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.

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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.

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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.

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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
characterized by partial or complete collapse of the
upper airway.1 This occurs secondary to inadequate tone
of the tongue and/or dilator muscles of the upper airway.
In the United States, the prevalence of OSA is approxi-
mately 2% to 5% in women and 3% to 7% in men.2 The
sequelae of untreated OSA have been well documented.
Multiple studies have linked conditions including
hypertension, cerebrovascular accident, neurocognitive
impairment, motor vehicle accidents, abdominal aortic
aneurysm enlargement, and insulin resistance to
untreated OSA.2–9
From the Department of Head and Neck Surgery (E.HANDLER), Kai-
ser Permanente, Oakland, California, U.S.A.; the Department of Otorhi-
nolaryngology, Head and Neck Surgery (E.HAMANS), Multidisciplinary
Sleep Center, University Hospital Antwerp, Edegem, Belgium; the San
Francisco, Department of Otolaryngology–Head and Neck Surgery
(A.N.G.), University of California, San Francisco, California; and the
Advanced Ear, Nose & Throat Specialists (S.M.), PC, Atlanta, Georgia,
U.S.A.
Editor’s Note: This Manuscript was accepted for publication April
15, 2013.
Disclosures: Philips (E.HAMANS); ApniCure (A.N.G.); Siesta Medical
(E.HANDLER, A.N.G., S.M.). The authors have no other funding, financial
relationships, or conflicts of interest to disclose.
Send correspondence to Ethan B. Handler, MD, Kaiser Perma-
nente–Department of Head and Neck Surgery, Oakland, California,
94105. E-mail: ehandler81@gmail.com
DOI: 10.1002/lary.24187
rently considered the first-line treatment for OSA. It has
shown to improve symptoms, normalize the risk of traf-
fic and work accidents, normalize mortality in
severe OSA, and reduce the risk of cardiovascular inci-
dents.10–12 Aside from tracheotomy, a CPAP device
serves as the best therapy to treat OSA, yet outcomes
are strictly tied to compliance. Discomfort of the mask
and feelings of suffocation, noise, and discomfort of the
apparatus are a few reasons that patients abandon the
device. Short- and long-term compliance of CPAP has
been estimated between 40% to 80% as patients often
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
group of CPAP-compliant patients, the mean AHI under
treatment was still above 10.16
Obstructive sleep apnea is a multilevel disease;
thus, determining the anatomical and physiological site
of obstruction is critical for matching a patient to the
appropriate surgical intervention(s). Various systems
have been suggested to better categorize the level of
obstruction, including the Fujita classification, Friedman
staging, and more recently, drug-induced sleep endos-
copy (DISE).17–19 In his 10-year retrospective audit,
Kotecha et al.20 first documented the efficacy of DISE
with regard to diagnosing the appropriate level of
obstruction and found that surgical outcomes correlated
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.
Hierarchy From Oxford Center for Evidence-Based Medicine.
Level of Evidence Study Design
1 Randomized, controlled trial
2 Cohort study
3 Case-control study
4 Case series
5 Expert opinion
consensus is that patients with hypopharyngeal obstruc-
tion in addition to retropalatal obstruction are unlikely
to be improved by retropalatal surgery alone. Further-
more, the practice of a patient-specific operative
approach to level of obstruction is gaining acceptance
among sleep apnea surgeons.
Uvulopalatopharyngoplasty (UPPP) is the most
widely performed operation for OSA, although its lack of
efficacy for hypopharyngeal obstruction has been widely
documented. Success rates range within the literature
from 30% to 78%, and these studies are often con-
founded with selection bias.21 At this time, there is no
consensus for which procedure is best used to address
hypopharyngeal obstruction in OSA.21,22
Tongue base procedures that do not remove tissue
aim to tether the tongue via sutures/ribbons/barbs to the
mandible, or to advance the tongue via mandibular oste-
otomies. The purpose is to enlarge the hypopharyngeal
airway in the anterior to posterior dimension. Proce-
dures targeting the hypopharynx have been hotly
debated over the past few years, making this operation
an ideal one to review.
The first objective of this study was to perform an
evidence-based medicine (EBM) review, based on the
Center for Evidence Based Medicine guidelines, of the
minimally invasive suture-based tongue suspension pro-
cedure as a stand-alone therapy for hypopharyngeal
obstruction in OSA to evaluate its baseline safety and
effectiveness. A second objective was to compare out-
comes of tongue suspension as part of a multilevel
approach to OSA surgery to an EBM review of genioglos-
sus advancement (GA) with uvulopalatopharyngoplasty
(UPPP), and of genioglossus advancement with hyoid
suspension (GAHM) with UPPP (operations considered
the accepted standard for hypopharyngeal obstruction).
MATERIALS AND METHODS
We used multiple search methods, including queries of
PubMed, to identify the four cohorts of surgical patients as
described below.
The first search was to identify tongue suspension proce-
dures as a stand-alone therapy for OSA. A PubMed search for
“tongue suspension” was performed in October 2012, resulting
in 195 potential articles. Articles were excluded from this pool
for the following reasons:
 The publication was a letter or comment.
 A tongue suspension procedure was not performed as part of
the methods.
 An additional airway surgery was performed along with the
tongue suspension.
Laryngoscope 124: January 2014
330
 The clinical indication was unrelated to OSA and/or snoring.
 The language was not in English.
 The article was published before 1998.
The second search was used to identify tongue suspension
procedures as part of a multilevel approach to treat OSA. A
PubMed search for “tongue suspension” was performed in Octo-
ber 2012, resulting in 195 potential articles. Articles were
excluded from this pool for the following reasons:
 The publication was a letter or comment.
 A tongue suspension procedure was not performed as part of
the methods.
 The procedure was performed without UPPP.
 The clinical indication was unrelated to OSA and/or snoring.
 The language was not in English.
 The article was published before 1998.
The third search was used to identify both cohorts that
included genioglossus advancement (GA) with UPPP and genio-
glossus plus hyoid suspension (GAHM) with UPPP. A PubMed
search for “genioglossus advancement” was performed in Octo-
ber 2012, resulting in 75 potential articles. Articles were
excluded from this pool for the following reasons:
 The publication was a letter or comment.
 A genioglossus advancement procedure was not performed
as part of the methods.
 The clinical indication was unrelated to OSA and/or snoring.
 The language was not English.
 The same patient results from another identified article
were being reported upon.
 The article was published before 1990.
Lastly, only data where the surgical interventions were
performed simultaneously (not staged) were included (e.g., if a
UPPP and GA were performed in one operation and a hyoid
suspension was subsequently performed on the failures from
the first combined operation, only the results from the
GA 1 UPPP were reported and the “staged” results for the
GA 1 HS 1 UPPP were discarded).
To identify additional applicable literature articles, a
PubMed search for “genioglossal advancement” was performed
also in October 2012, resulting in 14 potential articles. Articles
were excluded from this pool for the same reasons given above.
Lastly, the bibliography of the most recent (2006) review
of hypopharyngeal sleep surgery,23 the most recent (2008)
review on multilevel sleep surgery,24 and two reviews of non-
pressure sleep apnea therapies21,25 were analyzed for potential
publications missed in the above PubMed searches for all
inquiries.
Summary and Grading of Clinical Data
Unless otherwise noted, the definition of surgical success
selected is the same as used by Sher et al.,26 where a positive
response is defined as a 50% decrease in the respiratory dis-
turbance index (RDI) or apnea-hypopnea index (AHI) and a
postoperative RDI or AHI < 20. For purposes of this review, RDI
and AHI are used interchangeably in defining surgical out-
comes and success.
To grade the quality of each article’s research evidence, a
simplified format based on the evidence hierarchy at the Oxford
Centre for Evidence-based Medicine was used.27 This grading
system is given in Table I.
In this analysis, studies have been individually reviewed
and also combined to analyze the overall safety and effective-
ness of the treatment. The strength of the combined conclusion
Handler et al.: EBM Review of Tongue Suspension for OSA
 TABLE II.
Grades Corresponding to Levels of Evidence.
Grade of
Conclusion Supporting Evidence
A Consistent level 1
B Consistent level 2 or 3 or extrapolation
from level 1
C Level 4 or extrapolation from level 2 or 3
D Level 5 or troubling, inconsistent, or
inconclusive studies of any level of evidence
of this review is dependent on the quality of the available evi-
dence. Table II presents the grades that correspond to the levels
of evidence on which the conclusions are based.
Consistent with the (2006) review of hypopharyngeal sleep
surgery,23 we then compared the results for each procedure or
each combination of procedures according to the criteria for a
successful surgical outcome as outlined. We used the v2 test to
determine whether there was a difference in the share of
patients with a successful outcome among treatments, and
P < 0.05 was considered statistically significant.
RESULTS
A total of 27 studies was gathered for comparison.
The first literature review performed to identify tongue
suspension as a stand-alone procedure to treat OSA
yielded six publications.28–33 The results are presented
in Table III. A total of 82 patients were identified with
an average body mass index (BMI) of 29.4. Average pre-
operative and postoperative AHI was 32.0 and 18.8
(41.1% reduction), respectively. Based on the measure of
surgical success defined previously, this resulted in a
surgical success rate of 36.6%. Postoperative follow-up is
listed and ranges from 2 months to 2 years. There was
one level 2 study, and five of level 4 studies. The data
listed from Kuhnel30 and Fibbi29 are listed twice,
representing two different follow-up periods for their
patients. Both Kuhnel30 and DeRowe28 had a total of
three patients between the two studies who needed re-
moval of the tongue suspension suture. The causes cited
within those publications were infection and pain, which
promptly resolved with removal of the tongue suture.
The last two studies on this list, performed by Fibbi and
Sezen, yielded better success rates than the earlier ones.
Sezen and Fibbi chose patients with almost 50% lower
preoperative AHI when compared to the earlier studies.
Sezen also described lower suture placement with
tighter suspension, a technique that may have yielded
better results.
The second literature review performed to identify
tongue suspension in conjunction with UPPP to treat
OSA yielded eight publications.31,34–40 The results are
presented in Table IV. A total of 167 patients were iden-
tified with an average BMI of 29.9. Average preoperative
and postoperative AHI was 44.0 and 16.6 (62.3% reduc-
tion), respectively. Based on the measure of surgical suc-
cess defined previously, this resulted in a surgical
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-
dence. There were three patients among the cohort who
had a reversal of their procedure. One patient had
extrusion of the suture; another patient at 2 months fol-
low-up had broken the suture; and the third patient had
persistent globus sensation, which resolved with suture
removal.
The third literature review performed to identify
genioglossus advancement with UPPP, with or without
hyoid suspension myotomy to treat OSA, yielded 18 pub-
lications.39,41–56 The results presented in Table V show
the cohort of GA 1 UPPP, and the results in Table VI
show the cohort of GAHM 1 UPPP.
A total of 151 patients were identified in the cohort
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.

Laryngoscope 124: January 2014 Handler et al.: EBM Review of Tongue Suspension for OSA
331
 TABLE IV.
Suture-Based Tongue Suspension Combined with Uvulopalatopharyngoplasty (UPPP).

AHI Patients
Surgical 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

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.
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); TS 5 tongue suspension.

preoperative and postoperative AHI was 53.2 and 23.8
(55.3% reduction), respectively. Based on the measure of
surgical success defined previously, this resulted in a
surgical success rate of 61.1%. Postoperative follow-up is
listed and ranges from 3 to 10 months. There was one
article of level 2 evidence, and six articles of level 4 evi-
dence. Complications included tooth root injury, mild
transient dripping of saliva and numbness of the chin,
wound infections, and mandible fractures.
A total of 467 patients were identified in the cohort
of GAHM 1 UPPP, with an average BMI of 29.9. Average
preoperative and postoperative AHI was 54.6 and 22.7
(58.4% reduction), respectively. Based on the measure of
surgical success defined previously, this resulted in a
surgical success rate of 61.1%. Postoperative follow-up is
listed and ranges from 3 months to 4 years. All articles
were level 4 evidence. Complications were similar to
genioglossus advancement, with the addition of tran-
sient dysphagia and wound dehiscence.
The published studies are summarized in Table VII
according to the listed procedures or combination
thereof. Consistent with the most recent (2006) review of
hypopharyngeal sleep surgery,23 the evidence supports a
grade C recommendation. The pre- and postoperative
AHI and definition of surgical success as defined above
serve as the primary mode of comparison between
patient groups. Surgical success rates for all the studies
reviewed varied widely (0% to 87%). Results of a v2 test
showed that, when aggregated data are used to compare
suture-based tongue suspension with UPPP for hypo-
pharyngeal obstruction in OSA against genioglossal
advancement with UPPP and GAHM with UPPP,
there is no difference in reported outcome of surgical
success.

TABLE V.
Genioglossus Advancement With Uvulopalatopharyngoplasty.
AHI/RDI
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

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.

Laryngoscope 124: January 2014 Handler et al.: EBM Review of Tongue Suspension for OSA
332
 TABLE VI.
Genioglossus Advancement, Hyoid Myotomy, and Uvulopalatopharyngoplasty.
AHI
Surgical Patients With
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.
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, 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
of patient characteristics, including BMI, pre and post
AHI, surgical success rate, duration of follow-up, type of
hypopharyngeal obstruction as described by Fujita,18
and patients with reversed therapy.
DISCUSSION
Our literature review of tongue advancement sur-
gery for sleep apnea is the most recent since the (2006)
review.23 Our article sought to narrow the focus to com-
pare tongue suspension against an “accepted standard”
for hypopharyngeal surgery, genioglossus advancement
with UPPP, with or without hyoid suspension. A similar
comparison is made in the previous review, but results
from tongue suspension with and without UPPP are
grouped together and compared to GAHM with UPPP,
thus diluting the actual success rate of tongue suspen-
sion with UPPP for multilevel sleep surgery.
Surgical treatments of the tongue base and hypo-
pharyngeal collapse include lingual tonsillectomy, hyoid
suspension, midline glossectomy, radiofrequency abla-
tion, mandibular osteotomy with genioglossus advance-
ment, and maxilo-mandibular advancement. Many of
these procedures are associated with significant morbid-
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
procedures, followed by a reasonable recovery and
return to work/life. Traditionally, obstructive sleep apnea
surgery has not followed this paradigm. Recovery from
palate and hypopharyngeal surgery is painful, and time
away from work can extend up to 3 weeks.
The Repose Surgical Kit (CKA AirVance, Medtronic,
Inc.) was one of the first devices aimed at the tongue
base and considered minimally invasive. The ease of use
and preliminary clinical data was documented with two
initial articles, one by Woodson et al.33 and a second by
DeRowe et al.28 Woodson reported on a patient popula-
tion of snorers and mild to moderate sleep apneics, most
of whom had failed UPPP. He found symptomatic
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.

Laryngoscope 124: January 2014 Handler et al.: EBM Review of Tongue Suspension for OSA
333
effect on AHI/RDI. His support for tongue suspension
was in conjunction with other OSA procedures in a mul-
tilevel approach. The most common complication was
delayed infection of the suture, thought to be due to
inadequate coverage of oral flora in the perioperative
and postoperative periods. In patients where discomfort
or infection persisted, removal of the suture was easy
and the reversibility cited as an advantage of this tech-
nique. DeRowe had better success with the Repose sys-
tem. This trial enrolled 16 patients, excluding those
with a BMI over 35 and an RDI above 70 or below 12.5.
They noted a significant drop in RDI postoperatively, as
well as documented snoring improvement by bed part-
ners. The complications included a floor of mouth cyst
that resolved with marsupialization. The other com-
plaints were related to postoperative pain that subsided
within 1 to 2 weeks. This article also supported tongue
suspension/stabilization as a minimally invasive adjunct
to other sleep apnea operations to appropriately satisfy
the multilevel approach.
Since these initial studies, treating the tongue base
has garnered momentum among practitioners. New tech-
niques and devices are currently being developed that
aim to improve the efficacy and reduce the morbidity of
hypopharyngeal interventions. Hypoglossal nerve stimu-
lation implants have been developed, and three competing
companies (Inspire Medical, Inc., Apnex Medical, Inc.,
Imthera, Inc.) are currently working on clinical trials.
These devices target lingual advancement by stimulating
the hypoglossal nerve during sleep. Early results for these
devices have been published and appear promising.57
The Repose system requires a transoral suture
placed through the mucosa at the tongue base. An
anchor screw is placed on the inner cortex of the mandi-
ble, originally performed through a floor of mouth inci-
sion, although most surgeons now use a submental
incision for access. An adjustable tongue suspension de-
vice was developed by Aspire Medical Inc., which
included a tongue anchor and a tetherline to suspend
the tongue. This device was reviewed in three trials con-
ducted by Hamas et al.,58 Woodson et al.,59 and Pave-
lec.60 This device is not currently available for use due
to breakage of the anchor over time. The Encore System
(Siesta Medical) is a newer adjustable and multilevel
tongue suspension device. It includes two tongue suspen-
sion/stabilization ribbons that utilize small screws on
the lingual cortex, which allows for chronic adjustment
of ribbon tension, as well as a suture passer that allows
for easy placement of the suspension ribbon within the
genioglossus muscle without passing through the mu-
cosa. The incision is hidden well beneath the submental
crease.
Suture migration has been discussed as a potential
reason for lack of tongue suspension efficacy over time,
although this has not been proven.32,33,35 Vincente et al.
has had the longest follow-up period to date at 3 years. A
total of 54 patients were followed during this time period,
with a 78% surgical success rate as defined by a greater
than 50% reduction in AHI and an AHI < 20. They per-
formed tongue suspension as part of a multilevel surgery
with UPPP. It was noted that the best response was
Laryngoscope 124: January 2014
334
obtained in patients with a BMI < 35 kg/m2.40 This article
suggests long-term efficacy of tongue suspension in con-
junction with UPPP. Suture migration may occur to some
degree as the suture or ribbon obtains equilibrium with
the tongue musculature, but what is difficult to ascertain
is if this migration is solely responsible for a worsening
AHI years after the surgical intervention. Other con-
founding variables likely play a role, such as weight gain
and sleep habits. The Encore System has a radio-opaque
marker so that an assessment of suture migration can be
accurately assessed over years of follow-up with a lateral
cephalogram.
As newer studies regarding CPAP compliance
emerge, physicians will face a surge in patients seeking
definitive surgical treatment. A recent study reporting
outcomes of long-term CPAP compliance and AHI reduc-
tion discovered a few important points. First, that even in
an ideal and carefully selected group of CPAP patients,
CPAP cannot completely eliminate respiratory events due
to limited adherence. Second, when the reduction of the
AHI is used as the criteria for treatment success, adher-
ence needs to be taken into account when comparing
CPAP with alternative methods, especially those with
100% compliance such as surgery. Lastly, defining treat-
ment success as an AHI <5 is inappropriate; even CPAP,
which is considered the gold standard of treatment, is
unable to achieve these results under everyday conditions
when adherence is taken into account.16 In contrast, stud-
ies are lacking with regard to long-term outcomes of mor-
bidity and mortality, as defined by a successful sleep
operation yielding a >50% drop in AHI with an AHI < 20.
As surgeons, we need to hold ourselves to a higher stand-
ard of defining success, both short term and long term,
and evaluating the benefit of any reduction in AHI
through further studies. The paradigm of successful sleep
apnea treatment is evolving; and as more patients seek
surgical intervention it is important to provide minimally
invasive multilevel options, including tongue suspension.
There are some limitations of our current review.
Patient demographic data for each individual study was
not available for review; as such, a t test comparison
that draws from the average data among all patients,
including the standard deviation, could not be used to
measure statistical significance within each study and
across the aggregated study groups. Second, of the 27
total studies used to create our surgical cohorts, three
were of level 2 evidence; the remaining 24 were consid-
ered level 4. Unfortunately, this pattern is a reflection of
studies performed within surgery and surgical subspe-
cialties, recognizing the inherent difficulty of randomiz-
ing patients to different surgical interventions or sham
surgery to create a control group. Dominated within the
searchable publications are articles citing mainly level 3
and 4 evidence in contrast to preferred randomized con-
trol trials. Last, in compiling the various studies for our
review based on our strict search criteria, we found
some of the studies used pre- and postoperative respira-
tory distress index (RDI), while others used the apnea-
hypopnea index (AHI). This has potential to impact the
weighted averages, although consistency within each
study serves as its own control.
Handler et al.: EBM Review of Tongue Suspension for OSA
 It is worth mentioning that the average results
from GA 1 UPPP compared to GAHM 1 UPPP are simi-
lar. One would assume that the addition of hyoid sus-
pension to the procedure would yield better results.
There was approximately three times the number of
patients in the GAHM 1 UPPP cohort. The average BMI
and preoperative AHI was 1 point higher in this group
as well. The choice for the additional hyoid suspension
was likely a judgment call of the sleep surgeon, but fur-
ther controlled studies with randomization may be able
to discern if hyoid suspension does indeed make a
difference.
Developing a specific patient plan for treating sleep
apnea is paramount in predicting success of the proce-
dures chosen.22 In addition to physical exam, diagnostic
tests such as fiberoptic nasopharyngoscopy, and more
recently drug-induced sleep endoscopy (DISE), has
empowered physicians to objectively document the level
of obstruction.19,20 Our literature review fulfilled both
stated objectives. First, as a stand-alone procedure for
tongue base obstruction, tongue suspension showed a
success rate in approximately one-third of patients. Sec-
ond, tongue suspension as part of a multilevel approach
to sleep apnea surgery has similar success to the
“accepted standard” procedure of GAHM plus UPPP.
Thus, tongue suspension is a viable alternative to treat-
ing the tongue base with a lesser degree of morbidity,
and with the advantage of reversibility if not successful.
CONCLUSION
Tongue suspension is effective and safe as part of a
multilevel surgical approach for patients with OSA.
When paired with UPPP, tongue base suspension has an
average surgical success rate of 62.3%, with results as
high as 81% in appropriately selected patients. As a
stand-alone procedure, its success rate is 36.6%, compa-
rable to UPPP procedures for OSA success rates across
the board. Tongue suspension is minimally invasive and
reversible, and in multilevel surgery as efficacious as
the more morbid and invasive genioglossus advancement
with or without hyoid suspension. Tongue suspension
should be considered in patients with OSA who demon-
strate tongue base obstruction.
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 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, Phillip_Huyett@meei.harvard.edu.
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

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

 Huyett et al. Page 3

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
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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

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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
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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),
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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.

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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

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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

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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

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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

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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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10. Green KK, Kent DT, D’Agostino MAet al.Drug-Induced Sleep Endoscopy and Surgical Outcomes:
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15. Dedhia RC, Woodson BT. Standardized Reporting for Hypoglossal Nerve Stimulation Outcomes. J
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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)
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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
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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

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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

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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

Complete vs partial/none −24.4 ± 15.8 vs −24.7 ± 16.8 0.94

Any vs none −26.2 ± 16.8 vs −23.8 ± 16.6 0.19

Complete vs none −24.4 ± 15.8 vs −23.8 ± 16.6 0.83

T None vs partial vs complete −23.4 ± 18.7 vs −26.5 ± 16.7 vs −23.8 ± 15.5

Complete vs partial/none −23.8 ± 15.5 vs −25.3 ± 17.5 0.40

Any vs none −25.0 ± 16.1 vs −23.4 ± 18.7 0.47

Complete vs none −23.8 ± 15.5 vs −23.4 ± 18.7 0.87

E None vs partial vs complete −24.6 ± 16.7 vs −25.0 ± 14.3 vs −25.0 ± 21.6

Complete vs partial/none −25.0 ± 21.6 vs −24.6 ± 16.5 0.93

Any vs none −25.0 ± 16.8 vs −24.6 ± 16.7 0.87

Complete vs none −25.0 ± 21.6 vs −24.6 ± 16.7 0.92

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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
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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

Complete vs partial/none 19 (57.8%) vs 230 (74.2%) 0.042

Any vs none 86 (69.9%) vs 163 (74.1%) 0.41
Author Manuscript

Complete vs none 19 (57.8%) vs 163 (74.1%) 0.049

T None vs partial vs complete 48 (64.9%) vs 86 (70.5%) vs 115 (78.2%) 0.09

Complete vs partial/none 115 (78.2%) vs 134 (68.4%) 0.043

Any vs none 201 (74.7%) vs 48 (64.9%) 0.09

Complete vs none 115 (78.2%) vs 48 (64.9%) 0.033

E None vs partial vs complete 216 (73.5%) vs 24 (72.7%) vs 9 (56.3%) 0.32

Complete vs partial/none 9 (56.3%) vs 240 (73.4%) 0.13

Any vs none 33 (67.3%) vs 216 (73.5%) 0.37

Complete vs none 9 (56.3%) vs 216 (73.5%) 0.13

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
Author Manuscript

obstruction.

DISE = drug induced sleep endoscopy, V = velum, CCC= complete concentric collapse, O = oropharyngeal lateral walls, T = tongue, E = epiglottis
Author Manuscript

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

 Huyett et al. Page 17

Table 7.

Surgical response according to DISE primary structure contributing to airway obstruction.

Author Manuscript

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
Author Manuscript
Author Manuscript
Author Manuscript

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

 Huyett et al. Page 18

Table 8.

Logistic regression analyses for odds ratios reflecting association between surgical response (tPSG) and
Author Manuscript

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)

Author Manuscript

BMI = body mass index; CI = confidence interval.

Author Manuscript
Author Manuscript

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

 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
published 2010 American Academy of Sleep Medicine (AASM)
guideline on the use of surgery to treat adults with obstructive sleep
apnea (OSA)1 and reflects the current recommendations of the
AASM. Positive airway pressure (PAP) is well recognized as the
most efficacious treatment for OSA, but therapy effectiveness
may be compromised when patients are unable to sufficiently
adhere to therapy or obtain adequate benefit. For some patients
struggling with PAP, surgery may therefore be a less efficacious
yet ultimately a more effective treatment option. The 2010 guide-
line made recommendations for specific surgical procedures, but it
did not address the critical question of when to consider surgical
treatment options.1 The current guideline seeks to recognize clini-
cal scenarios where such compromises should be discussed and to
provide a framework for explicitly addressing the role of patient-
specific values and preferences in the creation of a customized
treatment plan evaluating the risks, benefits, costs, and side effects
associated with various medical and surgical therapies.
available evidence and is designed to provide recommenda-
tions for when health care providers treating OSA should dis-
cuss referral for upper airway or bariatric surgery evaluation
with adult patients with OSA. It intentionally does not provide
recommendations for individual surgical procedures and
instead focuses on the body of evidence surrounding surgery
as a treatment option in the setting of residual or untreated
OSA. It informs clinical care by considering specific, com-
monly encountered clinical scenarios in which consideration
of surgery may provide patient benefit, acknowledging that
the tools and knowledge base needed for comprehensive
anatomic evaluation and patient counseling regarding the sur-
gical experience are outside the practice boundaries of most
health care providers. Procedural selection is a complex deci-
sion requiring an informed discussion of risks and benefits
surrounding anatomically appropriate options that incorporates
patient-specific values and preferences. Collaborative commu-
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.
referring health care provider, leveraging each one’s areas of
expertise, is the management pathway most likely to yield sat-
isfactory outcomes.
This guideline utilizes available evidence to support recom-
mendations regarding discussion of referral in the following
scenarios:
(1) Patients who are intolerant or unaccepting of PAP therapy
(2) Patients who have persistent inadequate PAP adherence
due to pressure-related side effects
(3) Patients with obvious upper airway anatomic abnor-
malities potentially amenable to surgery as initial OSA
treatment
The treatment of adults with OSA should be based on a diagnosis of
OSA established using objective testing performed in
conjunction with a comprehensive sleep evaluation. For this guide-
line, the terminology “discuss referral” implies a discussion
between the patient and health care provider regarding the option
of surgical consultation as part of a comprehensive discussion of
alternative treatment options to PAP. Under ideal circumstances,
patients with inadequate PAP utilization will have had an opportu-
nity to consult with a sleep medicine professional to address bar-
riers to adherence, although access to such resources may be
Downloaded from jcsm.aasm.org by 64.124.192.2 on January 25, 2022. For personal use only. No other uses without permission.
limited in some areas.3 A threshold for adequate PAP adherence
will vary between patients depending on their individual underly-
ing medical history, symptomatology, disease severity, and
response to PAP, and should be part of the discussion between
the health care provider and patient. “Sleep surgeon” refers to an
otolaryngologist or oral and maxillofacial surgeon with training
and expertise in upper airway surgery who has an appropriate
understanding of sleep medicine and modern surgical techniques
for the treatment of OSA. If the patient elects for referral, the
standard surgical consultation includes a detailed anatomic assess-
ment for surgical treatment occasionally using tools unavailable to
the average health care provider, such as flexible fiber-optic laryn-
goscopy. A discussion of the individual’s expected risks and bene-
fits of each appropriate treatment option is part of the standard
Copyright 2022 American Academy of Sleep Medicine. All rights reserved.
informed consent process with the surgeon, including the risk of
residual OSA. Following the principle of primum non nocere
(“First, do no harm”), it is expected that surgery proceed only
once the surgeon and patient have mutually agreed upon an accept-
able risk profile. Inherent to this evaluation is the understanding
that somereferred patients willnot beappropriatefor surgical inter-
ventions and are expected to be counseled as such by surgical col-
leagues. It is additionally understood that many patients will
ultimately elect against surgical therapy after an informed discus-
sion with a surgeon. These individuals should be referred back to
the health care provider for further OSA management. All patients
should receive follow-up care to re-evaluate OSA symptoms;
residual sleep-related symptoms, including residual sleep-
disordered breathing, should be evaluated and addressed.
METHODS
The AASM commissioned a task force (TF) of experts in sleep
medicine, otolaryngology, and bariatric surgery to develop this
Journal of Clinical Sleep Medicine, Vol. 17, No. 12
Referral of adults with OSA for surgical consultation
guideline and the supporting systematic review. Members of
the TF were required to disclose all potential conflicts of interest
(COI), per the AASM’s COI policy, prior to being appointed to
the TF and throughout the research and writing of these docu-
ments. In accordance with the AASM’s conflicts of interest pol-
icy, TF members with a Level 1 conflict were not allowed to
participate. TF members with a Level 2 conflict were required
to recuse themselves from any related discussion or writing
responsibilities. All relevant conflicts of interest are listed in
the Disclosures section.
The TF conducted a systematic review of the published scien-
tific literature, focusing on patient-oriented, clinically relevant
outcomes to answer 4 PICO (Patient, Intervention, Comparison,
and Outcomes) questions regarding the surgical treatment of
adults with OSA. This review was designed to determine if surgi-
cal therapies for OSA are effective for improving outcomes of
interest when analyzed collectively, which will inform recom-
mendations for when health care providers treating OSA (subse-
quently referred to as “sleep clinicians” in this document) should
discuss referral for upper airway or bariatric surgery evaluation
with adults with OSA. Surgical procedures included pharyngeal
soft tissue modifications, skeletal modification, and upper airway
stimulation, as described further in the accompanying systematic
review. Meta-analyses were performed on outcomes of interest,
when possible, for each PICO question. Patients unaccepting
of PAP were considered untreated for the purpose of these
analyses. Therefore, comparisons of surgery to no treatment
and/or assessment of efficacy before and after surgery to treat
OSA in adult patients were performed. The clinical practice rec-
ommendations were then developed according to the Grading of
Recommendations Assessment, Development and Evaluation
(GRADE) process.4 The TF assessed the following 4 components
to determine the direction and strength of a recommendation:
quality of evidence, balance of beneficial and harmful effects,
patient values and preferences, and resource use. Details of these
assessments can be found in the accompanying systematic
review.2 Additional information is provided in the form of
“Remarks” immediately following the recommendation state-
ments, when deemed necessary by the TF. Remarks are based
on the evidence evaluated during the systematic review and are
intended to provide context for the recommendations and to
guide clinicians in the implementation of the recommendations
in daily practice.
A draft of the guideline and systematic review was made avail-
able for public comment for a 4-week period on the AASM web-
site. The TF took into consideration all the comments received
and made decisions about whether to revise the draft based on
the comments. The revised guideline and systematic review
were submitted to the AASM Board of Directors for subsequent
approval.
RECOMMENDATIONS
The recommendations in this guideline define principles of prac-
tice that should meet the needs of most patients in most situations.
Each recommendation statement was assigned a strength
2500 December 1, 2021
 D Kent, J Stanley, RN Aurora, et al. Referral of adults with OSA for surgical consultation

(“Strong” or “Conditional”). A “Strong” recommendation is one
that clinicians should follow for almost all patients (ie, something
that might qualify as a quality measure). A “Conditional” recom-
mendation reflects a lower degree of certainty in the appropriate-
ness of the patient care strategy for all patients. It requires that the
clinician use clinical knowledge and expertise and strongly con-
siders the individual patient’s values and preferences to deter-
mine the best course of action. The ultimate judgment
regarding any specific care must be made by the treating clinician
and the patient, taking into consideration the individual circum-
stances of the patient, available treatment options, and resources.
The AASM expects this guideline to have an impact on profes-
sional behavior, patient outcomes, and—possibly—health care
costs. This clinical practice guideline reflects the state of knowl-
edge at the time of publication and will be reviewed and updated
as new information becomes available.
The following clinical practice recommendations are based
on a systematic review and evaluation of evidence using the
GRADE process. The implications of the strength of recommen-
dations for guideline users are summarized in Table 1. Remarks
are provided to guide clinicians in the implementation of these
recommendations.
Downloaded from jcsm.aasm.org by 64.124.192.2 on January 25, 2022. For personal use only. No other uses without permission.
studies showingclinically meaningful andbeneficial differences in
nearly all critical outcomes, and the benefits of discussing referral
over the harms of no treatment.
The TF investigated the use of upper airway surgery as rescue
therapy for adults with OSA who were intolerant or unaccepting
of positive airway pressure (PAP) to improve 1 or more of the fol-
lowing critical outcomes: excessive sleepiness, sleep quality,
quality of life (QOL), snoring, blood pressure (BP), apnea-
hypopnea index (AHI), and respiratory disturbance index
(RDI). The TF also considered the risks of perioperative death
and permanent dysphagia as critical outcomes for decision-
making. Meta-analyses demonstrated a clinically significant
reduction in excessive sleepiness, snoring, BP, and AHI/RDI,
and a clinically significant improvement in sleep-related and gen-
eral QOL. The results of the meta-analyses also demonstrated no
clinically significant risk of permanent dysphagia. The incidence
of perioperative death was not reported in the studies.
The overall quality of evidence was low due to imprecision and
risk of bias associated with observational studies. The potential
benefits of upper airway surgery as a rescue therapy include a
reduction in excessive sleepiness, snoring, BP, and AHI/RDI,
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
unaccepting of PAP
Recommendation 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).
Remarks: The recommendation to discuss referral is not
required to result in referral and does not preclude patient con-
sideration of other viable alternative treatment options (eg, man-
dibular advancement device, positional therapy, lifestyle
changes). The strong recommendation to discuss surgical refer-
ral with patients with a BMI < 40 kg/m2 is not a recommendation
Copyright 2022 American Academy of Sleep Medicine. All rights reserved.
considered appropriate for surgery by the treating surgeon and
may not be representative of all patients with OSA. The potential
harms of upper airway surgery include short-term discomfort that
is expected during postoperative recovery and is discussed during
the preoperative informed consent process between the surgeon
and patient. Additionally, potential persistent long-term side
effects have been reported including dysphagia, taste alteration,
mandibular paresthesia, perceived worsening of facial appear-
ance, aspiration, hemorrhage, and globus pharyngeus, but the
incidence of these is low. Surgery carries inherent risks, but based
on their combined clinical expertise and the substantial effects of
surgery on objective and subjective measures of disease, the TF
judged that the potential benefits of a discussion regarding refer-
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
deems it an appropriate management discussion point. For
patients within the BMI range of 35–40 kg/m2, discussion regard-
ing a referral to both sleep and bariatric surgeons (as per Recom-
mendation 2) to discuss management options is appropriate.
The TF made a strong recommendation in favor of discussing
surgical referral based on a large body of low-quality evidence
from 4 randomized controlled trials (RCTs) and 239 observational
that the balance of risks vs benefits for upper airway surgery is
highly dependent upon an individual patient’s OSA severity,
symptoms, medical comorbidities, and selected surgical therapy
but noted that a discussion of individualized risks and benefits
is a standard component of the preoperative informed consent
process. There are insufficient data to assess differences in
resource requirements for surgical referral vs no treatment.
Because acceptability of surgical interventions varies and there
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.

Journal of Clinical Sleep Medicine, Vol. 17, No. 12 2501 December 1, 2021
 D Kent, J Stanley, RN Aurora, et al.
clinical expertise the TF judged that most patients would gener-
ally be accepting of a discussion regarding referral. The choice
to pursue referral is expected to vary between patients based on
personal values, beliefs, and expectations for recovery time or
pain with surgery.
Surgical treatment of patients with obesity with
bariatric surgery
Recommendation 2: We recommend that clinicians discuss
referral to a bariatric surgeon with adults with OSA and obe-
sity (class II/III, BMI ≥ 35) who are intolerant or unaccepting
of PAP as part of a patient-oriented discussion of alternative
treatment options (STRONG).
Remarks: The recommendation to discuss referral is not
required to result in referral and does not preclude patient con-
sideration of medical weight loss strategies or other viable alter-
native treatment options for OSA. For patients within the BMI
range of 35–40 kg/m2, discussion regarding a referral to both
sleep and bariatric surgeons (as per Recommendations 1 and
3) to discuss management options is appropriate. The strong rec-
ommendation to discuss surgical referral with patients with OSA,
obesity, and PAP intolerance or unacceptance is not a recommen-
Downloaded from jcsm.aasm.org by 64.124.192.2 on January 25, 2022. For personal use only. No other uses without permission.
dation against (and does not preclude) discussion of surgical
referral with patients with OSA, obesity, and adequate PAP use
if the health care provider deems it an appropriate management
discussion point. Other organizations, such as the National
Heart, Lung, and Blood Institute, recommend consideration of
bariatric surgery for individuals suffering from obesity (class
II/III, BMI ≥ 35 kg/m2) and OSA, regardless of PAP adherence
status.5
The TF made a strong recommendation in favor of bariatric sur-
gery referral based on moderate-quality evidence from 2 RCTs
and 28 observational studies that showed clinically meaningful
improvements in several critical outcomes, and the benefits of
discussing referral over the harms of no treatment.
The TF investigated the use of bariatric surgery to improve 1 or
Copyright 2022 American Academy of Sleep Medicine. All rights reserved.
more of the following critical outcomes: BP, QOL, sleep quality,
OSA severity, and excessive sleepiness. The TF also considered
the risk of perioperative death as a critical outcome for decision-
making, although the risk of other serious persistent adverse
events and motor vehicle accidents was also reviewed. The TF
identified 2 RCTs and 28 pre- vs postsurgical treatment observa-
tional studies comparing the use of bariatric surgery vs no
treatment that reported on 1 or more of the critical outcomes.
Meta-analyses demonstrated a clinically significant improve-
ment in all critical outcomes. None of the studies reported on
the risk of perioperative death and motor vehicle accidents.
The overall quality of evidence was moderate due to large
effect sizes in the observational studies and due to imprecision
in the RCTs. The benefits of bariatric surgery in patients with obe-
sity and OSA include a reduction in AHI/RDI, BP, oxygen desa-
turation index (ODI), excessive sleepiness, BMI, snoring, and
optimal PAP level, and an increase in the minimum oxygen satu-
ration during sleep (LSAT). Benefits demonstrated in literature
are limited to patients considered appropriate for bariatric surgery
by the treating surgeon and may not be representative of all
Journal of Clinical Sleep Medicine, Vol. 17, No. 12
Referral of adults with OSA for surgical consultation
patients with obesity and OSA. While the benefits of bariatric sur-
gery are clinically significant, the surgeon needs to consider fac-
tors that would make a patient at higher risk for surgical
intervention, which are not captured by this analysis. Selection
bias may be present in the observed outcomes as adherence
with lifestyle changes is required of patients undergoing bariatric
surgery. It is difficult to determine whether the effects of bariatric
surgery on BP and the Epworth Sleepiness Scale (ESS) are
directly attributed to weight loss from surgery or the lowering
of AHI. Potential harms of bariatric surgery include short-term
discomfort that is expected during postoperative recovery and
is discussed during the preoperative informed consent process
between the surgeon and patient. Additionally, iron malabsorp-
tion, gastric ulcer, vitamin deficiency, bowel obstruction or
leak, gastrointestinal reflux disorder, and gastric band slippage
have been reported but the incidence of these is low. Bariatric sur-
gery carries inherent risks but based on their combined clinical
expertise and the substantial effects of bariatric surgery on objec-
tive and subjective measures of disease, the TF judged that the
potential benefits of a discussion regarding referral to a bariatric
surgeon with patients who are intolerant or unaccepting of PAP
therapy outweigh the potential harms of untreated OSA. The
TF observed that the balance of risks vs benefits for bariatric sur-
gery is highly dependent upon an individual patient’s OSA sever-
ity, symptoms, medical comorbidities, and selected surgical
therapy but noted that a discussion of individualized risks and
benefits is a standard component of the preoperative informed
consent process. There is insufficient evidence in the literature
to compare the costs of bariatric surgery to nutritional care or
untreated OSA. Because acceptability of surgical interventions
varies and there is little harm in discussing referral, based on their
combined clinical expertise the TF judged that most patients
would generally be accepting of a discussion regarding referral.
The choice to pursue referral is expected to vary between patients
based on personal values, beliefs, and expectations for recovery
time or pain with surgery.
Surgical treatment of patients to facilitate PAP use
Recommendation 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).
Remarks: Available data suggest that upper airway surgery has
a moderate effect in reducing minimum therapeutic PAP level and
increasing PAP adherence. The decision to offer referral should be
based onthe clinician’s judgmentofa patient’s currentPAP adher-
ence and tolerance as well as the patient’s treatment preferences.
Low degrees ofnonadherence orminimal side effects may preclude
consideration of a referral. Referral may be informed by the pres-
ence of other surgically treatable conditions that contribute to
upper airway obstruction(eg, persistentnasal obstruction, chronic
tonsillitis, malocclusion). For patients within the BMI range of
35–40kg/m2, discussionregardinga referraltobothsleep and bar-
iatricsurgeons (as per Recommendation 2) todiscuss management
options may be appropriate. The conditional recommendation to
2502 December 1, 2021
 D Kent, J Stanley, RN Aurora, et al.
discuss surgical referral with patients with a BMI < 40 kg/m2 is not
a recommendation against (and does not preclude) discussion
of surgical referral with patients with a BMI ≥ 40 kg/m2 if the
health care provider deems it an appropriate management discus-
sion point, especially as some surgical therapies that reduce
minimum therapeutic PAP level (eg, nasal surgery) are not antic-
ipated to be impacted by BMI.
The TF made a conditional recommendation in favor of surgical
referral based on very low-quality evidence from 7 observational
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
that likely vary depending on the patient’s degree of use.
The TF investigated the use of surgery as an adjunctive proce-
dure to facilitate the use of PAP by improving 1 or more of the fol-
lowing critical outcomes: optimal PAP level, excessive
sleepiness, sleep quality, PAP adherence, snoring, and sleep-
related QOL. The TF also considered the risks of perioperative
death and permanent dysphagia as critical outcomes for
decision-making. The TF identified 7 observational studies com-
paring pre- vs postsurgical treatment comparing 1 or more of the
critical outcomes. Meta-analyses of data extracted from these
studies were used to determine whether changes in these
Downloaded from jcsm.aasm.org by 64.124.192.2 on January 25, 2022. For personal use only. No other uses without permission.
outcomes were clinically significant. The results of the meta-
analyses demonstrated a clinically significant, moderate reduc-
tion in optimal PAP level and a clinically significant, moderate
improvement in PAP adherence with surgery. The incidence of
perioperative death and permanent dysphagia was not reported
in these studies. None of these studies reported on either QOL
or snoring.
The overall quality of evidence was very low due to impreci-
sion and risk of bias associated with observational studies. The
potential benefits of upper airway surgery as an adjunctive proce-
dure to facilitate effective PAP therapy include a reduction in
optimal PAP level, excessive sleepiness, and AHI/RDI, as well
as an increase in PAP adherence and lowest oxygen saturation
(LSAT). Benefits demonstrated in the literature are limited to
Copyright 2022 American Academy of Sleep Medicine. All rights reserved.
patients considered appropriate for surgery by the treating sur-
geon and may not be representative of all patients with PAP-
related side effects or inadequate use. The potential harms of
upper airway surgery as an adjunctive procedure include short-
term discomfort that is expected during postoperative recovery
and is discussed during the preoperative informed consent pro-
cess between the surgeon and patient. Surgery carries inherent
risks but based on their combined clinical experience and the
moderate effects of surgery on PAP pressure requirements and
adherence, the TF judged that the potential benefits of a discus-
sion regarding referral to a sleep surgeon for consideration of sur-
gery as an adjunctive procedure to facilitate PAP use may, in some
patients, outweigh the potential harms of inadequate PAP-related
side effects and adherence depending on their severity. If referral
is discussed, the TF observed that the balance of risks vs benefits
for upper airway surgery is highly dependent upon an individual
patient’s OSA severity, symptoms, medical comorbidities, and
selected surgical therapy but noted that a discussion of individu-
alized risks and benefits is a standard component of the preoper-
ative informed consent process. There are insufficient data to
Journal of Clinical Sleep Medicine, Vol. 17, No. 12
Referral of adults with OSA for surgical consultation
assess differences in resource requirements for surgical referral
vs inadequate PAP use. Because acceptability of surgical inter-
ventions varies and there is little harm in offering referral, based
on their combined clinical expertise the TF judged that most
patients would generally be accepting of a discussion regarding
referral but that its clinical utility may be more limited in patients
who are partially PAP adherent as opposed to those who are
completely untreated. The choice to pursue referral is expected
to vary between patients based on personal values, beliefs, and
expectations for recovery time or pain with surgery.
Surgical treatment as initial therapy in patients with a
major upper airway anatomical abnormality
Recommendation 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 refer-
ral for upper airway surgery (CONDITIONAL).
Remarks: Major upper airway anatomic abnormalities con-
sidered by the task force included tonsillar hypertrophy and max-
illomandibular abnormalities. While data suggest a clinically
significant benefit from surgical intervention in these popula-
tions, PAP should be recommended as initial treatment as it car-
ries minimal risk relative to surgery. The decision to discuss
referral for initial surgical therapy should be based on the clini-
cian’s judgment of the patient’s medical history as consideration
of initial surgical intervention may be justified in the setting of
other surgical indications affecting upper airway patency
(eg, chronic tonsillitis, malocclusion, abnormal lesion, or
growth). The conditional recommendation does not preclude dis-
cussion of surgical referral prior to the initial PAP trial if the
health care provider deems it an appropriate management dis-
cussion point. Furthermore, this recommendation is for the initial
treatment of OSA and does not address management of patients
who have previously trialed PAP, as detailed in Recommenda-
tions 1–3.
The TF made a conditional recommendation against surgical
referral as initial treatment for OSA based on low-quality evi-
dence from 2 RCTs and 15 observational studies, the balance of
benefits to harms favoring PAP as an initial treatment over sur-
gery, and the benefits of discussing referral over the harms of
PAP as an initial OSA therapy trial.
The TF investigated the use of surgery to improve 1 or more of
the following critical outcomes: AHI/RDI, excessive sleepiness,
sleep quality, LSAT, sleep-related QOL, snoring, and oxygen
desaturation. The TF also considered the risks of perioperative
death and permanent dysphagia as critical outcomes for
decision-making, although the risk of other serious persistent
adverse events and motor vehicle accidents was also reviewed.
The TF identified 2 RCTs and 15 pre- vs postsurgical treatment
observational studies comparing the use of surgery vs no treat-
ment that reported on 1 or more of the critical outcomes. Studies
including patients with prior PAP treatment were not excluded
from analysis as prior PAP exposure was not anticipated to rea-
sonably affect response to anatomy-altering surgery. Meta-
analyses demonstrated a clinically significant reduction in AHI/
RDI, excessive sleepiness, snoring, and oxygen desaturation
2503 December 1, 2021
 D Kent, J Stanley, RN Aurora, et al.
index (ODI) and a clinically significant improvement in the
LSAT with surgery. There was no evidence to assess improve-
ment in sleep-related QOL. The results of the meta-analyses
also demonstrated no clinically significant risk of permanent dys-
phagia. The incidence of perioperative death was not reported in
the studies. None of the studies reported on the risk of motor vehi-
cle accidents.
The overall quality of evidence was low due to imprecision and
risk of bias associated with the observational studies. The poten-
tial benefits of upper airway surgery as an initial therapy include a
reduction in excessive sleepiness, snoring, systolic blood pres-
sure, AHI/RDI, and ODI and an increase in LSAT. Benefits dem-
onstrated in the literature are limited to patients with a major
anatomical obstruction considered appropriate for surgery by
the treating surgeon and may not be representative of all patients
with OSA with similar anatomic findings. The potential harms of
surgery include short-term discomfort that is expected during
postoperative recovery and is discussed during the preoperative
informed consent process. Additionally, potential persistent
long-term side effects have been reported including dysphagia,
taste alteration, mandibular paresthesia, aspiration, hemorrhage,
and globus pharyngeus, but the incidence of these is low. Given
that even low surgical risks are elevated as compared to the min-
imal risk of initial PAP therapy, the balance of benefits to harms
Downloaded from jcsm.aasm.org by 64.124.192.2 on January 25, 2022. For personal use only. No other uses without permission.
favors PAP therapy as initial treatment over discussion of referral
for surgical evaluation. Nevertheless, the presence of major ana-
tomical obstruction may tip the balance in favor of surgical refer-
ral discussion depending on a patient’s upper airway medical
history. Despite the low risk of surgical referral discussion, there
is no harm in an initial trial of PAP therapy if other surgical indi-
cations are not present. Given that the intent of discussion of sleep
surgery referral in this clinical scenario is consideration of upper
airway surgery prior to any PAP trial, based on their combined
clinical expertise, the TF judged that the potential benefits of sur-
gical referral discussion in patients with major anatomical
obstruction do not exceed the potential benefits of an initial
PAP trial for OSA in the absence of other medical conditions
affecting upper airway patency. Based on their combined clinical
Copyright 2022 American Academy of Sleep Medicine. All rights reserved.
expertise, the TF judged that most patients would generally be
accepting of a discussion regarding referral for surgical evalua-
tion as there is little harm in the act of offering. Patient acceptance
of surgical interventions will vary, and the clinical utility of refer-
ral may be more limited in patients who are partially PAP adher-
ent. The choice to pursue referral is expected to vary between
patients based on personal values, beliefs, and expectations for
recovery time or pain with surgery.
DISCUSSION
Positiveairwaypressure(PAP)isrecognizedasthemostefficacious
treatment for the majority of OSA outcomes if worn consistently,
but a growing body of literature confirms that a substantial portion
of patients do not accept or tolerate it as a treatment option.6–9 Poor
adherence to PAP therapy likely compromises patients’ ability to
derive all potential subjective and objective benefits. A variety of
alternatives to PAP for OSA treatment exist, including surgical
interventions. New diagnostic tools and improved surgical
Journal of Clinical Sleep Medicine, Vol. 17, No. 12
Referral of adults with OSA for surgical consultation
techniques have proliferated over the last 10–15 years as surgeons
have developed more effective and less morbid procedures better
tailored to the individual patient’s anatomy.
Surgical treatments for OSA demonstrate large reductions in
objective disease burden and patient-centered outcomes as com-
pared to no treatment. Patients who are intolerant or unaccepting
of PAP therapy should be informed that surgical management is
one of several viable alternative treatment options. The recommen-
dation to discuss referral does not preclude a patient-oriented dis-
cussion of other viable alternative treatment options (eg,
mandibular advancement device, positional therapy, behavioral
changes)that may yieldfavorable benefitover nofurther treatment.
The decision to undergo surgical treatment for OSA is a personal
one, and the risk-benefit ratio will vary given an individual’s
own values, personal preferences, anatomy, and medical history.
Health care providers are encouraged to consider these factors dur-
ing a discussion regarding referral, understanding that as the field
of surgery continues to rapidly evolve, the surgeon may ultimately
have the most current and comprehensive understanding of the evi-
dence surrounding a patient’s individualized surgical indications,
risks, and potential outcomes. A patient-tailored discussion of
appropriate surgical risks and benefits is a standard component
of the informed consent process conducted by the surgeon so that
a patient may make an informed decision. A discussion of the
short-term andlong-term sideeffects of surgery arepart of that con-
versation. A potential limitation regarding this management option
is access to a surgeon familiar with the variety of modern surgical
techniques for OSA.Sleep surgeons havea responsibility toremain
current on new discoveries underlying the pathophysiologic mech-
anisms of OSA, as these findings will likely inform an individual
patient’s surgical candidacy in the future. Close collaboration
with referring sleep medicine colleagues will help foster multidis-
ciplinary educational opportunities. Surgeons interested in treating
thispatientpopulationshouldhavean appropriateunderstandingof
sleep medicine and modern surgical techniques.
Upper airway surgery may have a moderate effect on decreas-
ing therapeutic PAP requirements (ie, optimal PAP level) and
increasing PAP adherence although this estimate is based on a
small number of uncontrolled observational studies. Considering
the very low risk of surgical referral discussion and the informed
consent process, clinicians should consider discussing referral to
a surgeon with patients struggling with PAP tolerance and adher-
ence who have not responded adequately to previously attempted
nonsurgical treatments.
Some patients are noted to have major anatomic obstruction on
initial evaluation, such as tonsillar hypertrophy or significant
maxillomandibular deficiencies. Despite the large effect size
seen with the appropriately indicated surgery, the high efficacy,
low cost, and minimal harm of PAP therapy justify an initial trial
prior to consideration of surgical referral. It is important to
remember that additional patient history (eg, chronic tonsillitis,
malocclusion) may justify discussion of a surgical referral prior
to an initial medical therapy trial. Patients with major anatomic
obstruction who refuse PAP therapy should discuss referral for
surgical evaluation with their health care provider.
Weight loss can have a substantial impact on OSA disease bur-
den in obese patients. Bariatric surgery is the most effective ther-
apy for weight loss in patients with class II or III obesity.
2504 December 1, 2021
 D Kent, J Stanley, RN Aurora, et al.
Discussion regarding bariatric surgery referral should be consid-
ered in this population, which may be considered in parallel with
medical weight loss options as well as other OSA treatments. Dur-
ing the consultation, the surgeon will discuss lifestyle changes
necessary to be successful with bariatric surgery. Ultimately,
patients will have to agree to major lifestyle changes to be suc-
cessful with bariatric surgery, and some are not ready for these
changes. Although not specifically included in this review, avail-
able data suggest bariatric surgery can reduce positive airway
pressure requirements and improve PAP adherence. Referral
may be limited by proximity to a bariatric surgery center, and
varying insurance coverages may impact patient access to this
treatment option. A growing evidence base from patients outside
the US with class I obesity and access to bariatric surgery suggests
significant potential health benefits in this population as well. The
potential for surgical weight loss benefits in patients with OSA
and body mass index less than 35 kg/m2 will require further eval-
uation in the coming years.
REFERENCES
1. Aurora RN, Casey KR, Kristo D, et al. American Academy of Sleep Medicine. Practice
parameters for the surgical modifications of the upper airway for obstructive sleep
Downloaded from jcsm.aasm.org by 64.124.192.2 on January 25, 2022. For personal use only. No other uses without permission.
apnea in adults. Sleep. 2010;33(10):1408–1413.
2. Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea
for surgical consultation: an American Academy of Sleep Medicine systematic
review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):
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
Medicine clinical practice guideline. J Clin Sleep Med. 2019;15(2):335–343.
4. Morgenthaler TI, Deriy L, Heald JL, Thomas SM. The evolution of the AASM clinical
practice guidelines: another step forward. J Clin Sleep Med. 2016;12(1):129–135.
5. National Institutes of Health; National Heart, Lung, and Blood Institute; North American
Association for the Study of Obesity. The Practical Guide: Identification, Evaluation, and
Treatment of Overweight and Obesity in Adults. NIH Publication No. 00-4084. https://
www.nhlbi.nih.gov/files/docs/guidelines/prctgd_c.pdf. Accessed August 17, 2021.
6. Cistulli PA, Armitstead J, Pepin JL, et al. Short-term CPAP adherence in
obstructive sleep apnea: a big data analysis using real world data. Sleep Med.
2019;59:114–116.
Copyright 2022 American Academy of Sleep Medicine. All rights reserved.
Journal of Clinical Sleep Medicine, Vol. 17, No. 12
Referral of adults with OSA for surgical consultation
7. Jacobsen AR, Eriksen F, Hansen RW, et al. Determinants for adherence to continuous
positive airway pressure therapy in obstructive sleep apnea. PLoS One. 2017;12(12):
e0189614.
8. Kohler M, Smith D, Tippett V, Stradling JR. Predictors of long-term compliance with
continuous positive airway pressure. Thorax. 2010;65(9):829–832.
9. Virk JS, Kotecha B. When continuous positive airway pressure (CPAP) fails. J Thorac
Dis. 2016;8(10):E1112–E1121.
ACKNOWLEDGMENTS
The task force acknowledges the early contributions of Edward Weaver, MD, MPH
(University of Washington Medical Center, Seattle, WA), who assisted with the
development of the PICO questions and project charter. The task force also thanks
Ofer Jacobowitz, MD, PhD (Icahn School of Medicine at Mount Sinai, New York, NY);
Eric J. Kezirian, MD, MPH (Keck School of Medicine of University of Southern
California, Los Angeles, CA); Reena Mehra, MD, MS (Cleveland Clinic, Cleveland,
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.
This guideline was endorsed by the American Society for Metabolic and Bariatric
Surgery and the Alliance of Sleep Apnea Partners. The American Academy of
Otolaryngology–Head and Neck Surgery affirmed the value of this guideline.
SUBMISSION & CORRESPONDENCE INFORMATION
Submitted for publication August 3, 2021
Submitted in final revised August 3, 2021
Accepted for publication August 3, 2021
Address correspondence to: David Kent, MD, Department of Otolaryngology, Vanderbilt
University, 3601 21st Avenue South, Nashville, TN 37232;
Email: davidkentmd@gmail.com
DISCLOSURE STATEMENT
The development of this paper was funded by the American Academy of Sleep
Medicine (AASM). Dr. David Kent is listed as an inventor on U.S. and international
patent applications regarding surgical treatments for OSA owned and licensed by
Vanderbilt University (VU) to Nyxoah SA. Dr. Kent receives a portion of any licensing
revenues as per standard VU technology transfer policy. The licensed treatment
methodologies do not currently exist in prototype or commercial form and are not
represented in the surgical literature reviewed by the TF. The licensing agreement was
completed in early 2021, after completion of the initial clinical practice guideline,
supporting systematic review, and public comment period. Mr. Harrod is employed by
the AASM. The other authors report no conflicts of interest.
2505 December 1, 2021
 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.

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 Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea
A
dult obstructive sleep apnea (OSA) is associated with
numerous adverse effects if left untreated, including
daytime sleepiness, reduced quality of life, increased
cardiovascular morbidity and mortality, and an increased risk
of motor vehicle crashes. 1-3 A narrow or unstable upper
airway4 predisposes to episodes of complete or partial air-
flow reduction (ie, obstructive apnea or hypopnea) during
sleep when pharyngeal dilator muscle tone falls. Continuous
positive airway pressure (CPAP) delivered by mask, or jaw
advancement with an oral appliance, can alleviate obstruc-
tion; however, many patients either refuse these therapies,
use them inconsistently, or (as in the case of oral appliances)
achieve suboptimal efficacy, leaving at least 50% of patients
without effective treatment5,6 and exposed to the risk of seri-
ous long-term morbidity. Surgical treatments aim to enlarge
and stabilize the upper airway and may provide an option for
patients in whom conventional medical treatment had
failed.7 However, to date, there have been few randomized
trials evaluating the benefits and complications of these sur-
gical procedures compared with controls,8-11 and most have
tested surgical treatment at a single level of the upper airway
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
relieve both retropalatal and retrolingual obstruction in adult
patients who had moderate or severe symptomatic OSA for
whom conventional device treatment had failed. The pri-
mary hypothesis was that surgery would be more effective than
ongoing medical management in improving OSA, as mea-
sured by a decrease in the frequency of sleep apneas and hy-
popneas and a reduction in subjective daytime sleepiness.
Methods
Ethical Approval and Informed Consent
Each of the participating sites had human research ethics ap-
proval to conduct the study. An independent data and safety
monitoring board regularly reviewed data on serious and non-
serious adverse events and study quality. Written informed
consent was obtained from each participant.
Study Design and Patients
This was a multicenter, parallel-group, open-label, random-
ized clinical trial of upper airway surgery vs ongoing medical
management conducted across 6 Australian academic cen-
ters. The study reporting conforms to CONSORT guidelines for
randomized trials. The full protocol and statistical analysis plan
for this trial are available in Supplement 1. The rationale and
design of the study has been published previously.12
Eligible adults were aged 18 to 70 years with moderate or
severe OSA (defined as apnea-hypopnea index [AHI] of 15-30
and >30 events/h of sleep), body mass index less than 38, and
Epworth Sleepiness Scale (ESS) greater than 8 (range, 0-24;
higher scores indicate greater sleepiness) in whom medically
supervised attempts to use CPAP and, when deemed appro-
priate, a mandibular advancement device failed or were re-
fused. Patients were excluded if they had significant medical
jama.com
© 2020 American Medical Association. All rights reserved.
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Preliminary Communication Research
Key Points
Question Is multilevel airway surgery effective in adults with
moderate or severe obstructive sleep apnea (OSA) who cannot
tolerate or adhere to device use?
Findings In this randomized clinical trial of 102 adults, modified
uvulopalatopharyngoplasty and radiofrequency in saline tongue
reduction, compared with ongoing medical management,
significantly improved the apnea-hypopnea index (mean
baseline-adjusted between-group difference, −17.6 events per
hour of sleep) and patient-reported sleepiness (mean
baseline-adjusted between-group difference in Epworth
Sleepiness Scale, −6.7; range, 0-24; higher score indicates greater
sleepiness) at 6 months.
Meaning In this preliminary study of adults with moderate or
severe OSA who failed conventional treatment, combined palatal
and tongue surgery improved patient-reported sleepiness and
polysomnographic measures of OSA severity at 6 months,
although further research is needed to confirm these findings in
additional populations and to evaluate the safety, clinical utility,
and long-term efficacy of multilevel upper airway surgery for
treatment of individuals with OSA.
or psychiatric comorbidities, were judged to be a high anes-
thetic risk, were pregnant, or had specific anatomical contra-
indications to the intended surgery (eg, severe palatal scar-
ring from previous surgery or severe retrognathia). A full
description of the inclusion and exclusion criteria is provided
in eTable 1 in Supplement 2.
After eligibility was confirmed, participants were ran-
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-
location ratio) was used to ensure balance between variables
that had the potential to affect outcomes, namely, study site,
sex, age (<50, ≥50 years), AHI (<50, ≥50 events/h), and body
mass index (<28, ≥28). Enrollment began in August 2014, but,
because of slow recruitment, the protocol was amended in
January 2016 after reaching 30% of the recruitment target (31
of 102 planned participants) to relax the body mass index ex-
clusion threshold from greater than 35 to greater than 38 and
lower the AHI inclusion requirement from greater than 20 to
greater than 15 events per hour.
Interventions
The surgery intervention (eFigure in Supplement 2) con-
sisted of a modified uvulopalatopharyngoplasty to widen and
stabilize the velopharynx and 7 to 9 submucosal insertions of
a radiofrequency-in-saline wand to reduce tongue volume as
previously described.14 A training workshop was conducted
to standardize the surgical techniques among the 7 participat-
ing surgeons.12 Ongoing medical management consisted of a
range of evidenced-based treatments as appropriate (eg, weight
loss, alcohol reduction, sleep posture modification, medical
management of nasal obstruction) and assistance with retrial
of CPAP or mandibular advancement device therapies if par-
ticipants were willing.
(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
The follow-up assessment was scheduled for 6 months after
the surgical intervention for the surgery group and for 6 months
after the date of baseline assessments for the ongoing medi-
cal management group. All participants were assessed by a phy-
sician certified in sleep medicine at baseline and at 1, 3, and 6
months. Participants in the surgery group were also assessed
by a surgeon before surgery; at the time of surgery; and 1, 3,
and 6 months after surgery (eTable 2 in Supplement 2). Vali-
dated questionnaires measured patient- and partner-
reported outcomes at baseline and each follow-up. Demo-
graphic information, medical information, OSA treatments
used, and body mass index were measured for all enrolled par-
ticipants at baseline and at each follow-up visit. Information
on race was collected because severity of OSA can vary by race,
and it was defined by participants using an open-ended ques-
tionnaire. Friedman stage was determined at baseline by di-
rect visualization of tongue position, tonsil size, and measure-
ment of body mass index. Stages I through IV denote the
presence of anatomical features previously considered to range
from the most to least favorable for upper airway soft tissue
surgery: stage I indicates low tongue position with moderate
or severe tonsil enlargement; stage II, low tongue/no or mi-
nor tonsil enlargement or high tongue position/moderate or
severe tonsil enlargement; stage III, high tongue position/no
or minor tonsil enlargement; and stage IV, body mass index
greater than 40 or skeletal deformities (eg, micrognathia or
midface hypoplasia).15 The exclusion criterion for this study
precluded the recruitment of patients with Friedman stage IV.
All adverse events and postsurgery symptoms, regardless of
their severity, were systematically recorded at each of the
follow-up appointments.12 Serious adverse events were based
on the guidelines adopted by the International Conference on
Harmonization of Good Clinical Practice.16
Polysomnography, multiple sleep latency tests, and blood
pressure measurements occurred at baseline and 6 months.
The sleep tests were scored according to the American Acad-
emy of Sleep Medicine 2007 manual17 at a central sleep labo-
ratory (Adelaide Institute for Sleep Health) by 2 experienced
sleep technicians who were blinded to patient treatment al-
location. For the AHI, the alternate criteria was used with hy-
popnea defined as 50% reduction in airflow for at least 10 sec-
onds and associated with either a 3% oxyhemoglobin
desaturation or a cortical arousal.17 The multiple sleep la-
tency test consisted of 5 daytime 20-minute sleep opportuni-
ties spaced 2 hours apart from which mean sleep latency was
calculated as the mean time to sleep onset after lights out.18
Office and 24-hour ambulatory blood pressure measure-
ments were obtained at baseline and again at 6 months. It was
not possible to blind the research staff assisting with the other
evaluations. Further details on patient assessments are pro-
vided in Supplement 2.
Study Outcomes
The primary study outcomes were the baseline-adjusted dif-
ferences between groups in the AHI and ESS19 at 6 months. The
AHI reports the number of apnea and hypopnea events per hour
of sleep, with 0 to 5 signifying no OSA; 5 to 14, mild OSA;
1170 JAMA September 22/29, 2020 Volume 324, Number 12 (Reprinted)
© 2020 American Medical Association. All rights reserved.
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15-30, moderate OSA; and greater than 30, severe OSA (a change
of ≥15 is considered the minimal clinically important
difference).2 The ESS evaluates patient self-reported sleepi-
ness (range, 0-24; higher scores indicate greater severity; >10
signifies pathological sleepiness; change of 2 indicates the mini-
mal clinically important difference).20
Secondary outcomes included the following polysomnog-
raphy measures of OSA severity and sleep quality: the per-
centage of participants with AHI less than 10, the apnea in-
dex, 3% and 4% oxygen desaturation indices, the lowest oxygen
saturation in sleep, percentage of sleep time with oxygen satu-
ration <90%, AHI and lowest oxygen saturation in supine and
nonsupine sleep positions, arousal index, and percentages of
total sleep time spent in sleep stages nonrapid eye movement
stage 1 (N1) through N3 and in rapid eye movement (REM) sleep
(mean available age-appropriate normal values: lowest oxy-
gen saturation, 90.5% [95% CI, 89.3%-91.7%]; arousal index,
12.5 [95% CI, 10.7-14.2]; N1 sleep, 8.0% of sleep time [95% CI,
6.9%-9.2%]; N2 sleep, 52.2% of sleep time [95% CI, 50.6%-
53.8%]; N3 sleep, 20.4% of sleep time [95% CI, 18.5%-22.2%];
REM sleep, 19.3% of sleep time [95% CI, 18.2%-20.3%])21; there
are no agreed minimal clinically important difference values
for these parameters. Other secondary outcomes were objec-
tive daytime sleepiness, measured with the multiple sleep la-
tency test and expressed as mean sleep latency in minutes (val-
ues below 10 minutes signify an increased propensity to fall
asleep; the minimal clinically important difference is 1
minute2); partner-reported patient snoring, measured with the
Snoring Severity Scale22 (range, 0-9; higher scores indicate
more intense snoring; no agreed minimal clinically impor-
tant difference); sleep-specific quality of life, measured with
the Functional Outcomes of Sleep Questionnaire-3023 (range,
5-20; higher scores indicate better functional status; ≥17.9 is
considered normal; a score change of 1 is considered to be the
minimal clinically important difference24); generic health-
related quality of life25 and self-rated health status,26 mea-
sured with the EuroQol Group 5-dimension 5-level (EQ-5D-
5L) instrument (utility index range, −0.594 to 125; higher scores
indicate better quality of life; score change ranging from 0.03-
0.52 are considered the minimal clinically important differ-
ences in other diseases there is no minimal clinically impor-
tant difference established for OSA27]) and EQ visual analogue
scale (range, 0 [worst possible health] to 100 [best possible
health]; score changes ranging from 3.5-10.1 considered to be
the minimal clinically important differences in other
diseases28,29); the Glasgow Benefit Inventory,30 which was
completed by participants randomized to the surgery group
6 months after the surgical procedure (change in quality of life
following surgery is graded from −100 [poorest outcome] to
100 [best outcome], with 0 indicating no change; no reported
minimal clinically important difference); and office and am-
bulatory 24-hour, daytime, and nighttime blood pressure (mini-
mal clinically important difference for 24-hour ambulatory
blood pressure is 1 mm Hg2). Some other outcomes were col-
lected to provide mechanistic insights (eg, anthropometric
measures, adherence to other OSA therapies). Data on cost,
imaging, and nasendoscopic findings were collected but are
not reported in this article. Serious adverse event rates were
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 Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea
scored as the percentage of patients with 1 or more serious ad-
verse events.
Statistical Analysis
Based on data from a preliminary study,12,14 a sample size of
51 participants per group was estimated to provide at least 80%
power to detect superior reductions in AHI and ESS with sur-
gery compared with medical management as demonstrated by
the lower limit of the 95% CI for the difference in mean val-
ues at 6 months being at least 20 events per hour for the AHI
and 3 units for the ESS.12 These differences are greater than the
minimal clinically important differences of 15 events per hour
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
The sample size was based on the ESS primary outcome be-
cause it required a larger sample than the AHI primary out-
come. The a priori sufficiently important31 superiority margin
was set to 3 in ESS change between the groups at 6 months, and
an SD of 5 was estimated based on the preliminary study.12,14
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
provided an adjustment in case of a nonnormal distribution,
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.
Descriptive data are presented using mean and SD for nor-
mally distributed continuous data and frequency and percent-
age for categorical data. Within-group changes and between-
group differences are presented with 95% CIs. Participants were
analyzed according to their randomization group. All partici-
pants with data at baseline were included in the analysis, with
missing data assumed to be missing at random and any poten-
tial bias in estimated effects accounted for by the use of mixed-
effects models. For all continuous outcome variables, the ef-
fect of treatment was assessed on the basis of the difference in
the 6-month follow-up values between groups after adjust-
ment for baseline values. Differences were obtained using lin-
ear mixed-effects models with a Poisson link distribution func-
tion used for those variables for which the outcome could be
interpreted as a count and for which the distribution of either
the level 1 or level 2 residuals were nonnormally distributed. The
relevant outcome was the dependent variable and fixed-
effects terms for the intervention group, visit (baseline or 6
months), and an interaction between group and visit, which was
interpreted as the intervention effect. The participant ID was
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
were analyzed using Stata, version 15.0 (StataCorp).
Effect estimates are reported as mean (95% CI). Hypoth-
esis testing was 2-sided and P < .05 was considered statisti-
cally significant. Corrections for multiple comparisons were
not applied to the 2 primary outcomes because they were con-
sidered independent and fall into distinct families of equally
important outcomes. Because of the potential for type I error
due to multiple comparisons, findings for analyses of second-
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Preliminary Communication Research
Figure 1. Recruitment, Randomization, and Flow of Participants
in a Study of the Effect of Upper Airway Surgery vs Ongoing Medical
Management on Patients With Obstructive Sleep Apnea
612 Patients assessed for eligibility
510 Excluded
449 Did not meet inclusion
criteria
54 Refused to participate
7 Trial was full
102 Randomized
51 Randomized to the surgery group 51 Randomized to the ongoing
50 Underwent surgery medical management group
1 Withdrew consent before
surgery
2 Lost to follow-up 8 Lost to follow-up
1 Withdrew consent 4 Withdrew consent
1 Lost contact 4 Lost contact
50 Included in analysis 49 Included in analysis
1 Withdrew before data collection 2 Withdrew before data collection
and was excluded from analysis and were excluded from analysis
ary end points should be interpreted as exploratory. Al-
though it was not prespecified in the trial protocol or statisti-
cal analysis plan (Supplement 1), it was considered important
that both primary outcomes (ie, nighttime respiratory distur-
bance [AHI] and self-reported sleepiness [ESS]) would need to
decrease significantly to demonstrate clinical efficacy.
Post hoc sensitivity analyses were conducted to explore
whether there was significant heterogeneity of treatment ef-
fect among the 7 surgeons by including a group × surgeon in-
teraction term in the models for the 2 primary outcomes (AHI
and ESS). Five of the 6 sites had only 1 assessing surgeon and
the other site had 2 assessing surgeons. To assess whether there
was any clustering effect of participants within surgeon, an ad-
ditional random intercept for surgeon was used in the mixed-
effects models. In addition, because inclusion criteria were al-
tered when enrollment was approximately 30% complete to
change AHI from greater than 20 to greater than 15 and body
mass index from less than or equal to 35 to less than or equal
to 38, a post hoc sensitivity analysis was conducted to deter-
mine whether results were different among participants who
met the original inclusion criteria for the study.
Results
Study Overview
A total of 612 participants were screened for eligibility (Figure 1):
102 met the eligibility criteria and were enrolled in the study
between November 2014 and October 2017, with the last
follow-up visit conducted in August 2018. Eleven partici-
pants did not complete the study (3 in the surgery group
and 8 in the ongoing medical management group). For the
2 primary outcomes, there was missing data for the ESS for
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 Research Preliminary Communication Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea

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%

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 Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea Preliminary Communication Research

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,
with the black line in the middle illustrating the median. The dashed line
signifies the mean. Whiskers extend to the upper and lower adjacent values, the
location of the furthest point within a distance of 1.5 interquartile ranges from
the first and third quartiles. The parallel line plot contains 1 vertical line for each
patient which extends from their baseline value to their 6-month value.40
Descending lines indicate an improvement in symptoms. Baseline values are
placed in ascending order for the surgery group and descending order for the
ongoing medical management group. A, The AHI indicates the number of apnea
and hypopnea events per hour of sleep (0-5 is classified as normal; 5-14, mild
OSA; 15-30, moderate OSA; >30, severe OSA; a change of at least 15 is
considered clinically meaningful and can move a patient 2 levels from severe to
mild with established benefit for health2). B, The ESS19 evaluates sleepiness
(range, 0-24; higher scores indicate greater severity; score >10 signifies
pathological sleepiness; a change of 2 is the minimally important clinical
difference20).

CI, 2.5-4.4]; P < .001), and self-rated general health status
(EQ visual analog scale score: 10.5 [95% CI, 5.6-15.4];
P < .001), but were not statistically significantly different for
general health-related quality of life (EQ-5D-5L score: 0.06
[95% CI, 0.00-0.12]; P = .054) (Table 2). Participants in the
surgery group identified specific health benefits from the
surgical procedures (mean [SD] Glasgow Benefit Inventory,
32.1 [22.8]) (eTable 7 in Supplement 2). Mean blood pressure
values were normal at baseline and showed no significant
between-group difference at 6 months (in-office systolic
blood pressure: −2.5 [95% CI, −7.1 to 2.2]; P = .30; in-office
diastolic blood pressure: −3.9 [95% CI, −8.1 to 0.3]; P = .07)
(Table 2 and eTable 7 in Supplement 2).
Very few participants attempted to use CPAP (n = 7) or a
mandibular advancement device (n = 1) during the trial, and
there was no significant weight loss in either study group
(between-group difference, −1.2 kg [95% CI, −2.8 to 0.4]; P = .14)
or change in health behaviors (eTable 7 in Supplement 2).
Post Hoc Sensitivity Analyses
There was no significant difference in treatment effect among
surgeons for the AHI (χ 25 = 5.66; P = .34) or the ESS (χ 25 = 4.51;
P = .48). There was also no significant difference in the treatment
effects after incorporating a random intercept for surgeons into
each model or when using data only for participants who met
the original inclusion criteria (eTable 8 in Supplement 2).

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 Research Preliminary Communication Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea

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)

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 Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea Preliminary Communication Research

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

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 Research Preliminary Communication Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea

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

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 Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea Preliminary Communication Research

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

reduce, not eliminate, obstructive breathing events. The
reduction in AHI in the surgery group was substantial and
similar to the net effect of CPAP treatment35 and the decrease
in AHI achieved with oral appliances36 and hypoglossal nerve
stimulation.37 Most importantly, this study has shown sub-
stantial improvements in patient-centered outcomes in
patients unable to use conventional OSA treatment. The sur-
gery does not preclude reintroducing CPAP or other therapies
later, if required. The perception that CPAP treatment is prob-
lematic after uvulopalatopharyngoplasty arises from a single
early report of more mouth leaks with nasal CPAP after exci-
sional uvulopalatopharyngoplasty.38 However, the modified
uvulopalatopharyngoplasty used in this study reduces retro-
palatal obstruction while preserving the palate and velopha-
ryngeal sphincter function such that problems with reappli-
cation of CPAP are rare.39
The strengths of this study include the randomized clini-
cal trial design, sufficient sample size and duration of fol-
low-up to ascertain treatment effects independent of short-
term postoperative discomfort and physiological disturbance,
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
technique is similar to other contemporary, widely used uvu-
lopalatopharyngoplasties that open the lateral palate,8,9 and
radiofrequency is a common otolaryngologic intervention. The
findings may have broader clinical relevance because the sur-
gical exclusion criteria were relatively limited and most ana-
tomical subtypes were included, as 84% of patients meeting
general screening and medical criteria were surgically eli-
gible and enrolled in the trial.
This study has several limitations. First, although the study was
adequately powered to establish efficacy, generalizability from
any randomized clinical trial is inherently limited by numbers
of patients and surgeons, and this study did not meet the suf-
ficiently important difference for AHI (but did surpass the mini-
mal clinically important difference). Thus, further studies will
be needed to establish the long-term effectiveness, safety, and
cost-effectiveness of this surgical treatment for OSA. Second,
this study included a select population that excluded patients
with severe obesity (ie, body mass index of 38 or greater), pa-
tients older than 70 years, and patients with retrognathia and
significant comorbidities; women were underrepresented in the
trial. Therefore, the results may not generalize to the larger OSA
population. Third, because the surgical intervention caused pain
and anatomical changes, it was not possible to blind patients
and some of the clinical assessors to treatment group random-
ization. Hence, some of the observed effects, such as self-
reported sleepiness, may have been influenced by participant
expectancy, although this bias is less likely to have affected the
blinded objective measures of OSA (polysomnography).
Conclusions
In this preliminary study of adults with moderate or severe OSA
who had failed conventional treatment, combined palatal and
tongue surgery, compared with ongoing 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 under-
stand clinical utility, long-term efficacy, and safety of multi-
level upper airway surgery for treatment of patients with OSA.

ARTICLE INFORMATION
Accepted for Publication: July 15, 2020.
Published Online: September 4, 2020.
doi:10.1001/jama.2020.14265
Author Affiliations: Illawarra Shoalhaven Local
Health District, Wollongong, NSW, Australia
(MacKay, Jones); University of Wollongong, NSW,
Australia (MacKay, Jones); Illawarra ENT Head and
Neck Clinic, Wollongong, NSW, Australia (MacKay);
Southern ENT & Adelaide Sinus Centre, Flinders
Private Hospital, Adelaide, SA, Australia (Carney);
College of Medicine and Public Health, Flinders
University, Adelaide, SA, Australia (Carney, Ooi,
Woods); Adelaide Institute for Sleep Health, College
of Medicine and Public Health, Flinders University,
Adelaide, SA, Australia (Catcheside, Chai-Coetzer,
Pinczel, McEvoy); Respiratory and Sleep Service,
Southern Adelaide Local Health Network, Adelaide,
SA, Australia (Chai-Coetzer, McEvoy); Department
of Thoracic Medicine, Royal Adelaide Hospital,
Adelaide, SA, Australia (Chia, Yeo); Charles Perkins
Centre, Faculty for Medicine and Health, University
of Sydney, NSW, Australia (Cistulli); Department of
Respiratory and Sleep Medicine, Royal North Shore
Hospital, Sydney, NSW, Australia (Cistulli); Ear Nose
and Throat Department, Royal Adelaide Hospital,
Adelaide, SA, Australia (Hodge); Illawarra Sleep
Medicine Centre, Wollongong, NSW, Australia
(Jones); Health Economics Unit, College of
Medicine and Public Health, Flinders University,
Adelaide, SA, Australia (Kaambwa); Hollywood
Medical Centre, Perth, WA, Australia (Lewis);
Department of Otolaryngology, Head & Neck
Surgery, Royal Perth Hospital, Perth, WA, Australia
(Lewis); Department of Otolaryngology, Head and
Neck Surgery, Flinders Medical Centre, Adelaide,
SA, Australia (Ooi, Woods); West Australian Sleep
Disorders Research Institute, Queen Elizabeth II
Medical Centre, Perth, WA, Australia (McArdle,
Singh); Department of Pulmonary Physiology and
Sleep Medicine, Sir Charles Gairdner Hospital,
Perth, WA, Australia (McArdle, Singh); The
Memorial Hospital, Adelaide, SA, Australia (Rees);
Faculty of Human Sciences, University of Western
Australia, Perth, WA, Australia (Singh); The
Woolcock Clinic, University of Sydney, NSW,
Australia (Stow); Department of Otolaryngology/
Head and Neck Surgery, University of Washington,
Seattle (Weaver); Staff Surgeon, Seattle Veterans
Affairs Medical Center, Seattle, Washington
(Weaver); Flinders Centre for Epidemiology and
Biostatistics, College of Medicine and Public Health,
Flinders University, Adelaide, SA, Australia
(Woodman).
Author Contributions: Drs McEvoy and Woodman
had full access to all the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Concept and design: MacKay, Carney, Catcheside,
Chai-Coetzer, Chia, Cistulli, Hodge, Weaver, Woods,
Yeo, McEvoy.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: MacKay, Carney,
Catcheside, Chia, Cistulli, Hodge, Jones, Woodman,
Woods, Yeo, McEvoy.
Critical revision of the manuscript for important
intellectual content: MacKay, Catcheside,
Chai-Coetzer, Chia, Cistulli, Hodge, Jones,
Kaambwa, Lewis, Ooi, Pinczel, McArdle, Rees,
Singh, Stow, Weaver, Woodman, Woods, Yeo,
McEvoy.
Statistical analysis: Catcheside, Kaambwa, Weaver,
Woodman, Woods, Yeo.
Obtained funding: MacKay, Carney, Catcheside,
Chai-Coetzer, Cistulli, Ooi, Weaver, Woods, McEvoy.
Administrative, technical, or material support:
MacKay, Carney, Catcheside, Chai-Coetzer, Chia,
Jones, Ooi, Pinczel, McArdle, Rees, Stow, Woods.
Supervision: MacKay, Chai-Coetzer, Chia, Cistulli,
Hodge, Jones, Ooi, Rees, McEvoy.
Other - Trial PI: McEvoy.
Conflict of Interest Disclosures: Dr MacKay
reported receiving grants from National Health and
Medical Research Council of Australia, Flinders

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 Research Preliminary Communication
University, and The Repat Foundation 2013 Prabha
Seshadri Research Grant during the conduct of the
study and nonfinancial support from Genio-Nyxoah
and grants from Garnett-Passe Rodney Williams
Foundation and Illawarra Health and Medical
Research Institute outside the submitted work.
Dr Carney reported receiving grants from National
Health and Medical Research Council of Australia,
Flinders University, and The Repat Foundation
Prabha Seshadri Research Grant during the conduct
of the study. Dr Catcheside reported receiving
grants from National Health and Medical Research
Council of Australia and from Flinders University
during the conduct of the study; receiving grants
from the Cooperative Research Centre for
Alertness, Safety and Productivity, the National
Health and Medical Research Council of Australia,
and the Flinders Foundation Health Seed Grant and
nonfinancial support from Philips Respironics, Air
Liquide Healthcare, and Gorman Promed outside
the submitted work; having a patent to Sleep
Disorder Diagnosis, App No. AU 2018904007, US
62/812066 pending and a patent to decision
support software for sleep disorder identification,
February 28, 2019, US 61/815562 Sleep Disorder
Data Fidelity Management System, March 8, 2019,
pending. Dr Chai-Coetzer reported receiving grants
from the National Health and Medical Research
Council of Australia, Flinders University, and The
Repat Foundation during the conduct of the study.
Dr Cistulli reported receiving grants from the
National Health and Medical Research Council of
Australia, Flinders University, and The Repat
Foundation Prabha Seshadri Research Grant during
the conduct of the study and nonfinancial support
from ResMed Inc; nonfinancial support from Zephyr
Sleep Technologies; personal fees from SomnoMed,
Signifier Medical, Wolter Kluwers, and
Quintessence Publishing; and a provision of clinical
trial services from Bayer outside the submitted
work. Dr Jones reported receiving grants from
Illawarra Sleep Medicine Centre during the conduct
of the study. Dr Kaambwa reported receiving grants
from the Australian National Health and Medical
Research Council during the conduct of the study.
Dr Lewis reported receiving consulting fees for
Nyxoah SA (Belgium) as an investigator in 3 trials of
a new hypoglossal nerve stimulator for obstructive
sleep apnea. Dr Ooi reported receiving grants from
the National Health and Medical Research Council
and Flinders University during the conduct of the
study and personal fees from Medtronic outside the
submitted work. Dr Pinczel reported receiving
grants from the National Health and Medical
Research Council of Australia, Flinders University,
and The Repat Foundation during the conduct of
the study. Dr McArdle reported receiving grants
from the National Health and Medical Research
Council of Australia, Flinders University, and The
Repat Foundation Prabha Seshadri Research Grant
during the conduct of the study and grants from
Oventus (Brisbane, Australia), Nyxoah (Mont-Saint
Guibert, Belgium), and Zelda Therapeutics
(Australia) outside the submitted work. Dr Weaver
reported being a research consultant for Nyxoah SA
outside the submitted work and practicing sleep
surgery. Dr Yeo reported receiving grants from the
National Health and Medical Research Council of
Australia, Flinders University, Flinders University,
and The Repat Foundation Prabha Seshadri
Research Grant during the conduct of the study.
Dr McEvoy reported receiving grants from the
National Health and Medical Research Council of
1178 JAMA September 22/29, 2020 Volume 324, Number 12 (Reprinted)
© 2020 American Medical Association. All rights reserved.
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Effect of Upper Airway Surgery vs Medical Management on Obstructive Sleep Apnea
Australia, Flinders University, and The Repat
Foundation during the conduct of the study and
grants from Philips Respironics and ResMed outside
the submitted work. No other disclosures were
reported.
Funding/Support: This study is supported by a
project grant from the National Health and Medical
Research Council of Australia (1059510).
Supplementary trial funding was provided by
Flinders University and The Repat Foundation
Prabha Seshadri Research Grant. Dr McEvoy was
supported by a practitioner fellowship of the
National Health and Medical Research Council (GNT
1079785). Dr Catcheside was supported by an
Australian Research Council Future Fellowship
(FT120100510). Dr. Weaver’s effort was supported
by the Unites States National Institutes of Health
(R01 HL084139, PI Weaver) and the Veterans
Affairs Puget Sound Health Care System.
Role of the Funder/Sponsor: The sponsors had no
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication. The contents of this
article do not represent the views of the US
government.
Group Information: The Sleep Apnea Multilevel
Surgery (SAMS) Trial Group Investigators: 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 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; Nick A. Antic, PhD;
R. Doug McEvoy, MD. Data and safety monitoring
board: Matthew Naughton, MD (sleep and
respiratory medicine specialist; Alfred Hospital and
Monash University, Melbourne, Australia);
Nathaniel Marshall, PhD (clinical trialist,
epidemiologist, sleep disorders specialist;
University of Sydney and The Woolcock Medical
Institute, Sydney, Australia); and William Coman,
AM, MD (consultant ENT surgeon; University of
Queensland). Sleep laboratory managers: Jeremy
Mercer, PhD (Flinders Medical Centre); Terry Sands,
MD (Wollongong Hospital); Pam Singh, BSc(Hons)
(Royal Adelaide Hospital); Neill Madeira, BHealthSc
(Sir Charles Gairdner Hospital); Gary Cohen, PhD
(for Sydney site). Corelab manager: Jeremy Mercer,
PhD. Corelab scoring: Laura Bandick, BPsych(Hons);
Michaela O’Keefe, BPsych(Hons). Additional site
coordinators: Alison Teare, BSc, BEd; Kelsey
Johnson, BPsych(Hons); Natasha Umrigar,
BmedHlthSciAdv(Hons); Sue-Ellen Holmes, BSc
(Hons); Kate Sutherland, PhD; Aimee Lowth, BSc
(Hons); Clare Rea, BSc, BA.
Meeting Presentation: This study was presented
at the Australasian Sleep Association Conference;
October 19, 2018; Brisbane, Australia, and at the
virtual European Respiratory Society International
Congress; September 7, 2020.
Data Sharing Statement: See Supplement 3.
Additional Contributions: This work would not
have been possible without both the late Samuel
Robinson, MD (Flinders Medical Centre), who
pioneered the surgical technique and the late Nick
Antic, PhD (Flinders University). Dr Antic brought
together the collaboration of sleep physicians and
surgeons, led the funding proposal, and was the
study’s principal investigator before his untimely
death (in 2016). We thank the patients who
participated in this trial; the various clinical and
research teams of the Sleep and Respiratory, and
Otolaryngology Head and Neck Surgery
departments; and the technicians in the core sleep
laboratory at the Adelaide Institute of Sleep Health
for their work on the study.
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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: mas9390@med.cornell.edu

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
OSA,2 however, despite advancements in technology, poor
compliance continues to be a major barrier to treatment.3
Upper airway stimulation (UAS) therapy is an established
therapy for PAP-intolerant patients. The UAS system is
composed of three implantable components including a
programmable implanted pulse generator (IPG), a stimula-
tion lead with electrodes that are placed on the medial bra-
nches of the hypoglossal nerve, and an intercostal
respiratory sensing lead.4 The system is designed to sense
respiration and deliver synchronized stimulation to the
hypoglossal nerve, which causes stiffening and forward
protrusion of the tongue leading to the airway opening
during each inspiration. The efficacy of this therapy was
demonstrated in the Stimulation Therapy for Apnea
Reduction (STAR) trial.5
Data from patients treated with UAS as part of rou-
tine clinical care have been collected in the Adherence
and Outcome of Upper Airway Stimulation for the OSA
International Registry (ADHERE). Previous publications
of data from the Registry reported that the use of the
therapy was effective in AHI reduction, patients had high
levels of adherence, and the majority were more satisfied
with UAS than PAP. Review of ADHERE data found
older age and lower body mass index (BMI) associated
with therapy success. There was a trend toward women
having increased odds of therapy effectiveness.6–8
Since the last publication, the number of the
patients in the registry has almost doubled. This work
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
those above 32 kg/m2, which were not studied in the
STAR trial and is of interest to the clinicians.
MATERIALS AND METHODS
Study Design
ADHERE (NCT02907398) is an ongoing, international,
multicenter, observational registry designed to capture outcomes
of 5,000 patients implanted with the Inspire™ UAS System
(Inspire Medical Systems, Maple Grove, Minnesota). Manufac-
turer indications for implantation with the UAS system include
diagnosis of moderate to severe OSA (AHI 15–65 events/hr) with
less than 25% central/mixed apneas, intolerance or failure of
PAP treatment, and absence of complete concentric collapse at
the palatal level during drug-induced sleep endoscopy.
This registry includes patients undergoing standard of care
management following UAS implantation without any additional
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.
Sites are paid for data entry for each subject. Each subject
receives a stipend for participation in the registry. Stipends are
paid out after visits are completed. Current UAS therapy man-
agement protocol includes device activation 1 month after system
implantation, followed by patient self-adjustment for approxi-
mately 2–3 months. After self-adjustment, device optimization is
recommended during an in-lab polysomnography (PSG) at 3–
6 months post-implant. After initial therapy optimization,
patients are followed by annual visits to assess effectiveness of
the therapy with PSG or home sleep apnea testing (HSAT) and
Laryngoscope 131: November 2021
to provide necessary device setting adjustments. Sleep studies
performed during the annual visits do not include titration of the
UAS system and the AHI reported for these visits is a total or
all-night AHI. The registry captures data on each enrolled
patient through their first annual visit. However, the visit win-
dow for the first annual visit can be up to 2 years post-implant to
allow patients to get full therapy optimization. The registry pro-
tocol was reviewed and approved by each contributing center’s
institutional review board or ethics committee, and all patients
participating in the registry have provided informed consent.
Outcome Measurements
Demographic and baseline medical history information was
collected for all enrolled patients. Patients completed the
Epworth sleepiness scale (ESS) questionnaire, a self-reported
instrument of 8 questions that measures daytime sleepiness,
prior to UAS implantation and at 12-months postoperatively.
Sleep data were captured prior to UAS implantation and the
final visit using a PSG or HSAT with one implant setting during
the entire night study. The final visit collected the AHI from the
entire night of the sleep study. During the post-PSG therapy
optimization visit and at the final visit, clinicians rated patient’s
progress using the Clinical Global Impression Index (CGI-I), a
7-point scale to assess improvement or worsening of the patient’s
OSA burden as compared to before UAS implant. Patients filled
out a survey on UAS therapy satisfaction in comparison to PAP
at the post-titration and at the final visit. Therapy usage was
captured upon device interrogation at the post-titration and at
the final visit. Safety information, including device, surgical pro-
cedure, or therapy-related adverse events, was collected for the
time period spanning UAS implantation through the final visit.
Statistical Analysis
Data from all enrolled patients (n = 1,849) and those who
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
below 35 kg/m2 (n = 535). BMI-related outcome analysis was per-
formed by comparing two groups: patients with a baseline BMI
≤32 kg/m2 (BMI32, n = 438) and patients with baseline
32 < BMI ≤ 35 kg/m2 (BMI35, n = 97). Statistical significance was
determined using Wilcoxon rank-sums test for non-normal data
and t-test for normal data with an a priori significant threshold
of P < .05. If the results of the Wilcoxon rank-sum test or t-test
were non-significant, noninferiority testing was performed using
one-sided t-test for normally distributed data. The noninferiority
margin was set at five for AHI and two for ESS. The results were
reported as a mean  standard deviation. Sensitivity analyses
using multiple imputation method were performed to determine
the effect of missing data on the results.
RESULTS
A total of 1,849 patients were enrolled at 43 global
centers from October 19, 2016 to March 13, 2020. At the
time of data analysis, implant data were available for
1,768 patients. About 1,019 patients reached the time of
1–2 years post implant to be eligible to complete a final
follow-up visit. Of these patients, 823 (83%) had com-
pleted a final follow up visit, 782 of these patients
reported at least one of the following: AHI, ESS, Therapy
Use, Figure 1. The population was primarily comprised of
Suurna et al.: ADHERE Registry 2020 Update Impact of BMI
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).

Laryngoscope 131: November 2021 Suurna et al.: ADHERE Registry 2020 Update Impact of BMI
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.

Laryngoscope 131: November 2021 Suurna et al.: ADHERE Registry 2020 Update Impact of BMI
2620
Subanalysis of Two BMI Groups
BMI analyses included 535 subjects with AHI data
collected at both baseline and final visits and enrollment
AHI between 15 and 65 events/hr. There were no other
demographic differences between the two BMI groups.
Prevalence of hypertension was significantly higher in
the BMI35 group (59.8% vs. 45.0%, P = .01). No signifi-
cant difference between the groups was observed with
regards to other co-morbidities (Table I). The mean AHI
at baseline in the BMI32 group was 35.4  14.1 events/hr,
compared to the mean AHI in the BMI35 group of
37.1  14.5 events/hr. At the final follow-up, mean AHI in
the BMI32 group was 14.0  14.5 events/hr (a change of

21.4 events/hr), whereas the mean AHI in the BMI35
group was 16.8  15.1 events/hr (a change of
20.3
events/hr). The change in AHI for BMI35 group was non-
inferior to the change in AHI for the BMI32 group. The
mean difference in change in AHI between the two groups
was 1.07 with the upper 97.5% confidence interval at 4.5
which falls within the noninferiority margin. The results
were similar after performing sensitivity analyses using
multiple imputation to account for missing data at final
A 50.0
36.0
45.0
40.0
35.0
AHI (events/h)
30.0
25.0
20.0
15.0
10.0
5.0
0.0
Baseline
All Subjects (n=782)
B
20
11.4
15
ESS
10
0
Baseline
All Subjects (n=782)
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)
Laryngoscope 131: November 2021
visit (mean difference = 0.63, upper 97.5% confidence
interval = 4.3). Mean ESS in the BMI32 group decreased
from 11.6  5.5 at the baseline to 7.1  4.7 at the final
visit (a mean change of
4.5 points), whereas the mean
ESS in the BMI35 group decreased from 12.4  5.0 at the
baseline to 7.8  4.6 at the final visit (a mean change of

4.8 points). The mean difference in change in ESS
between the two groups was
0.23 with the upper 97.5%
confidence interval at 0.78 which falls within the non-
inferiority margin. The results were similar after performing
sensitivity analyses using multiple imputation to account for
missing data at final visit (mean difference =
0.16, upper
97.5% confidence interval = 0.91) (Table II, Fig. 2A,B). How-
ever, there was a significant difference in surgical success
rate using the Sher criteria defined as AHI reduction by
50% to below 20 events/hr (72.2% in BMI32 group vs. 59.8%
in BMI35 group, P = .02). Subjects with a higher BMI were
less likely to achieve an AHI < 20. There was a significant
difference in therapy use between the two BMI groups with
patients in the BMI32 using therapy a mean of 5.8  2.0 hr/
day compared to patients in the BMI35 group who used ther-
apy a mean of 5.2  2.2 hr/day (P = .028). Between the two
37.1
35.4
*p<0.05 compared to Baseline
16.8*
14.5* 14.0*
Final Follow-up
BMI32 (n=438) BMI35 (n=97)
*p<0.05 compared to Baseline
11.6 12.4
7.1* 7.1* 7.8*
Final Follow-up
BMI32 (n=396) BMI35 (n=84)
Suurna et al.: ADHERE Registry 2020 Update Impact of BMI
2621
 100%
80%
56%
60%
40%
20% 42%
0%
BMI32
Baseline
No OSA (AHI<5)
Fig. 3. Obstructive sleep apnea (OSA) Severity (by body mass index [BMI] group)
BMI groups, there were no differences in patient reported
therapy discomfort. BMI was also not a predictor for adjunc-
tive therapy use.
Both BMI groups had a significant number of
patients with change in OSA severity from the baseline to
final visit, with the percentage of patients with severe
OSA decreasing from 56% to 11% in the BMI32 group and
61% to 13% in the BMI35 group (Fig. 3) The BMI35 group
reported slightly higher adverse event rates (SAE: 4.1%;
non-SAE: 29.9%) compared to the BMI32 group (SAE:
2.3%; non-SAE: 24.7%), however, due to sample size, sta-
tistical comparison of these adverse event rates is not
appropriate. Clinician assessment using CGI-I and
patient satisfaction was similar between groups. Both
groups had high self-reported patient satisfaction with
the UAS therapy (Table II).
DISCUSSION
The ADHERE registry has grown to include 1,849 par-
ticipants worldwide. These results represent the 2020
update which is the largest analysis of UAS therapy to date.
Consistent with previously published therapy outcomes,
therapy use continues to demonstrate significant reduction
of mean AHI from 36.0 to 14.5 events/hr with normalization
of ESS.5–8 Mean therapy use of 5.6 hr/day is consistent with
previously reported ADHERE results.6–8
This update on therapy safety demonstrates a low
rate of adverse events. Reported therapy-related discom-
fort included stimulation-associated tongue abrasions and
insomnia/arousals that had a significant negative effect
on AHI reduction and therapy use. However, discomfort
did not negatively affect subjective symptoms based on
ESS. These results suggest that assessing and addressing
discomfort early in the postimplant care process is critical
to long-term therapy adherence. Patients’ complaints of
therapy discomfort during follow up visits or after PSG
therapy titration should ideally be addressed immedi-
ately. Therapy setting adjustments by changing electrode
configuration, therapy start delay, pulse width and fre-
quency can allow for more comfortable therapy use and
potential improvements in effectiveness. Use of a dental
Laryngoscope 131: November 2021
2622
11% 13%
19%
61% 32%
40%
30%
37%
30% 25%
BMI35 BMI32 BMI35
12 - Month
Mild Moderate Severe
guard has helped address discomfort concerns related to
tongue abrasion. Overall, the rate of serious adverse events
remains low. Device revision was required in 1.9% of cases,
with the respiratory sensor lead revision being the most
common. Attention should be given to patients who report
sudden change in stimulation pattern or strength, new or
worsening pain, and signs of infection at the sites of the
implant. Device testing and appropriate imaging in such sit-
uations can help detect hardware issues.
Several reports have suggested that use of adjunc-
tive therapy, such as chin strap, oral appliance, and
UPPP, can improve UAS therapy outcomes and adher-
ence.9–11 Nevertheless, prior ADHERE analysis has not
demonstrated an association between other upper airway
surgeries and UAS efficacy.12 Positional OSA was also
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
patients using UAS as their only OSA treatment at final
visit. These results suggest that UAS is often effective as
a monotherapy, however, individualized combination
therapy should still be considered in patients with sub-
optimal treatment response.
All patients implanted in the STAR trial had a BMI
less than 32 kg/m2. This criterion has been required for
patient selection by many insurance coverage policies,
and UAS efficacy in patients with BMI > 32 kg/m2 is still
debated. Potential UAS efficacy in patients with higher
BMI has been suggested by Huntley et al. who reported
no difference in UAS therapy success rates between
BMI > 32 kg/m2 and BMI < 32 kg/m2 groups.14 However,
this study reported AHI data from 2-months PSG titra-
tion studies, as opposed to full-night AHI which is
reported in the current ADHERE update. The data analy-
sis of the two BMI groups (BMI32 and BMI35) indicated
that although the change in AHI for patients in the
BMI35 group is noninferior to the change in AHI for
patients in the BMI32 group, subjects with a higher BMI
had a significantly lower likelihood in meeting Sher surgi-
cal success criteria secondary to an inability to achieve an
AHI < 20 events/hr. Even though patients in both groups
have met DISE criteria for therapy indication, higher
Suurna et al.: ADHERE Registry 2020 Update Impact of BMI
BMI is associated with an increase in airway closing pres-
sure which might not be fully overcome with comfortable
UAS settings, thus leaving patients with higher residual
AHI. Analyses further indicated lower therapy usage in
patients with higher BMI. However, the higher BMI
group (BMI35) experienced similar reductions in AHI and
there was a significant reduction of OSA severity with
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
and therapy usage between the BMI groups, there was no
significant difference in addressing the patients’ subjective
symptoms. Reduction of sleepiness with the therapy use
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-
ment for patients with moderate to severe OSA and
BMI > 32 kg/m2. It should be noted that patients in the
BMI35 group had higher prevalence of baseline hyperten-
sion. Considering that untreated OSA is associated with
increased risk of developing new-onset hypertension and is
a modifiable risk factor,15 higher BMI patients should be
considered for UAS implantation if unable to tolerate PAP.
ADHERE continues to gather data on outcomes,
adverse events, and therapy satisfaction in patients
implanted with UAS as part of regular clinical care. This
publication reports outcomes from the largest cohort of
patients using UAS to date. Lack of standardization in
polysomnography outcomes reported by individual institu-
tions has been an ongoing concern.16 The registry collects
and reports total AHI using full night PSG or HSAT at
final visit which addresses previous concerns of reporting
only treatment AHI from the titration polysomnogram.
Nevertheless, it is not possible to mandate absolute unifor-
mity of diagnostic testing equipment and treatment proto-
cols between institutions implanting patients with OSA as
part of regular clinical care. The registry reports outcomes
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.
Inability to present final visit data for every enrolled
ADHERE patient is a limitation of the study. Even though
reasons for loss to follow-up have not yet been studied, pre-
dominant association with either good or bad therapy
experience can sway the reported outcomes. Nevertheless,
the results reported in this publication further address fac-
tors that impact UAS outcomes, with special focus on
therapy-related discomfort and BMI. Although this is a
registry study, institutions are reimbursed for their time
to record the data in the study database. In addition, mul-
tiple physicians who have contributed to the data pres-
ented in this manuscript have received honoraria from the
registry sponsor, which is a potential source of bias and
limitation of the study.
CONCLUSION
This interval update on ADHERE registry outcomes
demonstrates efficacy, safety, and high adherence rates
for UAS therapy. Although there are differences in Sher
Laryngoscope 131: November 2021
surgical success rate outcomes, AHI reduction, ESS
improvement, and therapy satisfaction are similar
between patients with BMI32 and BMI35. Consistent use
is imperative for therapy efficacy and is affected by dis-
comfort. Therapy-related discomfort should be addressed
early in the process of therapy optimization to improve
UAS adherence and outcomes.
ACKNOWLEDGEMENTS
We acknowledge all investigators and research coordina-
tors at 43 participating centers for their contribution of
data collection in the ADHERE Registry.
CONFLICT OF INTEREST
M.V.S. has received honoraria from Inspire Medical; A.
S. has received honoraria and covered travel expenses for
invited talks on behalf of Inspire Medical; M.B. has received
research support and is a consultant for Inspire Medical;
R.D.P. has received honoraria from Inspire Medical; C.H. has
received research grant, travel support and consulting
honoraria from Inspire Medical; C.H. has received research
support from Inspire Medical; C.L. is a consultant for
Inspire Medical; J.T.M. received honoraria from ImThera
Medical, is a consultant and received honoraria from
Inspire Medical, is a consultant and received honoraria
from Nyxoah Medical, has received honoraria and travel
reimbursement from Neuwirth Medical Products; R.S.
received research support from Inspire Medical, consultant
for Smith & Nephew, Cryosa Inc, Invicta Medical, Inspire
Medical, Galvani Bioelectronics, Enhale Medical; N.D.V. is a
researcher for Inspire, Nyxoah, on medical advisory board
for Philips NightBalance; H.W. serves as the principal
investigator of the studies with Inspire at Cleveland
Clinic, has received funding from Resmed; E.T. has received
a research grant from Inspire Medical.
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