Journal of

Otorhinolaryngology, Hearing
and Balance Medicine

Review
Diagnosis and Management of Obstructive Sleep Apnea:
Updates and Review
Shan Luong 1, *, Liz Lezama 2 and Safia Khan 3,4

1 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas
Southwestern Medical Center, Dallas, TX 75390, USA
2 Department of Pediatrics, Pediatric Pulmonology Fellowship Program, University of Texas Southwestern
Medical Center, Dallas, TX 75390, USA; [email protected]
3 Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;
[email protected]
4 Department of Family and Community Medicine, University of Texas Southwestern Medical Center,
Dallas, TX 75390, USA
* Correspondence: [email protected]

Abstract: Obstructive sleep apnea (OSA) is a heterogenous disease process that cannot be adequately
categorized by AHI alone. There is a significant prevalence of OSA in the general population with
ongoing efforts to evaluate the risk factors contributing to OSA and its associated clinical implications.
Only by improving our understanding of OSA can we advance our methods in the diagnosis and
treatment of OSA. For this article, the authors reviewed keywords of obstructive sleep apnea diagnosis
and therapy in the databases of Embase, Medline, and Medline ePub over the past 3 years, excluding
any articles that only addressed sleep apnea in children under age 17 years. This review article is
divided into three main sections. First, we will investigate the use of novel screening tools, biomarkers,
anthropometric measurements, and novel wearable technologies that show promise in improving
the diagnosis of OSA. There is mention of comorbid conditions seen in OSA patients since certain
disease combinations can significantly worsen health and should raise our awareness to diagnose
and manage those concomitant disorders. The second section will look at the current and developing
treatment options for OSA. These include positive airway therapy (PAP), mandibular advancement
device (MAD), exciting new findings in certain medications, orofacial myofunctional therapy (OMT),
hypoglossal nerve stimulation therapy (HGNS), and other surgical options. We will conclude with
Citation: Luong, S.; Lezama, L.; Khan,
a section reviewing the current Clinical Practice Guidelines for Diagnostic Testing in Adults with
S. Diagnosis and Management of
Obstructive Sleep Apnea from 2017, which strongly advises polysomnography (PSG) or home sleep
Obstructive Sleep Apnea: Updates
apnea testing (HSAT), along with comprehensive sleep evaluation for uncomplicated patients with a
and Review. J. Otorhinolaryngol. Hear.
Balance Med. 2024, 5, 16. https://
clinical presentation of OSA.
doi.org/10.3390/ohbm5020016
Keywords: heterogeneity in OSA; updates in OSA; diagnosis of OSA; treatment of OSA
Academic Editor: Yu Sun

Received: 24 August 2024

Revised: 25 October 2024
Accepted: 26 October 2024 1. Introduction
Published: 29 October 2024 Obstructive sleep apnea is a chronic disorder of sleep and breathing, with a prevalence
of 13% among men and 5% among women, approximately 39 million individuals in
the United States of America [1]. Worldwide and nationwide studies to determine the
Copyright: © 2024 by the authors.
prevalence of sleep apnea have shown higher rates of undiagnosed individuals compared
Licensee MDPI, Basel, Switzerland.
to other chronic diseases despite having a much higher prevalence of the main presenting
This article is an open access article
symptom of snoring [1]. This is suggestive of areas for improvement in the diagnosis
distributed under the terms and of OSA: an increase in recognition and referral for OSA evaluation and timely access to
conditions of the Creative Commons accurate and cost-effective sleep studies. This article will investigate some of the areas
Attribution (CC BY) license (https:// of research over the past few years in the advancement of our understanding of OSA. A
creativecommons.org/licenses/by/ keyword search for obstructive sleep apnea novel therapy and diagnosis was performed
4.0/). using the databases of Embase, Medline, and Medline ePub over the past 3 years. More

J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16. https://doi.org/10.3390/ohbm5020016 https://www.mdpi.com/journal/ohbm

J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 2 of 11

than 2000 published works were identified, and the search was narrowed to human studies
and articles in English. Any studies and articles that solely addressed children under the
age of 17 years were excluded.
The framework of this review includes three main sections: screening and diagnosis,
treatment, and current guidelines for the diagnosis of obstructive sleep apnea.

2. Part I: Screening and Diagnosis of Obstructive Sleep Apnea

Increasingly, it has been recognized that obstructive sleep apnea (OSA) is a heterogenous
disease process that cannot be reliably characterized by AHI alone [2]. Prior studies suggest
that there are different endotypes and phenotypes that can impact prognosis and should lead
to a more precise treatment plan [2]. Ye and colleagues [3] found three distinct phenotypes
in OSA patients through a cluster analysis of patient-centric questionnaires. Cluster 1 was
the “disturbed sleep group” with predominant insomnia-related symptoms, cluster 2 was the
“minimally symptomatic group”, and cluster 3 was the “excessive daytime sleepiness group”.
The three clusters had no observable statistical difference in sex, BMI, AHI, ODI, or minimum
oxygen desaturation, but cluster 2 patients, who had the fewest symptoms, ended up with the
highest probability of having comorbid hypertension, diabetes, and cardiovascular disease [3].
This clinical implication has led to further pursuit in the understanding of the heterogeneity
of OSA to improve the diagnosis and treatment of the disorder.

2.1. Additional Screening Tools for OSA

Clinicians have largely relied on the validated STOP-BANG questionnaire to assess risk
for OSA, with ≥3 out of 8 parameters as a cutoff. The screening tool includes four self-reported
symptoms (loud snoring, excess daytime sleepiness, witnessed sleep apnea, and hypertension)
and four physical traits (BMI > 35, age > 50 years, neck circumference > 40 cm, and male
gender). It has previously been observed that Asians can have increased cardiovascular risk at
a lower BMI compared to other ethnicities/races, and the World Health Organization (WHO)
already has a lower cutoff of BMI for obesity in Asians. Lee et al. [4] proposed a modified
STOP-BANG questionnaire for the Korean population and found that when the BMI threshold
was lowered to 30 as compared to 35, and with a cutoff score of ≥4, it remained a valid
alternative screening tool for OSA in the Korean population.
Koseoglu et al. [5] evaluated a previously proposed Lausanne NoSAS score (Neck
circumference, Obesity, Snoring, Age, Sex) as a new tool for OSA screening and prediction
for other health complications. The scores range between 0 and 17 points, with scoring
as follows: neck circumference > 40 cm as 4 points, BMI 25–30 as 3 points, BMI ≥ 30 as
5 points, snoring as 2 points, age > 55 years as 4 points, and being male as 2 points. A
score of ≥8 is indicative of high risk for OSA, and they also found that the scores were
statistically higher in patients with concomitant diseases. The authors proposed that the
NoSAS score may be useful to help predict other disease comorbidities, especially CVD in
patients with OSA.
Morning dry mouth is commonly reported among patients with OSA. Ma et al. [6]
found that morning dry mouth was associated with loud snoring, observed sleep apnea,
and excessive daytime sleepiness and suggested this parameter may be underutilized and
could enhance the current OSA screening.

2.2. Utility of Biomarkers for OSA Diagnosis

The usage of biomarkers has been studied to augment phenotyping approaches. There
are a few biomarkers undergoing further investigation in the hopes of improving the
diagnosis of OSA and monitoring its control. One such biomarker is adiponectin (AP), a
protein present in adipose tissue that helps to reduce blood glucose, lipid level, and insulin
resistance and has anti-inflammatory and anti-atherosclerotic properties. AP was studied
and found to be decreased in adipocytes exposed to intermittent hypoxia when studied
in vitro [7]. Since obesity has been shown to be associated with OSA, Li et al. [8] examined
AP levels in patients with OSA compared to patients with simple snoring and found a
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 3 of 11

progressive decrease in AP levels as AHI increased. Serum AP had a sensitivity of 88.9%

and a specificity of 78.9% in diagnosing OSA, with the potential to be used as an additional
monitoring index for the diagnosis and treatment of OSA [8].
Another biomarker studied is the claudin (CLDN) protein family. CLDNs are expressed
in the intestinal mucosa, amongst other epithelia. CLDN1 and CLDN3 are part of the “tight
sealing claudins”, and CLDN2 is part of the “leaky pore-forming claudins” [9]. There is
dynamic regulation of CLDN protein in response to mucosal inflammation in inflammatory
bowel disease (IBD) that can further compromise the intestinal epithelial barrier and perpetu-
ate the inflammatory response [9]. There is also an association between OSA and higher levels
of gut barrier dysfunction biomarkers with the implication that OSA can cause tight junction
malfunction, which enhances gut bacterial translocation and propagates low-grade systemic
inflammation [9]. Liu et al. [10] studied plasma and urinary CLDN1, CLDN 2, and CLDN3
levels and found them to be significantly decreased in the OSA group compared to the control
group. The urinary CLDN levels had a sensitivity of 100% but with a lower specificity ranging
from 42% to 67%, while the plasma CLDN levels had a sensitivity ranging from 62% to 85%
and a specificity of 42% to 75%. The combination of urinary and plasma CLDN levels can
be an area of further study as a potential screening tool for OSA [10]. Interestingly, CLDN1
was studied in the normal blood–brain barrier (BBB) and noted to be rarely expressed [11]. In
pathological conditions of the brain, including the post-stroke state, the level of CLDN1 was
found to be increased and was associated with BBB hyperpermeability that tended to be more
damaging for post-stroke recovery [12].
Sclerostin is a glycoprotein involved in vascular calcification and is studied in the
OSA patient population due to the increased frequency of associated comorbid cardiovas-
cular disorders [13]. Leukocyte cell-derived chemotaxis-2 (LECT2) is a protein expressed
in various cell lines, including endothelial cells and smooth muscle cells, and has anti-
inflammatory and antiatherogenic effects. It is theorized that in OSA, recurrent episodes
of hypoxia can increase the release of cytokines that cause endothelial smooth muscle
proliferation and fibrosis. These two biomarkers were studied in OSA patients and were
found to be more elevated compared to the control group. Amongst the OSA patients,
the levels were higher in severe OSA patients compared to mild OSA patients. These
biomarkers may help to screen for the presence of OSA [14].
A hematologic parameter known as the neutrophil-to-lymphocyte ratio (NLR) calcu-
lated from a complete blood count (CBC) has been used to evaluate systemic inflammation
and stress. It is influenced by many conditions, and the normal range is between 1 and 2,
whereas values higher than 3 and less than 0.7 are considered pathological in adults [15].
NLR in the gray zone between 2 and 3 may be an early warning of pathological pro-
cesses [15]. This marker has been used in the monitoring of cancer-related inflammation
and as an indicator of prognosis in solid tumors. The NLR has also been evaluated in the
diagnosis and prognosis of patients with COPD. Yang et al. [16] studied NLR in patients
with COPD, OSA, and overlap syndrome and found it to be higher in those with overlap
syndrome at 2.9 compared to COPD alone at 2.5 and OSA alone at 2 (p = 0.02). This may
help increase the clinical suspicion of comorbid OSA in patients with COPD.

2.3. Utility of Anthropometric Measurements for OSA Diagnosis

Physical measurements of the nasal cavity size, tongue size and strength, pharyngeal
structures and associated dynamic changes, diaphragmatic movements, and breath volume
have been studied in OSA patients. Loureiro et al. [17] did not find the internal nasal cavity
dimension to be a risk factor for OSA.
The addition of awake endoscopy has been helpful in evaluating upper airway
anatomy and airway obstruction patterns between the upright and supine positions [18].
Tongue depression strength was noted to be reduced in the group of OSA patients with
more severe tongue base collapse [18]. Increased tongue thickness and decreased tongue
stiffness measured through shear wave ultrasound elastography were observed in patients
with OSA [19]. This is not surprising, as increased tongue fat has been observed in patients
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 4 of 11

with OSA. This may further increase interest in studying tongue-strengthening exercises
and the utilization of tongue-strengthening devices in the OSA patient population.
Chen et al. [20] studied the characteristics of diaphragms in OSA patients and noted
that patients with higher AHI tend to have thicker diaphragms with more stiffness. The
main influencing factor was found to be the oxygen desaturation index, suggesting that
nocturnal intermittent hypoxia was a risk factor for diaphragmatic hypertrophy and impaired
diaphragmatic contractility [20]. Lim et al. [21] evaluated breath volumes and found that
when subjects were exposed to small negative pressure at −3 cmH2 O to induce upper airway
collapsibility, their decrease in their breath volume correlated with an increase in AHI severity.
This seems to be a promising way to assess OSA severity in a simpler and quicker manner.
Of note, drug-induced sleep endoscopy is the current preferred diagnostic technique
to assess the dynamic upper airway in a state that mimics natural sleep in patients with
obstructive sleep apnea. This study aids sleep surgeons in knowing the areas of upper
airway collapse to select patients who may improve with surgical interventions if they are
not tolerant to the standard CPAP treatment. Many drugs are available to achieve sedation
to induce N2 sleep. The patient is typically examined in the supine decubitus position,
though some patients are also examined in the lateral decubitus position if that is their
preferred sleeping position. There is an updated recommendation to use the modified
VOTE classification to evaluate the velum, oropharyngeal walls, tongue base, and epiglottis
for the shape of collapse (antero-posterior, lateral, and concentric) and identify the main
structural cause of that collapse [22]. DISE is thus a useful tool to further identify the
anatomic site of upper airway collapse in patients who snore or have OSA and who are not
tolerant to CPAP and desire surgical intervention.

2.4. Novel Diagnostic Technologies for OSA

Since 2019, the FDA has approved nine additional OSA-detecting wearables for home
sleep testing. Chiang et al. [23] have divided the technologies into a group utilizing
photoplethysmography (PPG) data that are peripheral arterial tonometery (PAT)-based
devices or those devices that are either acoustic-based or respiratory effort-based. FDA-
approved wearables utilizing PPG data include NightOwl, ANNE Sleep, Somfit, Belun Ring,
and SleepImage SaMD. Effort-based wearable devices include Sunrise and Wesper Lab.
Acoustic devices analyze the snoring characteristics to identify OSA and include AcuPebble
and BresoDX1, which employ acoustic sensors (microphones) positioned over the anterior
neck to capture signals related to respiratory, cardiac, and movement sounds. Sanchez
Gomez et al. [24] found that compared to the gold standard in-lab polysomnography, the
acoustic device AcuPebble SA100 had a diagnostic accuracy of 95% for OSA.
The hypoxic burden is the area under the desaturation curve associated with respira-
tory events, which is calculated in diagnostic sleep studies. Major adverse cardiovascular
events (MACE) include myocardial infarction, stroke, exacerbation of congestive heart fail-
ure, revascularization procedures such as percutaneous coronary intervention and coronary
artery bypass graft surgery, and all-cause death. Trzepizur et al. [25] found that the hypoxic
burden was better associated with MACE than AHI. AHI provides a simple count of the
number of obstructive episodes but does not factor in the duration and depth of respiratory
disturbance. The hypoxic burden can better characterize nocturnal respiratory events and
predict MACE incidence and is easily calculable using current polysomnography.

2.5. Screening for Comorbid Conditions in OSA Patients

OSA has been associated with many comorbid conditions, and a more tailored screening
and testing approach could help improve the diagnosis and management of these diseases.
These other comorbid disorders include insomnia, periodic limb movement disorder (PLMD),
depression, hypertension, cardiovascular disease (CVD), stroke and cerebrovascular disease,
memory impairment, overlap with chronic obstructive pulmonary disease (COPD), asthma,
GERD, temporomandibular joint disorder (TMD), diaphragmatic impairment, and others.
Patients with OSA and insomnia may benefit from a multi-night home sleep study measure-
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 5 of 11

ment rather than a single-night PSG to better capture the variations in sleep disturbances
from insomnia [26]. There was noted longer sleep onset latency and lower sleep efficiency
in the concomitant insomnia group that was more adequately captured through multi-night
home studies. These factors are important as insomnia could negatively impact adherence
to PAP therapy, and these patients may benefit from additional hypnotics. OSA patients
who are greater than 50 years of age, have concomitant insomnia, and have an Epworth
sleepiness scale (ESS) of <10 were noted to have a 67-time increased likelihood of having
elevated periodic limb movements [27]. Patients who screen positive for all three parameters
would benefit from additional detailed evaluation for PLMD and restless legs syndrome.
Patients with overlap syndromes of OSA with COPD seem to have a poorer prognosis
in health. They tend to have a higher weight, body mass index (BMI), carbon dioxide reten-
tion, lower oxygen level, decreased sleep duration, decreased sleep efficiency, increased
arousal, and more vulnerability to developing pulmonary hypertension compared to either
disorder alone [28]. Patients with overlap syndrome also had an increased incidence of
cognitive impairment at 78%, compared to the OSA group at 57% incidence, the COPD
group at 29% incidence, and the normal control group at 8% incidence [29]. An increase in
awareness of comorbid cognitive impairment in patients with overlap syndrome would
help providers to screen for it earlier on. This would impact a patient’s overall health
and their ability to comply with therapy. Other studies have examined the difference in
brain anatomy and functioning in OSA patients. Selcuk et al. [30] found that there was
a significant decrease in the volume of right putamen gray matter on brain imaging in
OSA patients. The putamen is involved in motor control, learning, and emotions. Shi
et al. [31] also found a difference in the structural connectivity and functional connectivity
in the brains of OSA patients, which might lead to abnormal information transmission and
communication in the brain network.
OSA patients were noted to have more temporomandibular joint disorder in a case–
control study [32] and more periodontic disease in a retrospective study in the Korean
population [33]. This should help prompt an earlier referral for oral care. OSA was
more prevalent in patients who have asthma and was associated with poorer control
in a prospective study in the Japanese population [34]. There is a higher prevalence
of atrial fibrillation in patients with OSA, especially if they are older in age and have
hypertension [35].

3. Part II: Current and Developing Treatments for Obstructive Sleep Apnea
3.1. Positive Airway Therapy
Positive airway pressure (PAP) therapy, either by continuous (CPAP) or bilevel pres-
sure (BPAP) delivery devices, has remained the gold standard in treating patients with
obstructive sleep apnea across mild, moderate, and severe categories. The PAP devices
deliver pressurized room air through a nasal or oronasal mask interface. Equipment mainte-
nance involves cleaning the mask, hose/tubing, and water reservoir and switching out the
filters as directed by the manufacturer. Traditionally, therapy adherence to CPAP and BPAP
devices has ranged between 29% and 83% at most sleep centers at short-term and long-term
follow-ups [36]. This indicates sub-optimal management of this chronic sleep disorder
among patients who have poor tolerability to the pressure or the mask interface. Patients
who can successfully use PAP therapy benefit from the treatment of OSA and usually only
require annual follow-ups for minor pressure or mask adjustments. Significant improve-
ment in Epworth Sleepiness Scores and Quality of Life questionnaires are a testament to
the success of this treatment option. Sgaria et al. [37] noted that PAP therapy decreased
nocturnal symptoms, regurgitation, and daytime sleepiness and improved emotional and
social interactions in patients with OSA.

3.2. Mandibular Advancement Device

Amongst other non-invasive treatment options is the mandibular advancement de-
vice (MAD) custom-fit by sleep dentists, which is approved for the treatment of mild to
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 6 of 11

moderate OSA and also for patients who do not tolerate CPAP. MAD allows anterior and
inferior movement of the jaw to increase the pharyngeal area [38]. The devices usually
allow for adjustable advancement. Side effects include jaw pain, tenderness of teeth, and
hypersalivation. These devices, however, are not typically equipped with usage-tracking
sensors, which makes it difficult to monitor their efficacy and patient adherence to therapy.

3.3. Positional Therapy

Positional OSA patients have elevated AHI in the supine position compared to a
normal AHI in the non-supine posture. These patients have a favorable ability to stiffen and
dilate the airway in the lateral position so that the velopharynx becomes more circular [39].
Various devices have been designed for positional therapy, including tennis balls, pillows,
bulky backpacks, and positional alarms. Side effects include discomfort and back pain
and are not recommended for those who cannot sleep in the supine position during sleep.
Positional therapy is less effective compared to CPAP in reducing AHI but is shown to be
better at lowering lower ESS and AHI compared to no treatment [40].

3.4. Medications
Currently, medications have not yet been approved for the treatment of obstructive
sleep apnea but are under further investigation. Medications of the glucagon-like peptide
receptor (GLP-1) agonist class have been shown to support successful weight reduction and
have great potential for improving the severity of obstructive sleep apnea. These medica-
tions include semaglutide and liraglutide administered in the form of weekly subcutaneous
injections. Eli Lilly and Company recently released updates from the SURMOUNT-OSA
phase 3 clinical trials that show tirzepatide, which is a long-acting, glucose-dependent
insulinotropic polypeptide (GIP) receptor and GLP-1 receptor agonist, leading to a mean
AHI reduction of 63% (about 30 breathing events per hour fewer) in patients with OSA.
Apart from weight loss medications, the combination of atomoxetine (a norepinephrine
reuptake inhibitor) and oxybutynin (antimuscarinic) has also been shown to improve OSA
severity via a 63% reduction in AHI [41]. The noradrenergic and antimuscarinic effects
improve genioglossus muscle activity and upper airway patency during sleep. Either drug
administered separately did not reduce the AHI but, in combination, greatly reduced the
severity of AHI [41]. Another study further evaluated the combination of atomoxetine-
oxybutynin with zolpidem compared to atomoxetine-oxybutynin with a placebo to see if
zolpidem can improve night-time sleep without daytime impairment. The study found that
the addition of zolpidem helped increase sleep efficiency by 9% (p = 0.037) determined via
PSG, likely by increasing the threshold for respiratory arousals [42]. The participants did
not report worsening subjective daytime sleepiness but were noted to have more steering
deviation on a next day driving simulation test, suggesting increased objective sleepiness [42].
As medications can be helpful for sleep, they could also interfere with sleep. It is
recommended to review medications when treating patients with sleep disorders and adjust
medications that can lead to interruptions in sleep. A common example is the use of diuretics
in the evenings, which worsens nocturia. This can be mitigated by changing the timing of the
dose to earlier in the day. Also, patients ingesting opioids for the control of chronic pain can
have worsening in both central sleep apnea and obstructive sleep apnea events.

3.5. Orofacial Myofunctional Exercise Therapy

Orofacial myofunctional exercise therapy (OMT) can improve the severity of obstruc-
tive sleep apnea by reducing tongue fat and increasing the endurance and strength of the
genioglossus muscle [43]. Thus, this type of therapy shows usefulness for patients aversive
to other therapy options and for those with very mild symptoms and disease severity.
New devices that incorporate OMT are undergoing proof-of-concept trials to evaluate
its usefulness. A current FDA approved device is a neuromuscular electrical stimulator,
eXciteOSA. This device is a removable intraoral mouthpiece that delivers neuromuscular
stimulation to the intrinsic and extrinsic muscles of the tongue (mainly the genioglossus
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 7 of 11

muscle) during the daytime to increase muscle tone, preventing excessive muscle relax-
ation during sleep. The therapy consists of a series of pulse bursts with rest periods. Its
recommended use is for 20 min a day during wakefulness for at least 6 weeks to achieve
muscle strength. It is intended for use in patients older than 18 years of age with snoring
and mild obstructive sleep apnea (AHI < 15/h) [44].

3.6. Hypoglossal Nerve Stimulation Therapy

A hypoglossal nerve stimulator (HGNS) implant has been approved for moderate to
severe OSA patients who have failed CPAP therapy. The HGNS works by improving the
tone of the unilateral genioglossus muscle. This has been shown to support a reduction of
AHI by 50% from baseline, with AHI usually < 20 events/hour per the Stimulation Therapy
for Apnea Reduction (STAR) trial. These results were consistent at short- and long-term
follow-ups [45].
HGNS therapy involves the implantation of an impulse generator in the chest at-
tached to a sensing lead and a stimulation lead that coordinates the forward protrusion
of the genioglossus muscle as the patient exerts an effort during inspiration. While the
HGNS device is not a novel treatment option for OSA, the transition from a three-incision
to a two-incision surgical approach has shown statistically significant improvement in
waveform syncing and general device impression [45]. The two-incision surgery entails a
sub-clavicular incision for the neurostimulator impulse generator and a submandibular
incision for the stimulation electrode.
Implanted devices similar in technique to the above-mentioned hypoglossal nerve
stimulator are in the trial phases and may show significant results by the time of publication
of the next update for this review. Among these devices is the bilateral hypoglossal nerve
stimulator. This requires a single submandibular surgical incision for implantation of an
electrode that stimulates the bilateral hypoglossal nerves when activated by an external
rechargeable electrode placed (by means of an adhesive tape) directly above the implanted
electrode [46]. This device has been shown to support the improvement of AHI by more
than 80% in test trials, indicating promising results for large-scale phase III trials.

3.7. Other Surgical Options

Sleep surgery is an alternative treatment for patients who cannot tolerate PAP therapy.
These surgeries improve the stability of the upper airway to change the critical negative
closing pressure. The surgical algorithm for OSA includes preoperative evaluation with
detailed history and physical examination of the head and neck, visualization with imag-
ing, nasopharyngoscopy, and drug-induced sleep endoscopy to identify anatomic and
functional causes of obstruction for surgical planning, as well as diagnostic sleep study
with either PSG or ambulatory at-home sleep test to gauge the severity of the sleep apnea.
The first target of therapy is to optimize PAP or oral appliance therapy. In patients with
obesity, bariatric surgery evaluation and treatment should also be considered, as upper
airway surgery decreases in efficacy with increasing BMI.
Upper airway surgeries include intranasal surgeries such as septoplasty, turbinoplasty,
and nasal valve surgery to improve nasal airway patency and reduce nasal resistance and
mouth breathing. These surgeries have limited efficacy in reducing AHI, but they can
improve sleep quality, OSA-related sleep symptoms, and PAP compliance [47]. Next is
nasal floor expansion for patients with narrow and high-arch maxilla through distraction
osteogenesis with maxillary expansion. Uvulopalatopharyngoplasty is the most performed
sleep surgery, with updated techniques that have been more effective than classic UPPP [47].
It is precluded in patients who have a complete concentric collapse of the soft palate (velum)
seen during DISE. Tongue base reduction includes lingual tonsillectomy and removal of
the base of tongue fat but can be associated with higher costs and post-operative complica-
tions [47]. Genioglossus advancement is usually performed in conjunction with UPPP and
maxillomandibular advancement, which allows greater tongue advancement during sleep.
Maxillomandibular advancement (MMA) is one of the most effective surgical interventions
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 8 of 11

that involve osteotomies of the maxilla and mandible, followed by advancement to increase
the volume for intraoral soft tissue structures and stability of the upper airway dilator
muscles. This procedure is also reliable for those patients with concentric and lateral pha-
ryngeal wall collapse seen on DISE. The hypoglossal nerve stimulator is discussed earlier
in this paper but is precluded in those with complete concentric collapse of the oropharynx.

4. Part III: Summary of Current Obstructive Sleep Apnea Diagnosis Guidelines

from 2017
The 2017 guidelines focused on diagnostic updates on OSA. The diagnostic assessment
of OSA must encompass a comprehensive sleep evaluation, along with polysomnography
as the gold standard test. The recommendations strongly advised against the use of clinical
tools such as questionnaires or algorithms (Berlin Questionnaire, Epworth Sleepiness
Scale, Stop-Bang, and Multivariable Apnea Prediction Questionnaire) in the absence of
polysomnography (PSG) or a home sleep apnea test (HSAT) due to a lack of accuracy,
resulting in poor diagnostic value [48]. PSG or HSAT with a technically adequate device is
recommended for the diagnosis of OSA in uncomplicated adults with clinical presentation
suggesting the risk of moderate to severe OSA. The clinical presentation of OSA includes
the presence of excessive daytime sleepiness and at least two of the three criteria: habitual
loud snoring, witnessed apneas, gasping or choking, or previously diagnosed hypertension.
HSAT was found to be less sensitive than PSG in the diagnosis of OSA, with additional
concern for patient misclassification if the test returns inconclusive or negative. PSG is
thus recommended in patients with a high clinical suspicion of OSA if HSAT is initially
negative. Nonetheless, the use of HSAT was not demonstrated to provide inferior clinical
benefit compared to PSG when used in the appropriate setting. In adults with comorbid
conditions, PSG is recommended over HSAT due to limited evidence of HSAT validity in
this patient population [48].
The diagnosis of OSA using a split-night protocol has been recommended rather than
a full-night polysomnography protocol. Nevertheless, this recommendation was based
on low-quality evidence. In the context of an appropriate protocol and adequate clinical
and technical expertise, a split-night protocol is considered to have acceptable accuracy in
the diagnosis of OSA and with increased efficiency, cost-effectiveness, and convenience
by diagnosing and establishing therapeutic needs within a single-night protocol. When
completing the diagnostic evaluation, repeat PSG is advised in the setting of a high clinical
suspicion for OSA if the initial PSG returns negative. It is worth mentioning that this recom-
mendation was based on a comparison of single-night PSG to two-night PSG, resulting in
low certainty that repeat PSG would improve outcomes. After this systematic review, there
are areas to improve in the current diagnosis and treatment of OSA, such as more accurate
and cost-effective diagnostic devices, risk stratification tools, and the use of biomarkers,
particularly when conventional diagnostic tests are not feasible or unavailable [48].

5. Conclusions
The 2017 guidelines on the diagnosis of OSA found that the home sleep apnea test
was overall less sensitive and accurate when compared to PSG. PSG is recommended
when there is a negative, inadequate, or inconclusive HSAT and in patients with comorbid
conditions since there is limited evidence of HSAT in this population. Limitations of the
guidelines include the use of older research studies that have used different diagnostic tests
with different devices and cutoffs, as well as the lack of gender and ethnic diversity in the
available literature.
At present, there are still multiple areas that warrant further research to support
clinicians in the diagnostic and decision-making process to improve patient outcomes.
Areas of interest include exploring screening tools to additionally evaluate comorbid
conditions (such as the NoSAS tool) and to fast-track the evaluation of OSA (such as
the presence of morning dry mouth). Utilizing biomarkers such as adiponectin, claudin,
sclerostin, leukocyte cell-derived chemotaxis-2, and the neutrophil-to-lymphocyte ratio can
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 9 of 11

help with the current diagnosis and monitoring of OSA. Measurements of tongue thickness,
stiffness, strength, diaphragmatic thickness and contractility, and breath volume when
exposed to small negative pressure can correlate with OSA severity. Incorporating the
parameter of the hypoxic burden in current PSG reports can further help predict major
cardiovascular events. Advancing wearable technology, including acoustic-based devices,
is more accessible, cost-effective, and comfortable for home sleep testing.
Though PAP therapy will likely remain the gold standard in the treatment of OSA,
there is promising research in weight-loss medications to reduce AHI and advances in
implantable hypoglossal nerve stimulator therapy for patients who are intolerant to PAP
therapy. Supportive orofacial myofunctional exercises seem to be effective for treating
patients with mild OSA who do not desire CPAP therapy.

Funding: This research received no external funding.

Data Availability Statement: No new data were created or analyzed in this study. Data sharing is
not applicable to this article.
Conflicts of Interest: The authors declare no conflict of interest.

Abbreviation

AP Adiponectin.
AHI Apnea hypopnea index.
BPAP Bilevel positive airway pressure.
BBB Blood–brain barrier.
BMI Body mass index.
CLDN Claudin.
CVD Cardiovascular disease.
COPD Chronic obstructive pulmonary disease.
CBC Complete blood count.
CPAP Continuous positive airway pressure.
DISE Drug-induced sleep endoscopy.
EEG Electroencephalogram.
EKG Electrocardiogram.
EMG Electromyography.
EOG Electrooculography.
ESS Epworth sleepiness scale.
GERD Gastroesophageal reflux disease.
GLP-1 Glucagon-like peptide-1 receptor.
GIP Glucose-dependent insulinotropic polypeptide.
HGNS Hypoglossal nerve stimulator.
HSAT Home sleep apnea test.
LECT2 Leukocyte cell-derived chemotaxis-2.
MAD Mandibular advancement device.
NLR Neutrophil-to-lymphocyte ratio.
OSA Obstructive sleep apnea.
OMT Orofacial myofunctional therapy.
ODI Oxygen desaturation index.
PLMD Periodic limb movement disorder.
PAT Peripheral arterial tonometery.
PPG Photoplethysmography.
PAP Positive airway pressure.
PSG Polysomnography.
RDI Respiratory disturbance index.
RERA Respiratory-effort-related sleep arousal.
RIP Respiratory inductance plethysmography.
TMD Temporomandibular joint disorder.
J. Otorhinolaryngol. Hear. Balance Med. 2024, 5, 16 10 of 11

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