelity Management System, March 8, 2019, the manuscript for publication. The contents of this 3. Tregear S, Reston J, Schoelles K, Phillips B.
pending. Dr Chai-Coetzer reported receiving grants article do not represent the views of the US Obstructive sleep apnea and risk of motor vehicle
from the National Health and Medical Research government. crash: systematic review and meta-analysis. J Clin
Council of Australia, Flinders University, and The Group Information: The Sleep Apnea Multilevel Sleep Med. 2009;5(6):573-581. doi:10.5664/jcsm.
Repat Foundation during the conduct of the study. Surgery (SAMS) Trial Group Investigators: Stuart 27662
Dr Cistulli reported receiving grants from the MacKay, MD; A. Simon Carney, DM; Peter G. 4. Eckert DJ, White DP, Jordan AS, Malhotra A,
National Health and Medical Research Council of Catcheside, PhD; Ching Li Chai-Coetzer, MD, PhD; Wellman A. Defining phenotypic causes of
Australia, Flinders University, and The Repat Michael Chia, MD; Peter A. Cistulli, MD, PhD; obstructive sleep apnea. Identification of novel
Foundation Prabha Seshadri Research Grant during John-Charles Hodge, MD; Andrew Jones, MD; therapeutic targets. Am J Respir Crit Care Med.
the conduct of the study and nonfinancial support Billingsley Kaambwa, PhD; Richard Lewis, MD; Eng 2013;188(8):996-1004. doi:10.1164/rccm.201303-
from ResMed Inc; nonfinancial support from Zephyr H. Ooi, MD, PhD; Alison Pinczel, PhD; Nigel 0448OC
Sleep Technologies; personal fees from SomnoMed, McArdle, MD; Guy Rees, MD; Bhajan Singh, MD,
Signifier Medical, Wolter Kluwers, and PhD; Nicholas Stow, MD; Edward M. Weaver, MD, 5. Weaver TE, Grunstein RR. Adherence to
Quintessence Publishing; and a provision of clinical MPH; Richard J. Woodman, PhD; Charmaine M. continuous positive airway pressure therapy: the
trial services from Bayer outside the submitted Woods, PhD; Aeneas Yeo, MD; Nick A. Antic, PhD; challenge to effective treatment. Proc Am Thorac Soc.
work. Dr Jones reported receiving grants from R. Doug McEvoy, MD. Data and safety monitoring 2008;5(2):173-178. doi:10.1513/pats.200708-119MG
Illawarra Sleep Medicine Centre during the conduct board: Matthew Naughton, MD (sleep and 6. Sutherland K, Vanderveken OM, Tsuda H, et al.
of the study. Dr Kaambwa reported receiving grants respiratory medicine specialist; Alfred Hospital and Oral appliance treatment for obstructive sleep
from the Australian National Health and Medical Monash University, Melbourne, Australia); apnea: an update. J Clin Sleep Med. 2014;10(2):215-
Research Council during the conduct of the study. Nathaniel Marshall, PhD (clinical trialist, 227. doi:10.5664/jcsm.3460
Dr Lewis reported receiving consulting fees for epidemiologist, sleep disorders specialist; 7. Caples SM, Rowley JA, Prinsell JR, et al. Surgical
Nyxoah SA (Belgium) as an investigator in 3 trials of University of Sydney and The Woolcock Medical modifications of the upper airway for obstructive
a new hypoglossal nerve stimulator for obstructive Institute, Sydney, Australia); and William Coman, sleep apnea in adults: a systematic review and
sleep apnea. Dr Ooi reported receiving grants from AM, MD (consultant ENT surgeon; University of meta-analysis. Sleep. 2010;33(10):1396-1407. doi:
the National Health and Medical Research Council Queensland). Sleep laboratory managers: Jeremy 10.1093/sleep/33.10.1396
and Flinders University during the conduct of the Mercer, PhD (Flinders Medical Centre); Terry Sands,
study and personal fees from Medtronic outside the MD (Wollongong Hospital); Pam Singh, BSc(Hons) 8. Browaldh N, Nerfeldt P, Lysdahl M, Bring J,
submitted work. Dr Pinczel reported receiving (Royal Adelaide Hospital); Neill Madeira, BHealthSc Friberg D. SKUP3 randomised controlled trial:
grants from the National Health and Medical (Sir Charles Gairdner Hospital); Gary Cohen, PhD polysomnographic results after uvulopalatopharyn-
Research Council of Australia, Flinders University, (for Sydney site). Corelab manager: Jeremy Mercer, goplasty in selected patients with obstructive sleep
and The Repat Foundation during the conduct of PhD. Corelab scoring: Laura Bandick, BPsych(Hons); apnoea. Thorax. 2013;68(9):846-853. doi:10.1136/
the study. Dr McArdle reported receiving grants Michaela O’Keefe, BPsych(Hons). Additional site thoraxjnl-2012-202610
from the National Health and Medical Research coordinators: Alison Teare, BSc, BEd; Kelsey 9. Sommer UJ, Heiser C, Gahleitner C, et al.
Council of Australia, Flinders University, and The Johnson, BPsych(Hons); Natasha Umrigar, Tonsillectomy with uvulopalatopharyngoplasty in
Repat Foundation Prabha Seshadri Research Grant BmedHlthSciAdv(Hons); Sue-Ellen Holmes, BSc obstructive sleep apnea. Dtsch Arztebl Int. 2016;113
during the conduct of the study and grants from (Hons); Kate Sutherland, PhD; Aimee Lowth, BSc (1-02):1-8. doi:10.3238/arztebl.2016.0001
Oventus (Brisbane, Australia), Nyxoah (Mont-Saint (Hons); Clare Rea, BSc, BA. 10. Woodson BT, Steward DL, Weaver EM,
Guibert, Belgium), and Zelda Therapeutics Meeting Presentation: This study was presented Javaheri S. A randomized trial of temperature-
(Australia) outside the submitted work. Dr Weaver at the Australasian Sleep Association Conference; controlled radiofrequency, continuous positive
reported being a research consultant for Nyxoah SA October 19, 2018; Brisbane, Australia, and at the airway pressure, and placebo for obstructive sleep
outside the submitted work and practicing sleep virtual European Respiratory Society International apnea syndrome. Otolaryngol Head Neck Surg.
surgery. Dr Yeo reported receiving grants from the Congress; September 7, 2020. 2003;128(6):848-861. doi:10.1016/S0194-5998(03)
National Health and Medical Research Council of 00461-3
Australia, Flinders University, Flinders University, Data Sharing Statement: See Supplement 3.
and The Repat Foundation Prabha Seshadri Additional Contributions: This work would not 11. Vicini C, Meccariello G, Montevecchi F, et al.
Research Grant during the conduct of the study. have been possible without both the late Samuel Effectiveness of barbed repositioning
Dr McEvoy reported receiving grants from the Robinson, MD (Flinders Medical Centre), who pharyngoplasty for the treatment of obstructive
National Health and Medical Research Council of pioneered the surgical technique and the late Nick sleep apnea (OSA): a prospective randomized trial.

Sleep Breath. 2020;24(2):687-694. doi:10.1007/ 21. Boulos MI, Jairam T, Kendzerska T, Im J, framework of clinical significance. Med Decis Making.
s11325-019-01956-7 Mekhael A, Murray BJ. Normal polysomnography 2005;25(3):250-261. doi:10.1177/
12. Carney AS, Antic NA, Catcheside PG, et al. Sleep parameters in healthy adults: a systematic review 0272989X05276863
Apnea Multilevel Surgery (SAMS) trial protocol: and meta-analysis. Lancet Respir Med. 2019;7(6): 32. Li Y, Zhang J, Lei F, Liu H, Li Z, Tang X.
a multicenter randomized clinical trial of upper 533-543. doi:10.1016/S2213-2600(19)30057-8 Self-evaluated and close relative-evaluated
airway surgery for patients with obstructive sleep 22. Lim PV, Curry AR. A new method for evaluating Epworth Sleepiness Scale vs. multiple sleep latency
apnea who have failed continuous positive airway and reporting the severity of snoring. J Laryngol Otol. test in patients with obstructive sleep apnea. J Clin
pressure. Sleep. 2019;42(6):1-8. doi:10.1093/sleep/ 1999;113(4):336-340. doi:10.1017/ Sleep Med. 2014;10(2):171-176. doi:10.5664/jcsm.
zsz056 S0022215100143919 3446
13. Saghaei M, Saghaei S. Implementation of an 23. Weaver TE, Laizner AM, Evans LK, et al. 33. Kim AM, Keenan BT, Jackson N, et al. Tongue
open-source customizable minimization program An instrument to measure functional status fat and its relationship to obstructive sleep apnea.
for allocation of patients to parallel groups in clinical outcomes for disorders of excessive sleepiness. Sleep. Sleep. 2014;37(10):1639-1648. doi:10.5665/sleep.
trials. J Biomedical Science and Engineering 2011;4 1997;20(10):835-843. 4072
(11):6. doi:10.4236/jbise.2011.411090 24. Billings ME, Rosen CL, Auckley D, et al. 34. Kezirian EJ, Weaver EM, Yueh B, et al.
14. MacKay SG, Carney AS, Woods C, et al. Psychometric performance and responsiveness of Incidence of serious complications after
Modified uvulopalatopharyngoplasty and coblation the functional outcomes of sleep questionnaire and uvulopalatopharyngoplasty. Laryngoscope. 2004;
channeling of the tongue for obstructive sleep sleep apnea quality of life instrument in a 114(3):450-453. doi:10.1097/00005537-
apnea: a multi-centre Australian trial. J Clin Sleep Med. randomized trial: the HomePAP study. Sleep. 2014; 200403000-00012
2013;9(2):117-124. doi:10.5664/jcsm.2402 37(12):2017-2024. doi:10.5665/sleep.4262 35. Ravesloot MJL, de Vries N. Reliable calculation
15. Friedman M, Ibrahim H, Joseph NJ. Staging of 25. van Hout B, Janssen MF, Feng YS, et al. Interim of the efficacy of non-surgical and surgical
obstructive sleep apnea/hypopnea syndrome: scoring for the EQ-5D-5L: mapping the EQ-5D-5L to treatment of obstructive sleep apnea revisited. Sleep.
a guide to appropriate treatment. Laryngoscope. EQ-5D-3L value sets. Value Health. 2012;15(5):708- 2011;34(1):105-110. doi:10.1093/sleep/34.1.105
2004;114(3):454-459. doi:10.1097/00005537- 715. doi:10.1016/j.jval.2012.02.008 36. Zhu Y, Long H, Jian F, et al. The effectiveness of
200403000-00013 26. EQ-5D-5L User Guide. EuroQol Research oral appliances for obstructive sleep apnea
16. Note for Guidance on Clinical Safety Data Foundation;2019. Accessed April 1, 2020. https:// syndrome: a meta-analysis. J Dent. 2015;43(12):
Management: Definitions and Standards for euroqol.org/publications/user-guides 1394-1402. doi:10.1016/j.jdent.2015.10.008
Expedited Reporting (CPMP/ICH/377/95). Therapeutic 27. Coretti S, Ruggeri M, McNamee P. The 37. Strollo PJ Jr, Soose RJ, Maurer JT, et al; STAR
Goods Administration; 2000:13. minimum clinically important difference for EQ-5D Trial Group. Upper-airway stimulation for
17. Iber C, Ancoli-Israel S, Chesson A, Quan SF. index: a critical review. Expert Rev Pharmacoecon obstructive sleep apnea. N Engl J Med. 2014;370(2):
The AASM Manual for the Scoring of Sleep and Outcomes Res. 2014;14(2):221-233. doi:10.1586/ 139-149. doi:10.1056/NEJMoa1308659
Associated Events: Rules, Terminology and Technical 14737167.2014.894462 38. Mortimore IL, Bradley PA, Murray JA,
Specifications. American Academy of Sleep Medicine; 28. Mulhern B, O’Gorman H, Rotherham N, Douglas NJ. Uvulopalatopharyngoplasty may
2007. Brazier J. Comparing the measurement equivalence compromise nasal CPAP therapy in sleep apnea
18. Littner MR, Kushida C, Wise M, et al; Standards of EQ-5D-5L across different modes of syndrome. Am J Respir Crit Care Med. 1996;154(6 Pt
of Practice Committee of the American Academy of administration. Health Qual Life Outcomes. 2015;13: 1):1759-1762. doi:10.1164/ajrccm.154.6.8970367
Sleep Medicine. Practice parameters for clinical use 191. doi:10.1186/s12955-015-0382-6 39. Khan A, Ramar K, Maddirala S, Friedman O,
of the multiple sleep latency test and the 29. Nolan CM, Longworth L, Lord J, et al. The Pallanch JF, Olson EJ. Uvulopalatopharyngoplasty
maintenance of wakefulness test. Sleep. 2005;28 EQ-5D-5L health status questionnaire in COPD: in the management of obstructive sleep apnea: the
(1):113-121. doi:10.1093/sleep/28.1.113 validity, responsiveness and minimum important mayo clinic experience. Mayo Clin Proc. 2009;84
19. Johns MW. A new method for measuring difference. Thorax. 2016;71(6):493-500. doi:10. (9):795-800. doi:10.4065/84.9.795
daytime sleepiness: the Epworth sleepiness scale. 1136/thoraxjnl-2015-207782 40. Schriger DL. Graphic portrayal of studies with
Sleep. 1991;14(6):540-545. doi:10.1093/sleep/14.6. 30. Robinson K, Gatehouse S, Browning GG. paired data: a tutorial. Ann Emerg Med. 2018;71(2):
540 Measuring patient benefit from otorhinolaryngo- 239-246. doi:10.1016/j.annemergmed.2017.05.033
20. Crook S, Sievi NA, Bloch KE, et al. Minimum logical surgery and therapy. Ann Otol Rhinol Laryngol.
important difference of the Epworth Sleepiness 1996;105(6):415-422. doi:10.1177/
Scale in obstructive sleep apnoea: estimation from 000348949610500601
three randomised controlled trials. Thorax. 2019;74 31. Barrett B, Brown D, Mundt M, Brown R.
(4):390-396. Sufficiently important difference: expanding the

The Laryngoscope
© 2021 The American Laryngological,
Rhinological and Otological Society, Inc.
Impact of Body Mass Index and Discomfort on Upper Airway

Stimulation: ADHERE Registry 2020 Update
Maria V. Suurna, MD ; Armin Steffen, MD ; Maurits Boon, MD; Eugene Chio, MD; Marcel Copper, MD;
Reena Dhanda Patil, MD; Katherine Green, MD; Ronald Hanson, MD; Clemens Heiser, MD ;
Colin Huntley, MD ; David Kent, MD; Christopher Larsen, MD; Shalini Manchanda, MD;
Joachim T. Maurer, MD; Ryan Soose, MD; Nico de Vries, MD; Harneet K. Walia, MD; and
Erica Thaler, MD, ADHERE Registry Investigators
Objectives/Hypothesis: To provide the ADHERE registry Upper Airway Stimulation (UAS) outcomes update, including
analyses grouped by body mass index (BMI) and therapy discomfort.
Study Design: Prospective observational study.
Methods: ADHERE captures UAS outcomes including apnea-hypopnea index (AHI), Epworth sleepiness scale (ESS), ther-
apy usage, patient satisfaction, clinician assessment, and safety over a 1-year period. BMI ≤32 kg/m2 (BMI32) and 32 < BMI
≤35 kg/m2 (BMI35) group outcomes were examined.
Results: One thousand eight hundred forty-nine patients enrolled in ADHERE, 1,019 reached final visit, 843 completed
the visit. Significant changes in AHI (20.9, P < .0001) and ESS ( 4.4, P < .0001) were demonstrated. Mean therapy usage
was 5.6 2.2 hr/day. Significant therapy use difference was present in patients with reported discomfort versus no discomfort
(4.9 2.5 vs. 5.7 2.1 hr/day, P = .01). Patients with discomfort had higher final visit mean AHI versus without discomfort
(18.9 18.5 vs. 13.5 13.7 events/hr, P = .01). Changes in AHI and ESS were not significantly different. Serious adverse
events reported in 2.3% of patients. Device revision rate was 1.9%. Surgical success was less likely in BMI35 versus BMI32
patients (59.8% vs. 72.2%, P = .02). There was a significant therapy use difference: 5.8 2.0 hr/day in BMI32 versus
5.2 2.2 hr/day in BMI35 (P = .028).
Conclusions: Data from ADHERE demonstrate high efficacy rates for UAS. Although surgical response rate differs
between BMI32 and BMI35 patient groups, the AHI and ESS reduction is similar. Discomfort affects therapy adherence and effi-
cacy. Thus, proper therapy settings adjustment to ensure comfort is imperative to improve outcomes.
Key Words: Hypoglossal nerve stimulation, upper airway stimulation, sleep apnea, sleep surgery, neurostimulation.
Level of Evidence: 4
Laryngoscope, 131:2616–2624, 2021
INTRODUCTION associated with multiple medical comorbidities, prema-

Moderate-to-severe obstructive sleep apnea (OSA) ture death, motor vehicle accidents, poor quality of life,
is a prevalent disorder and when left untreated is and decreased work productivity.1 Positive airway
From the Department of Otolaryngology-Head and Neck Surgery (M.V.S.), Weill Cornell Medicine/New York Presbyterian Hospital, New York,
New York, U.S.A.; Department of Otorhinolaryngology (A.S.), University of Lübeck, Lübeck, Germany; Department of Otolaryngology - Head and Neck
Surgery (M.B., C.H.), Thomas Jefferson University Hospital; Department of Otolaryngology – Head and Neck Surgery (E.C.), Ohio State University,
Columbus, Ohio, U.S.A.; Department of Otolaryngology-Head and Neck Surgery (M.C.), St. Antonius Hospital, Nieuwegein, The Netherlands; Department of
Otolaryngology – Head and Neck Surgery (R.D.P.), University of Cincinnati College of Medicine, Cincinnati, Ohio, U.S.A.; Department of Surgical Services
(R.D.P.), Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, U.S.A.; Department of Otolaryngology (K.G.), University of Colorado, Denver,
Colorado, U.S.A.; Otolaryngology, St. Cloud Ear, Nose, Throat Clinic (R.H.), St. Cloud, Minnesota, U.S.A.; Department of Otorhinolaryngology, Head and
Neck Surgery (C.H.), Technische Universität München, Munich, Germany; Department of Otolaryngology (D.K.), Vanderbilt University Medical Center,
Nashville, Tennessee, U.S.A.; Department of Otolaryngology-Head and Neck Surgery (C.L.), Kansas University Medical Center, Andover, Kansas, U.S.A.;
Section of Pulmonary, Critical Care, Sleep and Occupational Medicine (S.M.), Indiana University School of Medicine and Indiana University Health,
Indianapolis, Indiana, U.S.A.; Division of Sleep Medicine, Department of Otorhinolaryngology, Head and Neck Surgery (J.T.M.), University Medical Center
Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Division of Sleep Surgery, Department of Otolaryngology, Pittsburgh
School of Medicine, UPMC Mercy (R.S.), University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.; Department of Ear, Nose and Throat, OLVG,
Department of Oral Kinesiology (N.D.V.), ACTA Amsterdam, Amsterdam, The Netherlands; Cleveland Clinic, Sleep Disorders Center (H.K.W.),
Neurological Institute, Cleveland, Ohio, U.S.A.; and the Center for Sleep and Circadian Neurobiology (E.T.), University of Pennsylvania, Philadelphia,
Pennsylvania, U.S.A.
The study is financially supported by Inspire Medical Systems.
Editor’s Note: This Manuscript was accepted for publication on July 6, 2021.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Abstract was accepted for podium presentation at the Combined Otolaryngology Spring Meeting (COSM) April 22–26, 2020 in Atlanta, Georgia.
Cancelled due to COVID-19 pandemic.
Send correspondence to Maria V. Suurna, MD, Department of Otolaryngology-Head and Neck Surgery, Weill Cornell Medicine/New York
Presbyterian Hospital, New York, NY. E-mail: [email protected]
DOI: 10.1002/lary.29755
Laryngoscope 131: November 2021 Suurna et al.: ADHERE Registry 2020 Update Impact of BMI
2616
pressure (PAP) is an effective first line treatment for to provide necessary device setting adjustments. Sleep studies
OSA,2 however, despite advancements in technology, poor performed during the annual visits do not include titration of the
compliance continues to be a major barrier to treatment.3 UAS system and the AHI reported for these visits is a total or
all-night AHI. The registry captures data on each enrolled
Upper airway stimulation (UAS) therapy is an established
patient through their first annual visit. However, the visit win-
therapy for PAP-intolerant patients. The UAS system is dow for the first annual visit can be up to 2 years post-implant to
composed of three implantable components including a allow patients to get full therapy optimization. The registry pro-
programmable implanted pulse generator (IPG), a stimula- tocol was reviewed and approved by each contributing center’s
tion lead with electrodes that are placed on the medial bra- institutional review board or ethics committee, and all patients
nches of the hypoglossal nerve, and an intercostal participating in the registry have provided informed consent.
respiratory sensing lead.4 The system is designed to sense
respiration and deliver synchronized stimulation to the
hypoglossal nerve, which causes stiffening and forward Outcome Measurements
Demographic and baseline medical history information was
protrusion of the tongue leading to the airway opening
collected for all enrolled patients. Patients completed the
during each inspiration. The efficacy of this therapy was Epworth sleepiness scale (ESS) questionnaire, a self-reported
demonstrated in the Stimulation Therapy for Apnea instrument of 8 questions that measures daytime sleepiness,
Reduction (STAR) trial.5 prior to UAS implantation and at 12-months postoperatively.
Data from patients treated with UAS as part of rou- Sleep data were captured prior to UAS implantation and the
tine clinical care have been collected in the Adherence final visit using a PSG or HSAT with one implant setting during
and Outcome of Upper Airway Stimulation for the OSA the entire night study. The final visit collected the AHI from the
International Registry (ADHERE). Previous publications entire night of the sleep study. During the post-PSG therapy
of data from the Registry reported that the use of the optimization visit and at the final visit, clinicians rated patient’s
progress using the Clinical Global Impression Index (CGI-I), a
therapy was effective in AHI reduction, patients had high
7-point scale to assess improvement or worsening of the patient’s
levels of adherence, and the majority were more satisfied OSA burden as compared to before UAS implant. Patients filled
with UAS than PAP. Review of ADHERE data found out a survey on UAS therapy satisfaction in comparison to PAP
older age and lower body mass index (BMI) associated at the post-titration and at the final visit. Therapy usage was
with therapy success. There was a trend toward women captured upon device interrogation at the post-titration and at
having increased odds of therapy effectiveness.6–8 the final visit. Safety information, including device, surgical pro-
Since the last publication, the number of the cedure, or therapy-related adverse events, was collected for the
patients in the registry has almost doubled. This work time period spanning UAS implantation through the final visit.
presents a 2020 update on registry outcomes. Further
analysis was focused on factors impacting therapy adher-
ence and therapy efficacy in BMI less than 32 kg/m2 and Statistical Analysis
those above 32 kg/m2, which were not studied in the Data from all enrolled patients (n = 1,849) and those who
STAR trial and is of interest to the clinicians. were eligible for the final visit (n = 1,019) were included as the
primary analysis cohort. A sub-analysis cohort included patients
who have completed final follow-up visit, underwent PSG or
HSAT at the final visit and had recorded baseline BMI
MATERIALS AND METHODS below 35 kg/m2 (n = 535). BMI-related outcome analysis was per-
Study Design formed by comparing two groups: patients with a baseline BMI
ADHERE (NCT02907398) is an ongoing, international, ≤32 kg/m2 (BMI32, n = 438) and patients with baseline
multicenter, observational registry designed to capture outcomes 32 < BMI ≤ 35 kg/m2 (BMI35, n = 97). Statistical significance was
of 5,000 patients implanted with the Inspire™ UAS System determined using Wilcoxon rank-sums test for non-normal data
(Inspire Medical Systems, Maple Grove, Minnesota). Manufac- and t-test for normal data with an a priori significant threshold
turer indications for implantation with the UAS system include of P < .05. If the results of the Wilcoxon rank-sum test or t-test
diagnosis of moderate to severe OSA (AHI 15–65 events/hr) with were non-significant, noninferiority testing was performed using
less than 25% central/mixed apneas, intolerance or failure of one-sided t-test for normally distributed data. The noninferiority
PAP treatment, and absence of complete concentric collapse at margin was set at five for AHI and two for ESS. The results were
the palatal level during drug-induced sleep endoscopy. reported as a mean standard deviation. Sensitivity analyses
This registry includes patients undergoing standard of care using multiple imputation method were performed to determine
management following UAS implantation without any additional the effect of missing data on the results.
intervention. All patients who undergo implant of the UAS sys-
tem are eligible to participate in the registry if they are willing
to provide consent and have a life expectancy of at least one year. RESULTS
Sites are paid for data entry for each subject. Each subject A total of 1,849 patients were enrolled at 43 global
receives a stipend for participation in the registry. Stipends are centers from October 19, 2016 to March 13, 2020. At the
paid out after visits are completed. Current UAS therapy man-
time of data analysis, implant data were available for
agement protocol includes device activation 1 month after system
1,768 patients. About 1,019 patients reached the time of
implantation, followed by patient self-adjustment for approxi-
mately 2–3 months. After self-adjustment, device optimization is 1–2 years post implant to be eligible to complete a final
recommended during an in-lab polysomnography (PSG) at 3– follow-up visit. Of these patients, 823 (83%) had com-
6 months post-implant. After initial therapy optimization, pleted a final follow up visit, 782 of these patients
patients are followed by annual visits to assess effectiveness of reported at least one of the following: AHI, ESS, Therapy
the therapy with PSG or home sleep apnea testing (HSAT) and Use, Figure 1. The population was primarily comprised of
2617
Enrolled Subjects BMI Subset
N=1849 All subjects with Baseline and

Final AHI and ESS; 15 < AHI < 65
N=535
Subjects with Implant Data
N=1768
BMI32 BMI35
N=438 N=97
Subjects 1-year post Implant
N=1019
Subjects with Final Follow-up Completed
N=823
*782 had at least one of the following

reported: AHI, ESS, Therapy Use
Fig. 1. Patient population
Caucasian (94.9%) males (73.2%) with a mean age of

TABLE I.
60.1 10.9 years and a mean BMI of 29.3 3.9 kg/m2
Patient Demographics*.
(Table I). The most prevalent co-morbidities in this population
included hypertension (46.8%), depression (23%), and diabetes Patient Characteristics All Patients BMI32 BMI35
(13.5%). Previous OSA treatments reported for this popula-
n 1,849 438 (82%) 97 (18%)
tion at baseline included PAP (97.3%), oral appliance (22.6%),
Age (yr) 60.1 10.9 59.3 11.0 60.5 9.8
adenotonsillectomy (15.3%), uvulopalatopharyngoplasty
Sex
(UPPP) (12.4%), and base of tongue surgeries (4%).
The final visit for these subjects was performed, on Male 73% 81% 76%
average, at 14.3 7.0 months post-implant. Mean ther- Female 27% 19% 24%
apy usage at the final visit was 5.6 2.2 hr/day. A signifi- Ethnicity
cant decrease in mean AHI from baseline to final visit Caucasian 95% 96% 95%
from 36.0 15.7 to 14.5 14.9 events/hr was reported, Non-Caucasian 5% 4% 5%
with a median decrease from 33.0 to 9.9 events/hr. Sensi- BMI (kg/m2) 29.3 3.9 27.7 2.7 33.4 0.9
tivity analysis using multiple imputation to account for AHI (events/hr) 36.0 15.7 35.4 14.1 37.1 14.5
missing data at final visit showed that the change in AHI ESS 11.2 5.6 11.6 5.5 12.4 5.0
from baseline to final visit was similar (Table II). Subjec-
Co-morbidities
tive improvement of symptoms was achieved with the
Hypertension 46.8% 45.0% 59.8%†
therapy use based on a mean change in ESS from
Depression 23.0% 19.4% 25.8%
11.2 5.6 to 7.1 4.6 and a median change from 11.0 to
6.0 at the final visit. Sensitivity analysis using multiple Diabetes mellitus 13.5% 9.1% 12.4%
imputation to account for missing data at final visit Atrial fibrillation 6.0% 5.7% 7.2%
showed that the change in ESS from baseline to final Anxiety 5.7% 1.1% 3.1%
visit was similar (Table II). Stroke 4.3% 5.0% 4.1%
About 151 (19%) patients with follow-up data reported Myocardial infarction 3.7% 4.6% 6.2%
therapy-related discomfort, defined as stimulation-related
*
discomfort, insomnia/arousal, or tongue abrasion. These The 535 patients included in these groups had a reported baseline
AHI ≥ 15, a BMI ≤ 35, and 1-year AHI data available.
patients had significantly lower therapy use at the final †
Significant difference between BMI groups (P = .01).
2618
TABLE II.
Summary of Results.
ALL Patients BMI32 (n = 438) BMI35 (n = 97)
12-mo data with 12-mo data with
Baseline 12-mo data with Multiple Multiple
ALL Baseline 12- Multiple Imputation Imputation Imputation
Variable (n = 1,849)* (n = 782)† mo (n = 782) (N = 1,019) Baseline 12-mo (N = 765) Baseline 12-mo (N = 155)
2
Body mass index (kg/m ) 29.3 3.9 29.2 4 29.2 4.2 27.7 2.7 27.8 2.9 33.4 0.9 33.0 2.5
(N = 415) (N = 89)
Apnea-hypopnea index N = 438 N = 97
(events/hr)
Mean 36.0 15.7 35.8 15.0 14.5 14.9 14.7 15.1 35.4 14.1 14.0 14.5 13.8 14.1 37.1 14.5 16.8 15.1 17.7 16.3
Laryngoscope 131: November 2021

Median 33.0 33.0 9.9 10 32.2 9.0 9.3 33.6 13.0 13.1
Mean change in AHI 20.9 18.3‡ 21.7 23.4‡ 21.4 18.0‡,§ 22.2 21.5‡,§ - 20.3 18.3‡,§ 21.6 20.9‡,§
from Baseline
Epworth sleepiness scale N = 384 N = 84
Mean 11.2 5.6 11.4 5.5 7.1 4.6 7.0 4.6 11.6 5.5 7.1 4.7 7.0 4.5 12.4 5.0 7.8 4.6 7.4 4.7
Median 11.0 11.0 6.0 6.3 11.0 6.0 6.1 13.0 7.0 6.9
Mean change in ESS 4.4 5.1‡ 4.3 7.1‡ 4.5 5.0‡,§ 4.4 6.0‡,§ 4.8 5.5‡,§ 4.4 6.3‡,§
from Baseline
Therapy usage (hr/day) - - 5.6 2.2 5.6 2.2 - 5.8 2.0k 5.6 2.2k - 5.2 2.2k 5.0 2.3k
(N = 380) (N = 82)
Therapy response - - 69.7% - 72.20% - 59.8%
CGI-I
Very much improved - - 42.6% - 44.6% - 40.9%
Much improved - - 35.9% - 34.1% - 31.8%
Minimally improved - - 12.3% - 12.2% - 13.6%
No change - - 6.2% - 6.4% - 8.0%
Minimally worse - - 2.1% - 2.5% - 4.6%
Much worse - - 8.0% - 0.3% - 1.1%
Patient Satisfaction
Are satisfied with UAS - - 91.2% - 90.2% - 96.0%
Would recommend - - 93.8% - 93.2% - 96.0%
UAS to others
Would choose UAS - - 92.4% - 92.1% - 93.3%
again
UAS is better than - - 91.9% - 91.7% - 89.3%
CPAP
*
All subjects with enrolled in ADHERE.
†
All subjects with a final visit (and at least one of the following reported: AHI, ESS, therapy usage).
‡
Significant change from Baseline.
§
No significant difference between BMI groups.
k
Significant difference between BMI groups.
Suurna et al.: ADHERE Registry 2020 Update Impact of BMI

2619
visit (4.9 2.5 hr/day) compared to subjects with no Therapy safety outcomes are summarized in
reported discomfort (5.7 2.1 hr/day, P = .01). Similarly, Table V. During this reporting period a total of 2.3% of
the patients who reported discomfort were found to have subjects have reported serious adverse events and 20.9%
significantly higher mean AHI at the final visit have reported nonserious adverse events. Intraoperative
(18.9 18.5 events/hr, median = 12.8) compared to sub- serious adverse events were reported in 0.43% of subjects,
jects with no reported discomfort (13.5 13.7 events/hr, including but not limited to hematoma (0.11%), infection
median = 9.2; P = .01). However, there was no significant (0.05%), and pneumothorax (0.05%). In addition, one
difference in change in AHI from baseline to final visit patient suffered intraoperative arrest (0.05%) during
between the two groups (21.2 17.1 vs. 19.3 22.0, induction of anesthesia resulting in bradycardia to the
P = .4). There was no significant difference in ESS score or 20s with no associated hypoxemia. The patient’s condi-
change in ESS in patients with or without discomfort tion stabilized after 30 seconds of chest compressions
(P = .15) (Table III). and administration of glycopyrrolate, ephedrine, and
Clinician assessment using the CGI-I at the final epinephrine. After discussion with the spouse, the deci-
visit indicated improvement in 91% of subjects. At the sion was made to proceed with the UAS implant, which
final visit, 92% of subjects stated that UAS therapy was was completed without further events. One patient suf-
better than CPAP; 92% of subjects would choose UAS fered a hypotensive event (0.05%) during the postopera-
therapy again; 94% would recommend UAS therapy to a tive period. Prior to discharge from the postoperative
friend or family member, and 91% of patients are satis- care unit, the patient was found hypotensive with sys-
fied with UAS therapy (Table II). Adjunctive therapy at tolic blood pressure in the 80s likely secondary to opi-
final visit is presented in Table IV. Ninety-one percent oids and hypovolemia. The patient was stabilized and
(91%) of subjects were using UAS therapy as their only was discharged from the hospital the following day. A
OSA therapy, with no adjunctive therapy needed. total of 35 serious adverse events (1.9%) were reported
during the post implant follow-up period, including
1 elective system explant (0.05%), 13 respiratory sensor
lead revisions (0.70%), and 12 stimulation lead revi-
TABLE III. sions (0.64%). The most common reasons for revision
UAS Outcomes Associated with Discomfort. were a respiratory sensor lead malfunction and
No Discomfort repositioning of the stimulation electrode cuff. A total
Variables at 12-mo Discomfort (n = 631) (n = 151) of 349 patients (18.9%) reported non-serious adverse
events during the follow-up period, the most common
Apnea-hypopnea index
(events/hr) events being stimulation-related discomfort (8.2%),
Mean 13.5 13.7 18.9 18.5*
insomnia/arousals (3.6%), and tongue abrasion/irrita-
tion (3.4%) (Table V).
Median 9.2 12.8
Decrease in Apnea-hypopnea index (events/hr)
Mean 21.2 17.1 19.3 22.0
Median 20.1 18.3
Epworth sleepiness scale TABLE V.
Mean 6.9 4.5 7.5 4.7 Serious Adverse Events.
Median 6.00 7.00 n events
Decrease in Epworth sleepiness scale (%
Serious Adverse Events (SAE) patients)*
Mean 4.4 5.1 4.3 5.1
Median 4.0 3.5 Intraoperative period SAEs 8 (0.43%)
Therapy Usage (hr/day) 5.7 2.1 4.9 2.5* Hematoma 2 (0.11)
* Infection 1 (0.05)
P < .05.
Implant could not be placed on the right side (separate 1 (0.05)
implant procedure to implant on the left side)
Intraoperative arrest (anesthesia-related) 1 (0.05)
TABLE IV. Obstructive event 1 (0.05)
Adjunctive Therapy at Baseline and Final Visit. Pneumothorax 1 (0.05)
Treatment Baseline 1 yr Other – unrelated 1 (0.05)
Follow-up period SAEs 35 (1.90%)
None 15 (0.8%) 372 (91.4%)
System explant (two or more components) 1 (0.05)
CPAP 1,799 (97.3%) 10 (2.5%)
System revision (two or more components) 3 (0.16)
Oral appliance 418 (22.6%) 4 (1.0%)
Sensor lead revision 13 (0.70)
UPPP 229 (12.4%) 7 (1.7%)
Stimulation lead revision 12 (0.64)
T/A for sleep apnea 283 (15.3%) -
IPG pocket revision 2 (0.11)
Base of tongue surgery 77 (4%) -
Other 4 (0.16)
Positional device Unknown 14 (3.4%)
*
Patient may have experienced more than one event.
2620
Subanalysis of Two BMI Groups visit (mean difference = 0.63, upper 97.5% confidence
BMI analyses included 535 subjects with AHI data interval = 4.3). Mean ESS in the BMI32 group decreased
collected at both baseline and final visits and enrollment from 11.6 5.5 at the baseline to 7.1 4.7 at the final
AHI between 15 and 65 events/hr. There were no other visit (a mean change of 4.5 points), whereas the mean
demographic differences between the two BMI groups. ESS in the BMI35 group decreased from 12.4 5.0 at the
Prevalence of hypertension was significantly higher in baseline to 7.8 4.6 at the final visit (a mean change of
the BMI35 group (59.8% vs. 45.0%, P = .01). No signifi- 4.8 points). The mean difference in change in ESS
cant difference between the groups was observed with between the two groups was 0.23 with the upper 97.5%
regards to other co-morbidities (Table I). The mean AHI confidence interval at 0.78 which falls within the non-
at baseline in the BMI32 group was 35.4 14.1 events/hr, inferiority margin. The results were similar after performing
compared to the mean AHI in the BMI35 group of sensitivity analyses using multiple imputation to account for
37.1 14.5 events/hr. At the final follow-up, mean AHI in missing data at final visit (mean difference = 0.16, upper
the BMI32 group was 14.0 14.5 events/hr (a change of 97.5% confidence interval = 0.91) (Table II, Fig. 2A,B). How-
21.4 events/hr), whereas the mean AHI in the BMI35 ever, there was a significant difference in surgical success
group was 16.8 15.1 events/hr (a change of 20.3 rate using the Sher criteria defined as AHI reduction by
events/hr). The change in AHI for BMI35 group was non- 50% to below 20 events/hr (72.2% in BMI32 group vs. 59.8%
inferior to the change in AHI for the BMI32 group. The in BMI35 group, P = .02). Subjects with a higher BMI were
mean difference in change in AHI between the two groups less likely to achieve an AHI < 20. There was a significant
was 1.07 with the upper 97.5% confidence interval at 4.5 difference in therapy use between the two BMI groups with
which falls within the noninferiority margin. The results patients in the BMI32 using therapy a mean of 5.8 2.0 hr/
were similar after performing sensitivity analyses using day compared to patients in the BMI35 group who used ther-
multiple imputation to account for missing data at final apy a mean of 5.2 2.2 hr/day (P = .028). Between the two
A 50.0
36.0 37.1
35.4
45.0
*p<0.05 compared to Baseline
40.0
35.0
AHI (events/h)
30.0
16.8*
14.5* 14.0*
25.0
20.0
15.0
10.0
5.0
0.0
Baseline Final Follow-up
All Subjects (n=782) BMI32 (n=438) BMI35 (n=97)
B
20 *p<0.05 compared to Baseline
11.4 11.6 12.4
15
7.1* 7.1* 7.8*
ESS
10
0
Baseline Final Follow-up
All Subjects (n=782) BMI32 (n=396) BMI35 (n=84)
Fig. 2. A, Apnea hypopnea index (AHI) change over time (by body mass index [BMI] group); B, Epworth sleepiness scale (ESS) over time
(by BMI group)
2621
100%
11% 13%
80% 19%
56% 61% 32%
60%
40%
40% 30%
20% 42% 37%

30% 25%
0%
BMI32 BMI35 BMI32 BMI35
Baseline 12 - Month
No OSA (AHI<5) Mild Moderate Severe
Fig. 3. Obstructive sleep apnea (OSA) Severity (by body mass index [BMI] group)
BMI groups, there were no differences in patient reported guard has helped address discomfort concerns related to
therapy discomfort. BMI was also not a predictor for adjunc- tongue abrasion. Overall, the rate of serious adverse events
tive therapy use. remains low. Device revision was required in 1.9% of cases,
Both BMI groups had a significant number of with the respiratory sensor lead revision being the most
patients with change in OSA severity from the baseline to common. Attention should be given to patients who report
final visit, with the percentage of patients with severe sudden change in stimulation pattern or strength, new or
OSA decreasing from 56% to 11% in the BMI32 group and worsening pain, and signs of infection at the sites of the
61% to 13% in the BMI35 group (Fig. 3) The BMI35 group implant. Device testing and appropriate imaging in such sit-
reported slightly higher adverse event rates (SAE: 4.1%; uations can help detect hardware issues.
non-SAE: 29.9%) compared to the BMI32 group (SAE: Several reports have suggested that use of adjunc-
2.3%; non-SAE: 24.7%), however, due to sample size, sta- tive therapy, such as chin strap, oral appliance, and
tistical comparison of these adverse event rates is not UPPP, can improve UAS therapy outcomes and adher-
appropriate. Clinician assessment using CGI-I and ence.9–11 Nevertheless, prior ADHERE analysis has not
patient satisfaction was similar between groups. Both demonstrated an association between other upper airway
groups had high self-reported patient satisfaction with surgeries and UAS efficacy.12 Positional OSA was also
the UAS therapy (Table II). found to not have significant impact on therapy out-
comes.13 The current ADHERE data analysis revealed
that adjunctive therapy is infrequent with 91% of
DISCUSSION patients using UAS as their only OSA treatment at final
The ADHERE registry has grown to include 1,849 par- visit. These results suggest that UAS is often effective as
ticipants worldwide. These results represent the 2020 a monotherapy, however, individualized combination
update which is the largest analysis of UAS therapy to date. therapy should still be considered in patients with sub-
Consistent with previously published therapy outcomes, optimal treatment response.
therapy use continues to demonstrate significant reduction All patients implanted in the STAR trial had a BMI
of mean AHI from 36.0 to 14.5 events/hr with normalization less than 32 kg/m2. This criterion has been required for
of ESS.5–8 Mean therapy use of 5.6 hr/day is consistent with patient selection by many insurance coverage policies,
previously reported ADHERE results.6–8 and UAS efficacy in patients with BMI > 32 kg/m2 is still
This update on therapy safety demonstrates a low debated. Potential UAS efficacy in patients with higher
rate of adverse events. Reported therapy-related discom- BMI has been suggested by Huntley et al. who reported
fort included stimulation-associated tongue abrasions and no difference in UAS therapy success rates between
insomnia/arousals that had a significant negative effect BMI > 32 kg/m2 and BMI < 32 kg/m2 groups.14 However,
on AHI reduction and therapy use. However, discomfort this study reported AHI data from 2-months PSG titra-
did not negatively affect subjective symptoms based on tion studies, as opposed to full-night AHI which is
ESS. These results suggest that assessing and addressing reported in the current ADHERE update. The data analy-
discomfort early in the postimplant care process is critical sis of the two BMI groups (BMI32 and BMI35) indicated
to long-term therapy adherence. Patients’ complaints of that although the change in AHI for patients in the
therapy discomfort during follow up visits or after PSG BMI35 group is noninferior to the change in AHI for
therapy titration should ideally be addressed immedi- patients in the BMI32 group, subjects with a higher BMI
ately. Therapy setting adjustments by changing electrode had a significantly lower likelihood in meeting Sher surgi-
configuration, therapy start delay, pulse width and fre- cal success criteria secondary to an inability to achieve an
quency can allow for more comfortable therapy use and AHI < 20 events/hr. Even though patients in both groups
potential improvements in effectiveness. Use of a dental have met DISE criteria for therapy indication, higher
2622
BMI is associated with an increase in airway closing pres- surgical success rate outcomes, AHI reduction, ESS
sure which might not be fully overcome with comfortable improvement, and therapy satisfaction are similar
UAS settings, thus leaving patients with higher residual between patients with BMI32 and BMI35. Consistent use
AHI. Analyses further indicated lower therapy usage in is imperative for therapy efficacy and is affected by dis-
patients with higher BMI. However, the higher BMI comfort. Therapy-related discomfort should be addressed
group (BMI35) experienced similar reductions in AHI and early in the process of therapy optimization to improve
there was a significant reduction of OSA severity with UAS adherence and outcomes.
UAS use. The patient-reported therapy satisfaction
with therapy was also similar for patients in both groups.
Although there was a difference in surgical success rate ACKNOWLEDGEMENTS
and therapy usage between the BMI groups, there was no We acknowledge all investigators and research coordina-
significant difference in addressing the patients’ subjective tors at 43 participating centers for their contribution of
symptoms. Reduction of sleepiness with the therapy use data collection in the ADHERE Registry.
was similar in both groups, both reporting normalization
of ESS score. These updated ADHERE results indicate
that UAS is an effective and beneficial second line treat-
CONFLICT OF INTEREST
ment for patients with moderate to severe OSA and
M.V.S. has received honoraria from Inspire Medical; A.
BMI > 32 kg/m2. It should be noted that patients in the
S. has received honoraria and covered travel expenses for
BMI35 group had higher prevalence of baseline hyperten-
invited talks on behalf of Inspire Medical; M.B. has received
sion. Considering that untreated OSA is associated with
research support and is a consultant for Inspire Medical;
increased risk of developing new-onset hypertension and is
R.D.P. has received honoraria from Inspire Medical; C.H. has
a modifiable risk factor,15 higher BMI patients should be
received research grant, travel support and consulting
considered for UAS implantation if unable to tolerate PAP.
honoraria from Inspire Medical; C.H. has received research
ADHERE continues to gather data on outcomes,
support from Inspire Medical; C.L. is a consultant for
adverse events, and therapy satisfaction in patients
Inspire Medical; J.T.M. received honoraria from ImThera
implanted with UAS as part of regular clinical care. This
Medical, is a consultant and received honoraria from
publication reports outcomes from the largest cohort of
Inspire Medical, is a consultant and received honoraria
patients using UAS to date. Lack of standardization in
from Nyxoah Medical, has received honoraria and travel
polysomnography outcomes reported by individual institu-
reimbursement from Neuwirth Medical Products; R.S.
tions has been an ongoing concern.16 The registry collects
received research support from Inspire Medical, consultant
and reports total AHI using full night PSG or HSAT at
for Smith & Nephew, Cryosa Inc, Invicta Medical, Inspire
final visit which addresses previous concerns of reporting
Medical, Galvani Bioelectronics, Enhale Medical; N.D.V. is a
only treatment AHI from the titration polysomnogram.
researcher for Inspire, Nyxoah, on medical advisory board
Nevertheless, it is not possible to mandate absolute unifor-
for Philips NightBalance; H.W. serves as the principal
mity of diagnostic testing equipment and treatment proto-
investigator of the studies with Inspire at Cleveland
cols between institutions implanting patients with OSA as
Clinic, has received funding from Resmed; E.T. has received
part of regular clinical care. The registry reports outcomes
a research grant from Inspire Medical.
only for enrolled patients who have completed final visit. A
significant portion of data for final visit AHI outcomes is
still missing, most likely related to patient noncompliance
with recommended follow-up after therapy activation. BIBLIOGRAPHY
Inability to present final visit data for every enrolled 1. Frost & Sullivan. Hidden Health Crisis Costing America Billions. Under-
diagnosing and undertreating obstructive sleep apnea draining healthcare
ADHERE patient is a limitation of the study. Even though system. American Academy of Sleep Medicine, 2016.
reasons for loss to follow-up have not yet been studied, pre- 2. Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive
sleep apnoea by continuous positive airway pressure applied through the
dominant association with either good or bad therapy nares. Lancet 1981;1:862–865.
experience can sway the reported outcomes. Nevertheless, 3. Rotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over
twenty years of data collection: a flattened curve. J Otolaryngol Head
the results reported in this publication further address fac- Neck Surg 2016;45:43.
tors that impact UAS outcomes, with special focus on 4. Heiser C, Thaler E, Soose RJ, Woodson BT, Boon M. Technical tips during
therapy-related discomfort and BMI. Although this is a implantation of selective upper airway stimulation. Laryngoscope 2018;
128:756–762.
registry study, institutions are reimbursed for their time 5. Strollo PJ Jr, Soose RJ, Maurer JT, et al. Upper-airway stimulation for
to record the data in the study database. In addition, mul- obstructive sleep apnea. N Engl J Med 2014;370:139–149.
6. Boon M, Huntley C, Steffen A, et al. Upper airway stimulation for obstruc-
tiple physicians who have contributed to the data pres- tive sleep apnea: results from the ADHERE Registry. Otolaryngol Head
ented in this manuscript have received honoraria from the Neck Surg 2018;159:379–385.
7. Heiser C, Steffen A, Boon M, et al. Post-approval upper airway stimulation
registry sponsor, which is a potential source of bias and predictors of treatment effectiveness in the ADHERE registry. Eur Respir
limitation of the study. J 2019;53:1801405.
8. Thaler E, Schwab R, Maurer J, et al. Results of the ADHERE upper airway
stimulation registry and predictors of therapy efficacy. Laryngoscope
2020;130:1333–1338.
9. Ramaswamy AT, Li C, Suurna MV. A case of hypoglossal nerve stimulator-
CONCLUSION resistant obstructive sleep apnea cured with the addition of a chin strap.
This interval update on ADHERE registry outcomes Laryngoscope 2018;128:1727–1729.
10. Lee JJ, Sahu N, Rogers R, Soose RJ. Severe obstructive sleep apnea treated
demonstrates efficacy, safety, and high adherence rates with combination hypoglossal nerve stimulation and oral appliance ther-
for UAS therapy. Although there are differences in Sher apy. J Dental Sleep Med 2015;2:185–186.
2623
11. Steffen A, Abrams N, Suurna MV, Wollenberg B, Hasselbacher K. Upper- 14. Huntley C, Steffen A, Doghramji K, Hofauer B, Heiser C, Boon M. Upper
airway-stimulation before, after or without uvulopalatopharyngoplasty - a Airway Stimulation in Patients with Obstructive Sleep Apnea and an Ele-
two-year perspective. Laryngoscope 2019;129:514–518. vated Body Mass Index: A Multi-institutional Review. Laryngoscope 2018;
12. Kezirian EJ, Heiser C, Steffen A, et al. Previous surgery and hypoglossal 128:2425–2428.
nerve stimulation for obstructive sleep apnea. Otolaryngol Head Neck 15. Marin JM, Agusti A, Villar I, et al. Association between treated and
Surg 2019;161:897–903. untreated obstructive sleep apnea and risk of hypertension. JAMA 2012;
13. Steffen A, Hartmann JT, König IR, Ravesloot MJL, Hofauer B, Heiser C. Evalu- 307:2169–2176.
ation of body position in upper airway stimulation for obstructive sleep apnea- 16. Dedhia RC, Woodson BT. Standardized reporting for hypoglossal nerve
is continuous voltage sufficient enough? Sleep Breath 2018;22:1207–1212. stimulation outcomes. J Clin Sleep Med 2018;14:1835–1836.
2624

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Adult Sleep Apnea

© Copyright 2022. AAO‐HNSF FLEX xRead: April 2022 1|P a g e

EBM Level: 4 – Systematic Review

© Copyright 2022. AAO‐HNSF FLEX xRead: April 2022 2|P a g e

EBM Level: 4 – Systematic Review

EBM Level: 2 – Randomized Trial

© Copyright 2022. AAO‐HNSF FLEX xRead: April 2022 3|P a g e

© Copyright 2022. AAO‐HNSF FLEX xRead: April 2022 4|P a g e

Tongue Suspension: An Evidence-Based Review and Comparison to

INTRODUCTION Continuous positive airway pressure (CPAP) is cur-

Summary and Grading of Clinical Data

14 35.0 17.0 29 2 months (RDI) DeRowe et al., 2000 4 MM unknown 2

15 31.3 38.7 21.0 20 3–6 months Miller, et al. 2002 4 CM, MM II 2

23 27.5 40.7 15.4 87 6 months Emara et al., 2011 4 CM, MM, E II 0

Tongue Suspension 1 UPPP Level 2 5 2; Level 4 5 6 C 104/167 62.3 N/A N/A

Published in final edited form as:

Drug-Induced Sleep Endoscopy and Hypoglossal Nerve

David T Kent, MD,

Department of Otolaryngology–Head and Neck Surgery, Vanderbilt University Medical Center,

Mark A D’Agostino, MD,

Katherine K Green, MD, MS,

Ryan J Soose, MD,

Medicine, Pittsburgh, Pennsylvania, USA

Thomas M Kaffenberger, MD,

B Tucker Woodson, MD,

Colin Huntley, MD,

Maurits S Boon, MD,

Clemens Heiser, MD,

Department of Otorhinolaryngology, Head and Neck Surgery, Technische Universität München,

Amelie Birk, MD,

Maria V Suurna, MD,

Ho-Sheng Lin, MD,

Jonathan A Waxman, MD PhD,

Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of

Eric J Kezirian, MD MPH

Study Design: Retrospective, multicenter cohort study

Setting: Academic medical centers

Conclusions: DISE findings of primary tongue or velum contributions to airway obstruction

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

as a mandatory component of the pre-operative evaluation after Vanderveken et al.

of preoperative DISE and outcomes of HNS in a large multicenter cohort.

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

velum-related obstruction (p=0.035). There was no association between epiglottis-related

obstruction and outcomes.

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Velum-related obstruction responded well to HNS with notable improvements in AHI

There was no statistically-significant association between outcomes and complete concentric

potential confounders, including a change in implant technique between subgroups, moving

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Funding and Conflicts of Interest:

977. [PubMed: 26980916]

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Distribution of study participants across centers

Center No. Study Participants (n=343) Percent of Total Cohort

Laryngoscope. Author manuscript; available in PMC 2021 August 13.

Age at surgery, years 60.4 ± 11.0 59.3 ± 10.4