Prim Care Clin Office Pract

32 (2005) 329–359

Obstructive Sleep Apnea-Hypopnea

Syndrome
Eric J. Olson, MD*, John G. Park, MD,
Timothy I. Morgenthaler, MD
Mayo Clinic College of Medicine, Division of Pulmonary and Critical Care Medicine,
Mayo Sleep Disorders Center, 200 1st Street SW, Rochester, MN 55905, USA

The explosive growth in sleep medicine has been fueled by an ever-

increasing appreciation of the obstructive sleep apnea-hypopnea syndrome
(OSAHS), a condition of symptomatic, repetitive episodes of airflow
reduction caused by upper airway collapse during sleep. Although the
original polysomnographic description was 40 years ago [1], interest in
OSAHS did not accelerate until the introduction of continuous positive
airway pressure (CPAP) in 1981 [2]. Greater appreciation of the
cardiovascular consequences of OSAHS [3], combined with the increasing
prevalence of obesity [4], has resulted in a tremendous demand for sleep
medicine services which remains incompletely addressed despite an
approximately 300% increase in board-certified sleep medicine specialists
and accredited sleep facilities in the United States over the past decade. This
review of the terminology, clinical consequences, pathophysiology, epide-
miology, diagnosis, and treatment of OSAHS is aimed at the primary care
provider who plays a crucial role in case recognition, patient/partner
education, and treatment monitoring. Several excellent reviews of OSAHS
have recently been published [5–7].

Terminology
Snoring is a repetitive sound caused by vibration of upper airway
structures during sleep. The intermediate collapsibility of the nonapneics’
upper airway relative to normals and OSAHS patients [8] has led to the
concept that snoring and OSAHS are part of a spectrum of sleep-related

* Corresponding author.
E-mail address: olson.eric@mayo.edu (E.J. Olson).

0095-4543/05/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.pop.2005.02.007 primarycare.theclinics.com
330 OLSON et al

breathing disorders. Lying within this continuum are respiratory effort-

related arousals (RERAs). An RERA is a series of breaths occurring over at
least 10 seconds associated with ever-increasing respiratory effort against
a narrowed upper airway that terminates with an arousal before criteria for
an apnea or hypopnea are met [9]. With esophageal pressure monitoring,
RERAs are marked by progressively negative esophageal pressure
deflections (reflecting increasing work of breathing) during the breaths
immediately preceding an arousal. Loud snoring often, but not invariably,
accompanies RERAs. Upper airway resistance syndrome (UARS) has been
used to describe the condition of excessive sleepiness associated with ten or
more RERAs per hour [10].
Obstructive apneas and hypopneas are abnormal events characterized by
at least 10-second reductions in ventilation during sleep that occur when
ongoing respiratory efforts are insufficient in the face of upper airway
narrowing [9]. They differ only in the extent to which breathing is limited;
apneas are marked by cessation of ventilation and hypopneas by partial
diminution of airflow. Oxygen desaturation and arousal at termination
usually accompany these events. The specifics of the hypopnea definition
have varied over time. At present, the Clinical Practice Review Committee
of the American Academy of Sleep Medicine (AASM) [11] and the Centers
for Medicare and Medicaid Services (CMS) define hypopnea as at least
a 30% reduction in airflow for 10 seconds or longer together with at least
a 4% oxygen desaturation.
Precise distinction between apneas and hypopneas is not crucial because
they are considered to have shared pathophysiology, clinical significance,
and treatment [9]. Accordingly, OSAHS has been traditionally classified by
the apnea–hypopnea index (AHI), which is the polysomnographically-
derived number of apneas and hypopneas per hour of sleep. A similar but
not necessarily equivalent term is the respiratory disturbance index (RDI).
The RDI may be used to report the number of apneas and hypopneas per
hour of recording in limited portable study devices that do not measure
sleep, or the RDI may refer to the number of apneas, hypopneas, and
RERAs per hour. By consensus, OSAHS is diagnosed in patients who have
an AHI greater than or equal to five along with daytime dysfunction [9],
or who have an AHI greater than or equal to 15. An AASM expert panel
has recommended that, at least for purposes of standardizing research
methodology, OSAHS be defined as mild with an AHI of 5 to 14, moderate
with an AHI of 15 to 30, and severe with an AHI greater than 30 (where
AHI includes apneas, hypopneas, and RERAs) [9]. The threshold of five
events per hour is based on epidemiologic data revealing increased risk for
adverse outcomes, such as hypertension [12,13] and motor vehicle accidents
[14], in subjects who have an AHI greater than five. This threshold is backed
by intervention data demonstrating subjective and functional improvements
in treated patients who have AHIs of 5 to 15 [15]. Although the AHI may
not be the most accurate encapsulation of the acute and chronic physiologic
 OSAHS 331

consequences of OSAHS, [16,17], it remains for now the most pragmatic

summary statistic for the disorder.
Obesity hypoventilation syndrome (OHS) refers to hypercapnia in the
setting of medically complicated obesity. Its extreme manifestation is
Pickwickian syndrome, a term coined by Burwell et al [18] to describe the
constellation of super obesity, edema, plethora, polycythemia, and cor
pulmonale. OHS is caused by a combination of impaired central respiratory
control, respiratory muscle dysfunction in the face of increased load, and
OSAHS, although the relative contributions of each are difficult to assign
[19]. Most patients who have OHS have some degree of OSAHS [20]. The
AASM has proposed use of the term sleep hypoventilation syndrome to
encompass OHS and other conditions of sleep hypoventilation not strictly
caused by apneas and hypopneas [9].

Pathophysiology
The upper airway is a complex structure that is an integral component of
breathing, vocal expression, and swallowing. It is not a simple rigid tube,
but rather a dynamic conduit whose functional organization is extremely
challenging to characterize [21]. During normal awake respiration, the
collapsing tendency of the negative inspiratory pressure within the upper
airway lumen is balanced by the outward force of pharyngeal dilator muscle
activity under central nervous system control [22,23]. The understanding of
why apneas and hypopneas occur during sleep remains incomplete. At
present, pathologic upper airway narrowing is believed to occur when
normal sleep-induced changes in upper airway physiology, such as reduction
of tonic pharyngeal musculature activity and loss of compensatory reflex
dilator mechanisms, result in insufficient ability to maintain airway stability
in the context of an anatomically or functionally vulnerable pharynx [24].
The upper airway anatomic variables pertinent to OSAHS vulnerability
include size, configuration, and length. Different imaging techniques [21,24]
have revealed that patients who have OSAHS generally have smaller upper
airways than nonapneics because of increased parapharyngeal fat, tongue
prominence, elongated palate, or, perhaps most importantly, thickened
lateral pharyngeal walls [25,26]. The thickened lateral pharyngeal walls in
OSAHS patients explains why the major axis of apneics’ upper airways may
be directed anteroposteriorly, potentially placing the pharyngeal dilator
muscles at a mechanical disadvantage [29], as opposed to the normal lateral
orientation [27,28]. On physical examination of a series of patients referred
for polysomnography, the finding of lateral pharyngeal wall encroachment
by the peritonsillar pillars was associated with the highest risk for OSAHS
[30]. Greater pharyngeal length increases collapsibility and may explain, in
part, why men may be more susceptible to OSAHS than women [31].
Certain risk factors may interrelate with anatomic upper airway pre-
disposition and sleep-induced neuromuscular attenuation in the pathogenesis
332 OLSON et al

of OSAHS. Identification of these risk factors may help the primary care
physician with OSAHS case detection.

Overweight and obesity

Greater-than-ideal weight is clearly a strong risk factor for OSAHS. In
the Wisconsin Sleep Cohort, an ongoing study of middle-age state
employees undergoing serial polysomnography, a 1 standard deviation
increase in body mass index (BMI) was associated with a 4.5-fold increased
risk for OSAHS [32]. Furthermore, a 10% weight gain in subjects who had
an AHI less than or equal to 15 at baseline was associated with a sixfold
greater risk for developing an AHI greater than 15 at 4-year follow-up
versus those who had stable weight [33]. Obesity may compromise
pharyngeal patency through increased extraluminal fat deposition, alter-
ation of upper airway muscle functional relationships, or reduction of the
functional residual capacity with decreased caudal, stabilizing traction
(‘‘tracheal tug’’) on the upper airway [24,34]. The body fat distribution is
also important; visceral and truncal fat accumulation (tendency toward
central obesity) and neck circumference measures are more tightly
correlated with the AHI than BMI alone [35].

Smoking
Smoking may increase OSAHS through upper airway inflammation and
edema or sleep instability from nicotine withdrawal (apneas and hypopneas
may be more common during lighter stages of sleep) [16]. Smokers were
three times more likely to have OSAHS than nonsmokers in the Wisconsin
Sleep Cohort [36].

Nasal congestion
The nose produces two thirds of total airway resistance [37]. Further
reductions in nasal cross-sectional area by allergic, infectious, or chronic
nonallergic (idiopathic) rhinitis or mechanical obstruction predispose to
upper airway collapse by amplifying the pressure differential between the
atmosphere and the thoracic cavity, resulting in greater flow turbulence in
the pharynx, or by promoting oral breathing, which may decrease nasal
receptor-derived stimulation of ventilation and alter phasic activity of upper
airway muscles [38]. Nighttime nasal congestion was associated with a 1.8
odds ratio for an AHI greater than five versus no congestion in the
Wisconsin Sleep Cohort [39].

Others
Anesthesia [40], sedative/hypnotics [41], and sleep deprivation [42] can
further diminish pharyngeal dilator activity. The retro positioning of the
tongue and soft palate by gravitational effects during supine (ie, on the
 OSAHS 333

back) sleep further reduces upper airway area [43]. In the short-term,
alcohol before bedtime can increase sleep-disordered breathing events [44],
but the effect of long-term alcohol ingestion on OSAHS risk is not clear [16].
Clinically significant upper airway narrowing most commonly occurs
behind the uvula and soft palate (velopharynx), behind the tongue, or at
both sites. With obstruction comes increasing ventilatory effort and possible
arousal (RERA). With advanced obstruction, hypopneas or apneas develop
with resultant hypercapnia and hypoxia from insufficient ventilation. These
chemostimuli may spur progressive increases in ventilatory effort to the
point of arousal. Airway patency and effective ventilation are temporarily
restored. Although the role of arousals in resumption of airway patency has
long been thought to be important to restoring (at least transiently)
ventilation homeostasis, this may be an overly simplistic view. Many apneas
and hypopneas are terminated in the absence of detectable arousals, and
recent work suggests that arousals may actually contribute to the severity of
OSAHS by promoting airflow overshoot, thereby increasing respiratory
control instability [45].

Consequences of obstructive sleep apnea-hypopnea syndrome

There are several personal and public health consequences of OSAHS.
Untreated OSAHS patients have higher health care use rates and incur
greater medical costs [46].

Neurobehavioral and social

Features of OSAHS include excessive daytime sleepiness, impaired
vigilance, mood disturbances, and cognitive dysfunction [47]. Consequently,
the pretreatment personal and public health ramifications include increased
risk for motor vehicle accidents, occupational injuries, and decreased quality
of life [16]. The odds ratio for involvement in automotive collisions for
drivers who have OSAHS versus those who do not is 2.5 [48]. An estimated
800,000 people were involved in OSAHS-related motor vehicle accidents
in the United States in 2000 at a cost of $15.9 billion and 1400 lives [48].
Impairment by neuropsychologic testing is demonstrable with even mild
OSAHS. With an AHI of 15, the decrement is equivalent to that associated
with 5 years of aging [49]. Vulnerability to sleepiness resulting from OSAHS
varies significantly between patients. Partners of OSAHS patients suffer
from poor sleep [50], which subjectively improves following OSAHS
treatment [51,52].

Cardiac and vascular

The repetitive hypoxemia, hypercapnia, negative intrathoracic pressure
swings, and arousals characteristic of OSAHS acutely disrupt cardiovascular
334 OLSON et al

relaxation during sleep [3,53]. Sympathetic nervous system activity increases

through chemoreflex mechanisms during the apnea/hypopnea and rises
further with arousal at event termination, resulting in often-dramatic surges
in heart rate and blood pressure [54]. Negative intrathoracic pressures as
a result of ineffective efforts to breathe against an occluded upper airway
further increase left ventricular (LV) afterload by amplifying the LV
transmural pressure (ie, the difference between the intracardiac and
intrathoracic pressure) [55], and impair LV relaxation and filling [56].
Increased LV afterload and decreased LV preload cause reductions in
cardiac output just as oxyhemoglobin saturation is decreasing. Over time, the
countless episodes of hypoxemia/reoxygenation, pressor swells, and sympa-
thetic activation may lead to vascular endothelial dysfunction, increases in
inflammatory mediators, and hypercoagulation, all of which have been
demonstrated in OSAHS patients [3,57,58].
It is biologically plausible that these acute and chronic abnormalities may
be involved in the development or exacerbation of various cardiovascular
disorders. The Sleep Heart Health Study demonstrated cross-sectional,
dose-dependent associations between OSAHS and vascular disease [59].
More than 6000 subjects from multiple longitudinal cardiovascular cohorts
were studied with in-home polysomnography. For those in the highest
quartile of apnea-hypopnea frequency (11 per hour), the multivariable
adjusted odds of self-reported cardiovascular disease was 1.42 (95% CI,
1.13–1.78), yet definitive causal data are, for the most part, lacking.

Hypertension
Large cross-sectional [12,60,61] and longitudinal [13] studies demonstrate
a dose-dependent link between AHI and hypertension, presumably
mediated by chronically heightened sympathetic activity. For a baseline
AHI greater than 15 in the Wisconsin Sleep Cohort, the odds ratio for
hypertension at 4 years was 2.89 (95% CI, 1.46–5.64) versus zero events per
hour, adjusting for known confounding variables [13]. Hypertension in the
setting of OSAHS may be more difficult to treat. Sleep apnea is listed first in
the table of identifiable causes of hypertension in the ‘‘Seventh Report of
the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure’’ [62]. Recent placebo-controlled trials
have revealed reductions of up to 10 mm Hg in systolic and diastolic
pressures with CPAP [63–65].

Stroke
OSAHS is common in stroke victims who have reported prevalence rates
greater than 50% [66–68]. OSAHS was associated with increased stroke
prevalence in the Sleep Heart Health Study [59]. Putative mechanisms
linking OSAHS and stroke include hypertension, prothrombotic and
proinflammatory changes, and marked increases in intracranial pressure
and decreases in cerebral blood flow during disordered breathing events
 OSAHS 335

[69,70]. Poststroke subjective well-being may be improved by treating

OSAHS with CPAP [71,72]. However, data are insufficient at this time to
conclude that OSAHS is an independent stroke risk factor.

Congestive heart failure

Central, obstructive, or mixed sleep-disordered breathing can occur in the
context of left ventricular dysfunction. The link between OSAHS and
congestive heart failure (CHF) is likely through hypertension. CHF may
reciprocally induce OSAHS. Upper airway edema from elevated central
venous pressure may narrow the pharynx [73]. During the central apneas of
periodic breathing (Cheyne-Stokes respirations), pharyngeal dilator muscle
activity declines which jeopardizes upper airway patency on resumption of
breathing [58]. In the Sleep Heart Health Study, the strongest association
between OSAHS and all cardiac diseases was with CHF [59]. In the highest
AHI quartile (AHI11), the odds ratio for CHF was 2.38 (95% CI, 1.22–
4.62). Treatment of OSAHS with CPAP in the context of CHF improves LV
ejection fraction by 5% to 8% [74,75].

Coronary heart disease

The acute cardiorespiratory derangements characteristic of apneas/
hypopneas may provoke angina in patients who have coronary heart
disease. Chronically, release of vasoactive substances, reactive free oxygen
radicals, proinflammatory cytokines, and adhesion molecules, plus in-
creased platelet aggregability may contribute to the evolution of athero-
sclerosis, but authoritative cause-and-effect data are absent [3].

Cardiac arrhythmias
Hypoxemia-mediated brady- and tachydysrhythmias occur in OSAHS
and are generally reversible with CPAP [76]. Atrial fibrillation is twice as
likely to recur after cardioversion if concurrent OSAHS remains untreated
[77].

Metabolic
The known unfavorable effects of hypoxemia, sleep fragmentation, and
sympathetic activation on glucose regulation provides the basis for the
observed association between OSAHS and impaired glucose tolerance
independent of obesity [78]. This association may serve as another
intermediary mechanism connecting OSAHS and cardiovascular disease
[3]. CPAP modestly improves insulin sensitivity [79]. Additional attention
has been drawn to the role of leptin, an adipocyte-derived factor, which
plays an important role in metabolic and appetite control [80]. Leptin also
influences respiratory control, increases platelet aggregation, and is
proposed as an independent risk factor for vascular disease [3]. Patients
who have OSAHS have elevated leptin levels independent of BMI and
disturbed leptin regulation that is largely corrected by CPAP therapy [35].
336 OLSON et al

Perioperative
Perioperative risk may be higher in OSAHS patients because of difficult
endotracheal intubation, upper airway edema from intubation, forced
supine sleep positioning, and anesthetic agents/narcotic analgesics. Anes-
thetic agents and narcotic analgesics increase upper airway collapsibility,
impair protective arousal mechanisms, and decrease central respiratory
drive [81]. The nature of the risk for nonupper airway surgery is difficult to
quantify. A retrospective study of 101 patients who underwent hip or knee
replacement and who had or were later found to have OSAHS, versus 101
age-, sex-, and operation-matched controls, showed the OSAHS group to
have the higher percentage of patients who experienced complications (39%
in the OSAHS group versus 18% in controls) and longer hospital stays (6.8
 2.8 days versus 5.1  4.1 days) [82].
The AASM Clinical Practice Committee reviewed the literature regarding
perioperative OSAHS management and concluded there were insufficient
data to develop a standard of practice guideline, yet made several general
recommendations to minimize risk [81]. Preoperative evaluation should
routinely include an OSAHS likelihood assessment. If significant OSAHS is
suspected and clinical circumstances allow, surgery should be postponed
until a sleep evaluation is completed. If surgery is urgent/emergent,
suspected OSAHS should prompt careful perioperative use of sedatives/
narcotic analgesics/anxiolytics, appropriate monitoring, and possible use of
empiric CPAP, perhaps with an auto-titrating unit. Patients who have
known OSAHS should perhaps be referred preoperatively to a sleep
specialist for optimization of care if their last recheck was in the distant past.

Others
Many other common conditions encountered by primary care providers
are purportedly linked to OSAHS, including asthma [83,84], gastroesoph-
ageal reflux [85], and erectile dysfunction [86]. Cause and effect relationships
are not established, but inferred from improvements with CPAP. Primary
care providers should keep OSAHS in mind when the aforementioned
medical conditions respond suboptimally to standard therapies.

Epidemiology
The most-cited prevalence figures come from the Wisconsin Sleep Cohort.
Among this group of subjects aged 30 to 60 years, 4% of men and 2% of
women had OSAHS, defined by an AHI greater than or equal to five plus
excessive daytime sleepiness [32]. When considering just the AHI, 24% of
men and 9% of women had an AHI greater than or equal to five, and 9% of
men and 4% of women had an AHI greater than or equal to 15 [32].
Prevalence appears to plateau after age 65 [87]. OSAHS prevalence is similar
 OSAHS 337

or higher in African-Americans compared with Caucasians [88,89]. Although

heightened awareness by primary care providers and the public resulted in
a 12-fold increase in OSAHS diagnosis between 1990 and 1998 [90], 75%
to 80% of cases remain undiagnosed [91]. Underdiagnosis is caused by
a combination of minimal medical school training in sleep medicine,
insufficient awareness among more senior clinicians, patient hesitancy
toward polysomnography, and long delays at sleep medicine facilities.
The sex-related differences in OSAHS prevalence are incompletely
understood. However, cohort data indicating a lessening of gender
prevalence differences after menopause implicates a hormonal basis [92].
In the Wisconsin Sleep Cohort, the adjusted odds ratio for an AHI greater
than or equal to five in postmenopausal women was 2.6 compared with
premenopausal women [93]. Bixler et al [94] demonstrated a fourfold
increased risk for OSAHS in postmenopausal women not taking hormone
replacement therapy (HRT) versus premenopausal women. The gender-
protective effect is diminished by obesity (BMI  32 kg/m2) in pre-
menopausal women and HRT users [94]. Female hormones may influence
OSAHS risk by impacting on upper airway anatomy or neurophysiologic
control [92]. The extent to which underdiagnosis in women contributes to
the prevalence imbalance is not clear. Epidemiologic surveys do not settle
the debate of whether women are equally [95] or less likely [96] to report
classic OSAHS symptoms.

Clinical recognition
History
The history focuses on the frequency and intensity of breathing
disturbances during sleep, unsatisfactory sleep quality, daytime dysfunction,
and OSAHS risk factors [97,98]. Box 1 provides a list of the clinical features
of OSAHS. Questioning should occur ideally in the presence of the bed
partner because they often prompt the evaluation and patients frequently
lack insight or downplay the clinical features. The absence of snoring makes
OSAHS unlikely [99], but the mere presence of snoring lacks specificity for
OSAHS. In the Wisconsin Sleep Cohort, 44% of men and 28% of women
were habitual snorers, yet only one tenth as many had an AHI greater than
five plus daytime sleepiness [32]. Habitual snoring with witnessed apneas
increases diagnostic sensitivity [87].
Similarly, the insidious development of sleepiness in permissive circum-
stances, such as reading, watching television, and audience situations, is well-
known but not specific for OSAHS. Box 2 lists differential diagnoses of
excessive daytime sleepiness. Self-reported daytime hypersomnolence was
found in 21% of men and 26% of women who had an AHI greater than or
equal to five, but also in 12% of men and 28% of women who had an AHI less
than five in a large population-based sample in Spain [100]. The more common
338 OLSON et al

Box 1. Clinical features of obstructive sleep apnea-hypopnea

syndrome: history
Breathing disturbances during sleep
Habitual, socially-disruptive snoring
Witnessed apneas
Gasping or choking
Difficulties maintaining sleep
Snort arousals
Dyspnea spells
Restlessness
Nocturia
Diaphoresis
Gastroesophageal reflux
Daytime dysfunction
Nonrestorative sleep
Excessive daytime sleepiness
Impaired concentration, cognition, or memory
Motor vehicle accidents
Headaches upon arising
Mood lability
Weakened libido
Risk factors
Overweight
Smoking
Nasal congestion
Alcohol
Sedative/hypnotics
Opioid analgesics
Supine (on the back) sleep positioning
Comorbidities
Hypertension
Congestive heart failure
Stroke
Pulmonary hypertension
Diabetes/metabolic syndrome
Postoperative respiratory difficulties

explanation of insufficient sleep time must always be considered. The

headaches associated with OSAHS may occur on awakening and are brief
(\30 minutes) [101]. Nocturia (ie, two or more urination events per night) is
a common but nonspecific feature that worsens with OSAHS severity [102].
 OSAHS 339

Box 2. Differential diagnosis of excessive daytime sleepiness

Too little time in bed
Insufficient sleep syndrome
Impaired sleep quality
Obstructive sleep apnea-hypopnea syndrome
Upper airway resistance syndrome
Central sleep apnea syndrome
Restless legs syndrome/periodic movement disorder
Chronic pain syndromes
Environmental sleep disorder
Intrinsic sleepiness
Narcolepsy
Idiopathic hypersomnia
Periodic hypersomnia
Irregular timing of sleep–wake pattern
Shift work sleep disorder
Delayed/advanced sleep phase syndrome
Time zone change (jet lag) syndrome
Medical/psychiatric comorbidity
Cardiopulmonary disease
Mood disorders
Alcoholism/drug dependence
Medications

Physical examination
The physical examination concentrates on head and neck conditions that
compromise upper airway patency, such as those listed in Box 3. Typical but
nonspecific findings are a low-draping soft palate, elongated uvula,
prominent tongue base, redundant neck tissue, and excess body weight.
The uvula may appear erythematous and edematous as a result of repetitive
vibratory trauma during snoring. The examination can only modestly hone
OSAHS risk determination. Neck circumference over 17 inches has been
highly correlated with OSAHS [30,103]. In a series of 420 patients referred
for polysomnography who had their upper airways examined while in the
supine position during wakefulness, only lateral narrowing of the airway
walls (defined as encroachment of greater than 25% of the pharyngeal space
by peritonsillar tissues, excluding the tonsils) remained an independent risk
factor for OSAHS when controlling for BMI and neck circumference in
men. No upper airway finding achieved predictive significance in women
340 OLSON et al

Box 3. Clinical features of obstructive sleep apnea-hypopnea

syndrome: physical examination
Vitals
Overweight/obesity
Hypertension
General inspection
Somnolence
Craniofacial anomalies
Cushingoid (exogenous or endogenous)
Nose
Septal deviation
Polyps
Turbinate hypertrophy
Mucosal inflammation/edema
Neoplasm
Mouth
Macroglossia
 Down syndrome
 Acromegaly
 Hypothyroidism
 Amyloidosis
Low-hanging soft palate
Elongated/erythematous/edematous uvula
Tonsillar hypertrophy
Overjet (greater than 3-mm anterior–posterior distance between
the upper and lower incisors during occlusion)
Jaw
Retrognathia
Micrognathia
Midface hypoplasia
Neck
Increased circumference
Heart
Pulmonary hypertension
 Increased pulmonic component to the second heart sound
Systemic venous hypertension
 Jugular venous distention
 Pulsatile hepatomegaly
 Edema
 OSAHS 341

[30]. These results underscore the integral role of obesity in OSAHS

pathogenesis. However, the mere presence of overweight (BMI>25 kg/m2)
is not sufficiently discriminatory for OSAHS, as more than two out of every
three adults in the United States are overweight [4], whereas only 1 in 20
adults are estimated to have OSAHS [32].
OSAHS is not considered capable of causing severe increases in right
heart pressures without a comorbid condition producing persistent
hypoxemia [104]. Therefore, severe pulmonary hypertension should prompt
investigation for coexisting disorders. Likewise, OSAHS is an uncommon
singular cause for hypercapnia [20]. Diurnal impaired gas exchange should
prompt consideration of OHS or concurrent chronic obstructive pulmonary
disease.

Laboratory studies
Adjunctive testing may be useful only in selected circumstances. Blood
tests for associated conditions, such as hypothyroidism, should be
performed only when clinical features are suggestive [105] or perhaps in
OSAHS patients who have no obvious predisposing factors [106]. An
arterial blood gas is indicated for suspected OHS. Polycythemia is un-
common, and therefore routine complete blood count is unlikely to serve as
a useful biomarker [107]. Neither upper airway computed tomography nor
MRI have consistently predicted the presence of OSAHS or responses to
surgery and are therefore not routinely indicated. A thorough upper airway
examination with fiberoptic pharyngoscopy by an otorhinolaryngologist is
not diagnostic, but is indicated for patients seeking surgical treatment
options for OSAHS; when input is needed regarding the medical
management of potentially contributory upper airway disorders (eg, chronic
rhinitis); or when the initial head and neck examination reveals an obvious
(eg, tonsillar hypertrophy) or unexplained abnormality.

Prediction formulae
The cardinal manifestations of OSAHS, including snoring, sleepiness,
obesity, and hypertension, are exceedingly common and therefore non-
specific, which makes it challenging for the primary care provider to decide
when to pursue OSAHS. Over 30% of outpatients in a multinational
primary care practice survey had clinical characteristics that suggested
a high probability of OSAHS [108]. Prediction models based on various
combinations of symptoms, demographics, and anthropometric parameters
have been proposed to help clinicians establish OSAHS probability and
prioritize patients for polysomnography [109]. In general, these formulae are
sensitive but not specific, and tested in patients referred to sleep centers, not
primary care settings [110]. As an example, four clinical prediction models
[99,111–113] applied prospectively to a large group referred for OSAHS
342 OLSON et al

evaluation performed equivalently and without distinction (sensitivities

[[75%]; specificities [\55%]; positive predictive values [69%–77%]) [114].
Promising figures have been reported with the Berlin Questionnaire, a survey
that assigns high or low risk for OSAHS on the basis of snoring
characteristics, sleepiness, BMI, and hypertension [115]. When applied in
a multiclinic, primary care setting with portable polysomnography to assess
validity, classification as high risk by the questionnaire predicted a re-
spiratory disturbance index greater than five with a sensitivity of 0.86,
specificity of 0.77, and positive predictive value of 0.89 [115]. The
appropriate clinical application of prediction formulae is not yet fully
defined.

Pulse oximetry
Taking advantage of the repetitive oscillations in the oxyhemoglobin
saturation caused by obstructive apneas and hypopneas, clinicians use pulse
oximetry to screen patients for OSAHS. Published sensitivities and
specificities vary widely because of differences in oximetry interpretation
techniques and study populations [116]. The utility of pulse oximetry is
highest at the extremes of the OSAHS spectrum [117]. When clinical
suspicion is low, a normal study in a patient who has low oxygen stores (eg,
caused by obesity or underlying pulmonary disease) effectively rules out
OSAHS. When clinical suspicion is high, marked saturation instability may
help triage the timing of polysomnography. However, in the case of
intermediate clinical suspicion, abnormal oximetry may also be helpful in
convincing ambivalent patients to consider further evaluation. Pulse
oximetry is not considered a singularly sufficient method to diagnose
OSAHS [118]. RERAs are not detectable by pulse oximetry because
arousals occur before oxyhemoglobin saturation declines. Therefore, sleepy
patients who have normal oximetry require further evaluation.

Summary
The diagnosis of OSAHS is difficult to establish based on history and
physical examination alone. A sleep specialist’s prediction of OSAHS based
solely on clinical features may be correct in only 60% of cases [119]. As
a starting point, OSAHS should be suspected in patients who exhibit loud
habitual snoring, witnessed apneas, increased neck circumference ([17 in),
BMI greater than 30, and hypertension. The prospect that finding and
treating OSAHS in a snorer may improve control of comorbidities, such as
hypertension, CHF, or headaches, may provide additional rationale for
OSAHS suspicion. Pickwickian phenotype is but one subset of OSAHS and
not representative of most OSAHS presentations [91]. Clinical prediction
rules provide a consistent template on which to assess OSAHS risk, may
help avoid further testing in low-suspicion patients, and may expedite
 OSAHS 343

testing for high-risk patients. However, the generalizability of the available

formulae are not clear and the probability data must always be tempered
by clinical judgment. Strong suspicion of OSAHS should be followed by
objective measurement of breathing during sleep using polysomnography.

Polysomnography
Polysomnography is considered the diagnostic ‘‘gold-standard’’ for
OSAHS. It is a laboratory-based, technician-attended recording of sleep
architecture, breathing, and cardiac rhythm through a variety of measure-
ment techniques. Sleep architecture is assessed by electroencephalography,
electro-oculography, and electromyography. Airflow is assessed by oronasal
temperature-sensitive sensors or nasal pressure detectors. Respiratory effort
is assessed by strain gauges, piezo sensors, diaphragmatic electromyography,
or thoracoabdominal inductance plethysmography. Oxyhemoglobin satura-
tion is assessed by pulse oximetry. Cardiac activity is assessed by
electrocardiography. An AASM task force recommends use of inductance
plethysmography and nasal pressure for respiratory monitoring [9]. The
technician usually notes changes in body position and subjectively grades
snoring intensity, although sound sensors are used in some laboratories to
record snoring. Leg electromyography may be added to detect periodic limb
movements of sleep. Esophageal pressure monitoring may supplement
standard respiratory monitoring if RERAs or central sleep apnea are
suspected. Central sleep apnea is distinguished from obstructive apneas by
the absence of esophageal pressure deflections during events signaling
attenuated central respiratory drive.
The reported percentages of patients underdiagnosed after one night of
polysomnography have ranged from 9% [120] to 43% [121]. The more
severe the OSAHS, the greater the night-to-night reproducibility of the AHI
by polysomnography [120]. Le Bon et al [122] reported a diagnostic
sensitivity of 66% for an AHI greater than or equal to five for a full-night
diagnostic polysomnogram in a group of 243 patients who were suspected of
having OSAHS and underwent consecutive-night sleep studies. There was
a 25% increase in sensitivity for an AHI greater than or equal to five after
a second night, when the first night was negative. Therefore, an initially
negative study may not rule out OSAHS, and a second night may be
required if clinical suspicion is strong [123]. Night-to-night differences in
AHI can be caused by variations in sleep position, sleep architecture
(because of a ‘‘first-night effect’’ of sleeping in the laboratory’s novel
environment), nasal congestion, alcohol or drug use, or sleep indebtedness
[98].

Reviewing the polysomnogram results

The polysomnography report can often appear as a daunting array of
numbers. The principal parameter the non–sleep specialist should focus on
344 OLSON et al

is the AHI. Again, abnormal is generally considered an AHI greater than

five with symptoms attributable to sleep disordered breathing, or an AHI
greater than or equal to 15. The AHI specific for sleep position (lateral
decubitus versus supine posture) and sleep stage (non–rapid eye movement
[NREM] versus rapid eye movement [REM]) may be reported separately
because of potential therapeutic implications. Apneas/hypopneas only in the
supine position may be treated simply with sleep position restriction,
whereas REM-only apneas/hypopneas may also be treated conservatively.
Other sleep study parameters beyond the AHI help expand on the extent
of physiologic disruptions caused by OSAHS. The arousal index, defined as
the number of accelerations greater than or equal to 3 seconds in the EEG
pattern that suggests temporary wakefulness per hour of sleep (normal is
less than 15–20 per hour), is increased by apneas, hypopneas, or RERAs.
Common sleep architecture changes include increases in stage 1 NREM
(normal is 5% of sleep) and decreases in stage 3 and 4 NREM (normal is
15%–20% in young adults, and decreases with age) and REM (normal is
20%). The depth of oxyhemoglobin desaturation depends on the length of
the apneas/hypopneas and underlying lung function. Significant ventricular
ectopy in OSAHS is uncommon unless oxyhemoglobin desaturation is
severe or underlying heart disease is present [124].

Modifications of standard polysomnography

Numerous efforts have been made to modify standard polysomnography
to ease the expense, inconvenience, and accessibility. Split-night polysom-
nography, where the initial diagnostic portion is followed on the same night
by a CPAP titration; is well-validated [125]; and does not appear to result in
poorer CPAP compliance [126]. A variety of limited diagnostic monitoring
systems are being used, some designed for unattended home use. The role
for these systems remains contentious. A recent exhaustive review of
portable monitoring for OSAHS conducted jointly by the AASM, American
Thoracic Society, and American College of Chest Physicians [127] led to the
conclusion that there was insufficient evidence to support unattended,
limited, portable monitoring devices for ruling in or ruling out OSAHS
[118]. CMS presently mandates that the diagnosis of OSAHS must be
established by a facility-based (not in the home or mobile facility)
polysomnogram for CPAP reimbursement purposes.

Treatment
OSAHS is a chronic disease that requires patient/partner education about
its ramifications and treatment options, and ongoing follow-up of
management strategies. The decision to treat is based principally on the
desire to improve patients’ well-being, not simply on the AHI [5]. A variety
of options are available, such as those listed in Box 4.
 OSAHS 345

Box 4. Treatment options for obstructive sleep

apnea-hypopnea syndrome
Risk factor modifications
Weight loss
Smoking cessation
Medical or surgical reduction of nasal resistance
Sleep position restriction
Eliminate alcohol consumption before bed
Decrease use of risk factor medications
Positive airway pressure
Standard, fixed CPAP
Auto-titrating CPAP
Bilevel positive airway pressure
Oral appliances
Mandibular advancement devices
Tongue repositioning devices
Surgery
Tracheostomy
Uvulopalatopharyngoplasty
Laser-assisted uvulopalatoplasty
Radiofrequency ablation (uvula, soft palate, tongue base,
turbinates)
Mandibular osteotomy with genioglossus advancement
and hyoid myotomy-suspension
Maxillomandibular advancement
Bariatric surgery

Risk factor modifications

Weight loss, smoking cessation, medical or surgical nasal treatments,
avoiding sleep on the back, and minimizing use of agents that relax the
pharyngeal musculature (eg, alcohol before bedtime) are used as sole
therapies in mild OSAHS and as adjuncts in more severe disease. A 10%
weight loss predicts a 26% decrease in the AHI [33]. The ‘‘t-shirt with tennis
balls,’’ a relatively tight-fitting nightshirt with a pouch containing tennis
balls along the length of the spine, can promote sleep off the back in patients
who have positional OSAHS. There are insufficient data supporting the use
of external nasal dilator strips, internal nasal dilators, or oronasal lubricants
in OSAHS [128]. Nasal-directed therapies alone usually do not cure
OSAHS, but may help decrease CPAP levels [38,129].
346 OLSON et al

Continuous positive airway pressure

CPAP, a device that pneumatically splints the upper airway throughout
the respiratory cycle, is the usual initial treatment for OSAHS [130]. Systems
consist of a bedside blower, a nasal interface, and an intervening flexible 6-
foot hose, all weighing approximately 5 pounds and transportable in a soft-
sided case. Voltage converters are available to accommodate different sleep
environments, such as truck cabs or international venues. The pressure is set
at the level necessary to eliminate snoring, RERAs, and apneas/hypopneas
during conditions of greatest vulnerability (REM sleep in the supine
position) as determined during polysomnography. For most patients, the
prescribed pressure is in the 7 to 11 cm H2O range. CMS provides CPAP
coverage when the AHI is greater than or equal to 15 or is 5 to 14 plus
documented symptoms of excessive sleepiness, impaired cognition, mood
disorders, or insomnia, or documented hypertension, ischemic heart disease,
or history of stroke. Placebo-controlled, randomized trials have demon-
strated the symptomatic [15,131–134] and cardiovascular [63–65,74,75]
benefits of CPAP.

Monitoring and optimizing the continuous positive airway pressure

experience from the perspective of the non–sleep specialist
Follow-up should occur shortly after CPAP initiation and annually
thereafter [130]. The following five questions posed annually or at times of
change in health status provide a basis for the non–sleep specialist to quickly
assess their CPAP patients [97]:
1. What interferes with your use of CPAP?
2. Are you sleepy during the day?
3. Does your bed partner observe snoring or breathing pauses when you
use CPAP?
4. How has your weight changed since CPAP was initially prescribed or
last adjusted?
5. When was the last time your CPAP equipment was checked?
The minimum CPAP requirement is not known, but improvements in
objective daytime sleepiness have been demonstrated even when average use
is less than 4 hours per night [15]. Average use is probably 5 to 6 hours per
night in most compliant patients. Early CPAP-use patterns predict long-
term usage [135,136], highlighting the importance of early support. The
primary care provider, sleep specialist, and CPAP supplier must effectively
collaborate to educate the patient and partner on why the treatment of their
OSAHS is important, how CPAP works, why it was chosen as their
treatment option, and the specific features of their CPAP equipment. Long-
term use also appears to correlate directly with increasing AHI [136].
Compliance rates of 86% have been reported at 3 years [136]. Many units
 OSAHS 347

now come with an internal compliance monitor whose detailed use

information can be downloaded by computer.
Commonly encountered problems with CPAP and suggested options for
the primary care provider are listed in Table 1. The CPAP ramp, auto-
titrating CPAP, or bilevel systems may alleviate difficulties tolerating the

Table 1
Trouble-shooting guide for common continuous positive airway pressure-related problems
Problem Solutions
Difficulty tolerating  Have sleep center or vendor check blower to make sure
pressure pressure is set as prescribed
 Activate CPAP ramp feature
 Wear CPAP while awake (daily practice)
 Lower pressure by 1–2 cm H2O with or without adjunctive
measures (eg. sleep on sides); some degree of OSAHS may
reemerge
 Return to sleep center for consideration of auto-adjusting
CPAP or bilevel positive airway pressure therapy
Mask air leaks  Ensure mask or pillows situated properly
 Return to sleep center or vendor for resizing
 Protective eye covering during sleep
Intolerance of interface  Loosen mask slightly
(discomfort; nasal  Ensure mask or pillows situated properly
skin breakdown)  Rule out interface modification by patient; inspect and replace
interface if worn-out
 Return to sleep center or vendor for resizing or to obtain an
oral interface
 Barrier, such as moleskin or bandage, for bridge of nose
irritation
 Temporary holiday from CPAP
Nasal congestion  Nasal saline spray before starting CPAP
 Add heated CPAP humidifier; ensure patients are cleaning/air
drying humidifier reservoir daily
 Nasal steroid spray
 Ipratropium bromide nasal spray if rhinitis/rhinorrhea
 Have sleep center or vendor fit patient for oronasal mask
or oral interface
Claustrophobic  Have sleep center or vendor check fit of patient’s nasal pillows
response or sleeker mask
 Wear CPAP while awake (daily practice)
 Refer back to sleep center for frequent phone support
or desensitization/relaxation plan
Difficulty initiating  Wear CPAP while awake (daily practice)
sleep with CPAP  Reinforce good sleep hygiene (warm bath before bed; exercise
program; decrease caffeine and alcohol; limit time in bed to 8 h)
 Delay bedtime until very sleepy
 Brief sedative/hypnotic trial
(continued on next page)
348 OLSON et al

Table 1 (continued)
Problem Solutions
Dry mouth  Add CPAP heated humidifier
 Have sleep center or vendor fit patient for oronasal mask
 Add chin strap
Taking off CPAP  Reassure patient that this is common
unintentionally  Assess all other areas of headgear/nasal interface problems,
during sleep especially nasal congestion
 Add humidification
 Add chin strap
 Low pressure alarm on blower unit may awaken patient to
reposition mask
 Severe cases: set alarm at night for patients to check headgear;
progressively set alarm later with improvement
Data from Olson EJ, Moore WR, Morgenthaler TI, et al. Obstructive sleep apnea-hypopnea
syndrome. Mayo Clin Proc 2003;78(12):1545–52.

prescribed pressure. The ramp is a feature on all newer machines that allows
a gradual increase in the pressure from a base of 3 to 4 cm H2O to the
prescribed level over 5 to 45 minutes. This feature can be reset at any time,
but repeated resetting is self-defeating [137]. Auto-titrating CPAP devices
employ algorithms to deliver the appropriate pressure for the given
circumstance within a range of pressures set by the prescriber. These
systems eliminate apneas/hypopneas as effectively as standard CPAP at
slightly lower mean pressures across the night, but produce only modest
increases in compliance [138,139]. Unattended use of auto-titrating devices
for determining a fixed CPAP or to start therapy without polysomnography
by CPAP-naı̈ve patients is not currently established [140]. Experience
suggests some CPAP-intolerant patients will benefit from bilevel positive
airway pressure systems, yet improved compliance has not been demon-
strated by randomized trials [141].
The basic patient interfaces are nasal masks, oronasal masks, and nasal
pillows that come in an assortment of configurations, headgears, and
cushioning materials. Oral interfaces and total face masks are also available.
Nasal skin irritation may occur if the patient is cinching the mask too tightly
in an effort to eliminate air leaks. Nasal mucosal irritation (eg, congestion,
dripping, dryness, sneezing) is the most common problem after initial
acclimatization to CPAP. Heated humidification (integrated into many of
the newer CPAP blower units) and nasal steroids are first-line interventions.
Heated humidification has been shown to improve CPAP compliance
[142,143] and has reduced mouth air leaks [144]. Predictive factors of the
need for heated humidification include age greater than 60, chronic nasal
mucosal diseases, use of nasal drying medications, and previous uvulopa-
latopharyngoplasty (UPPP) [143]. The humidifier reservoir must be emptied
and air-dried daily, then refilled with fresh water at bedtime.
 OSAHS 349

Excessive sleepiness that persists despite ostensibly adequate CPAP

compliance calls for reassessment of the patient. The differential diagnosis
for persistent sleepiness while on CPAP includes technical problems (eg,
incorrect use of mask, pressure incorrectly set by vendor or improperly
altered by patient); inadequate determination of pressure during the initial
sleep study; invalidation of prescribed pressure by patient weight gain or
increases in alcohol/sedative/narcotic use; overestimated CPAP use; or
a concurrent sleep disorder.
Breakthrough snoring indicates that upper airway obstruction is not fully
relieved and that the CPAP level needs upward adjustment, the nasal
interface needs replacement, or the interface may not be situated properly
during sleep. The blower should be checked at least annually and the nasal
interface should be checked or replaced every 6 months.
Changes in the patient’s weight or medical condition may require
alteration in the treatment plan. Management options in response to weight
gain include overnight oximetry with referral to the sleep disorders center if
abnormal, or an empiric increase of 1 to 2 cm H2O if symptoms of OSAHS
have reemerged or oximetry is abnormal.

Oral appliances
Oral appliances (OAs) have been developed to relieve pharyngeal
obstruction by mechanically enlarging or stabilizing the upper airway
through advancement of the mandible or tongue [145]. The mandible is
typically set forward to 50% to 75% of maximal protrusion. Subjective
improvements in snoring are reported in most case series with oral
appliances, where approximately 50% achieve an AHI less than ten, and
patient-reported compliance rates are 75% to 90% [145,146]. Randomized,
crossover comparisons reveal CPAP is more effective at reducing snoring and
lowering the AHI, but OAs are usually preferred by patients [147–150]. Care
must be taken when applying these figures to individual devices because there
are more than 50 commercially available OAs and these figures may not be
applicable to all models. Clinical predictors of positive outcome include
younger age, lower BMI, smaller neck size, positional OSAHS, and lower
AHI [145]. Therefore, OAs are most appropriately used in patients who have
mild to moderate OSAHS, but may also be a salvage option for patients who
have moderate-severe OSAHS and are unable to use CPAP [151].
Adverse effects, including excessive salivation, xerostomia, teeth and gum
discomfort, temporomandibular joint (TMJ) pain, unintended displacement
during sleep, and an altered sense of morning dental occlusion, are common
but usually mild [152]. Contraindications include insufficient teeth to anchor
the device, active dental disease, TMJ disorder, minimal protrusive range,
and childhood age. Close collaboration with the dentist is crucial for proper
patient selection; device fabrication and titration; and monitoring for
possible long-term dental and skeletal changes [151].
350 OLSON et al

Surgery
Surgical interventions offer the promise of freedom from a nightly
therapy, but their impact may be limited because the upper airway
obstruction in OSAHS is often at multiple sites, it is challenging to predict
how patients will respond, and acceptance rates are low for the most
successful procedures (maxillomandibular advancement and tracheostomy).
These procedures may be most effective in patients who have distinct
anatomic abnormalities of the upper airway [6].
The surgical interventions are aimed, sometimes in a sequential manner,
at the suspected sites of obstruction. A convenient paradigm is to classify the
site obstruction as type 1 (retropalatal-predominant); type 2 (retropalatal
and retrolingual); and type 3 (retrolingual only) [153]. Because the
retropalatal region is the major site of narrowing in most cases [154,155],
most OSAHS patients will be type 1 or 2. Palatal-directed procedures for
type 1 and 2 patients include UPPP, laser-assisted uvulopalatoplasty
(LAUP), and radiofrequency ablation (RFA). UPPP modifies the retro-
palatal airway by excision of the uvula, a portion of the soft palate, and
tonsils (if present) under general anesthesia [156]. Less than 50% of patients
achieve an apnea index less than ten and at least a 50% reduction in apneas
with UPPP alone [157]. Acute postoperative pain is pronounced. Potential
long-term adverse effects include velopharyngeal insufficiency (nasal reflux),
voice change, and globus sensation. LAUP is a sequential, office-based
trimming of the uvula and adjacent soft palate typically by carbon dioxide
laser under local anesthesia [158]. Postprocedure pain and complication
rates are similar to UPPP [159]. An AASM review concluded that LAUP
cannot be currently recommended for treatment of OSAHS [160]. RFA is
also a sequential, office-based procedure performed under local anesthesia
in which a handpiece is used to focally apply a temperature-controlled
radiofrequency signal, most commonly to the soft palate, thereby reducing
tissue volume and stiffening the tissues through subsequent fibrosis [161].
Subjective improvements in snoring are to be expected with RFA [162], but
impact on OSAHS is more limited [163]. Pain intensity and duration are less
and complications fewer than with UPPP or LAUP. Adverse effects are
uncommon and primarily limited to mucosal erosion [162]. A variety of
procedures may address retrolingual obstruction for type 2 and 3 patients,
including mandibular osteotomy with genioglossus advancement with hyoid
myotomy-suspension [164].
Assessing the literature for a response rate for so-called ‘‘phase I
procedures’’ (palatal- or tongue-based operations) [165] is difficult because
of slight variations in surgical techniques, nonrandomized patient selection,
and variable intervals before unblinded postoperative polysomnography.
Postoperative AHI less than ten has been reported in 31% [166] to 57%
[167] of patients. Incomplete responders may undergo a phase II procedure
called maxillomandibular advancement in which the maxilla and mandible
 OSAHS 351

are brought forward in unison at least 10 mm. Impressive success rates

([90% with AHI \10 following phase I surgery) have been reported [165–
167]. Surgically induced weight can also lower the AHI [168,169].

Summary
OSAHS should be an expected condition in many patients encountered
by primary care providers. The diagnosis may arise because of patient
daytime dysfunction, partner prompting, or in the course of managing
comorbidities adversely influenced by the hemodynamic, neural, humoral,
and inflammatory consequences of repetitive desaturations and arousals.
OSAHS should be suspected in patients who exhibit habitually loud
snoring, witnessed apneas/choking/gasping during sleep, hypertension, neck
circumferences of 17 inches or greater, obesity, and laterally narrowed
oropharynxes. Diagnosis is established by polysomnography. CPAP is the
treatment of choice for most patients. Education, follow-up, and heated
humidification may help bolster compliance. Lifestyle modifications, oral
appliances, and upper surgeries are additional treatment options.

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