Obstructive Sleep Apnea (OSA)

Back

Practice Essentials

Obstructive sleep apnea (OSA)—also referred to as obstructive sleep apnea-hypopnea—is a sleep disorder that involves cessation or significant decrease in airflow in the presence of breathing effort. It is the most common type of sleep-disordered breathing and is characterized by recurrent episodes of upper airway collapse during sleep.[1] These episodes are associated with recurrent oxyhemoglobin desaturations and arousals from sleep.

OSA that is associated with excessive daytime sleepiness is commonly called obstructive sleep apnea syndrome—also referred to as obstructive sleep apnea-hypopnea syndrome.

The image below illustrates the sleep-related disordered breathing continuum ranging from simple snoring to OSA.



View Image

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occ....

Signs and symptoms

Generally, symptoms of OSA begin insidiously and are often present for years before the patient is referred for evaluation.

Nocturnal symptoms may include the following:

Daytime symptoms may include the following:

See Clinical Presentation for more detail.

Diagnosis

In general, the physical examination is normal in patients with OSA, aside from the presence of obesity (body mass index: >30 kg/m2), an enlarged neck circumference (men: >43 cm [17 in]; women: >37 cm [15 in]), and hypertension.

Evaluate the upper airway in all patients, particularly in nonobese adults with symptoms consistent with OSA.

Examination findings may include the following:

Testing

An overnight sleep study, or polysomnography, is required to diagnose OSA.

Routine laboratory tests, however, are usually not helpful in OSA unless a specific indication is present. Pulmonary function tests are not indicated to make a diagnosis of, or treatment plan for, OSA alone. The standard indications for such testing apply to all patients, with or without OSA.

Obtain a thyrotropin test on any patient with possible OSA who has other signs or symptoms of hypothyroidism, particularly in elderly individuals.

AASM standards and guidelines for diagnostic polysomnography

The American Academy of Sleep Medicine guidelines for the indications and performance of polysomnography include the following[2] :

See Workup for more detail.

Management

Treatment of OSA partly depends on the patients’ severity of sleep-disordered breathing. Those with mild apnea have more options, whereas people with moderate to severe apnea should be treated with nasal continuous positive airway pressure (CPAP).

Conservative therapy and prevention

The following conservative measures may help manage or prevent OSA:

Mechanical measures

Mechanical measures used in the treatment of OSA include the following:

Pharmacotherapy

Medications are generally not a part of the primary treatment recommendations for OSA. However, central nervous system stimulants (eg, modafinil, armodafinil) or solriamfetol (a dopamine/norepinephrine reuptake inhibitor) may be considered for adjunctive use to treat excessive daytime sleepiness in the management of this condition.

Surgery

Surgical intervention for OSA includes, but is not limited to, the following:

See Treatment and Medication for more detail.

Background

Obstructive sleep apnea (OSA)—also referred to as obstructive sleep apnea-hypopnea (OSAH)—is a sleep disorder that involves cessation or significant decrease in airflow in the presence of breathing effort. It is the most common type of sleep-disordered breathing (SDB) and is characterized by recurrent episodes of upper airway (UA) collapse during sleep.[1] These episodes are associated with recurrent oxyhemoglobin desaturations and arousals from sleep.

OSA associated with excessive daytime sleepiness (EDS) is commonly called obstructive sleep apnea syndrome (OSAS)—also referred to as obstructive sleep apnea-hypopnea syndrome (OSAHS). Despite being a common disease, OSAS is underrecognized by most primary care physicians in the United States; an estimated 80% of Americans with OSAS are not diagnosed.[3]

Apnea may occur hundreds of times nightly, 1-2 times per minute, in patients with severe OSA, and it is often accompanied by wide swings in heart rate, a precipitous decrease in oxygen saturation, and brief electroencephalographic (EEG) arousals concomitant with stertorous breathing sounds as a bolus of air is exhaled when the airway reopens.

The cardinal symptoms of sleep apnea include the "3 S ’s": S noring, S leepiness, and S ignificant-other report of sleep apnea episodes. This helpful mnemonic has proven to be valuable in teaching residents to be sensitive in the identification and appropriate referral of these patients for further study.

Also helpful is if patients’ spouses or others who are close to them can attend visits. Often, sleepers are unaware that they have OSA and may in fact regard themselves as "good sleepers" because they "can sleep anytime, anywhere" (eg, in the physician’s waiting room, in traffic, in class, at his or her office). Sleepiness is one of the potentially most morbid symptoms of sleep apnea, owing to the accidents that can occur as a result of it.

OSA is a very important diagnosis for physicians to consider because of its strong association with and potential cause of the most debilitating medical conditions, including hypertension, cardiovascular disease, coronary artery disease, insulin-resistance diabetes, depression, and, as mentioned, sleepiness-related accidents.

Go to Childhood Sleep Apnea for complete information on this topic.

Definitions of respiratory events

For the purposes of the following discussion, it is useful to define the breathing events being examined. These breathing events include the following:

Apnea is defined by the American Academy of Sleep Medicine (AASM) as the cessation of airflow for at least 10 seconds.[4] Apnea may last for 30 seconds or even longer.

The most recent guidelines from the American Academy of Sleep Medicine (AASM Weekly Update 9/26/2013) updated the definitions of the terms for scoring hypopneas (recommended and acceptable), as follows:

An RERA is an event characterized by increasing respiratory effort for 10 seconds or longer leading to an arousal from sleep but one that does not fulfill the criteria for a hypopnea or apnea. The criterion standard to measure RERAs is esophageal manometry, as the AASM recommends. However, esophageal manometry is uncomfortable for patients and impractical to use in most sleep centers.

A reliable and valid way to measure RERAs is with the use of a nasal cannula and pressure transducer. Results obtained with this transducer are reliable. With regard to the diagnosis of OSA, this method does not differ from esophageal manometry in a clinically significant manner. With either method, the respiratory disturbance index (RDI) is greater than 5 and the normal RDI cutoff is greater than 15.

Obstructive apneas and hypopneas are typically distinguished from central events. Obstructive events are characterized by continued thoracoabdominal effort in the setting of partial or complete airflow cessation, central events by lack of thoracoabdominal effort in this setting. Mixed events have both obstructive and central features. They generally begin without thoracoabdominal effort and end with several thoracoabdominal efforts in breathing; they are tabulated in the obstructive apnea index.

Sleep-related breathing disorder continuum

A sleep-related breathing disorder (SRBD) continuum has been described and is supported by research.[5] OSA can be thought of as occupying a range of this continuum.

The idea of the SRBD continuum was first described by Elio Lugaresi: "There is a continuum of intermediate clinical conditions between trivial snoring and the most severe forms of OSAS (which we prefer to call heavy snorers disease). This fact should be taken into consideration for any meaningful approach to the clinical problems posed by snoring. Many issues, however, remain unsettled."[6]

The SRBD continuum suggests that snoring is the initial presenting symptom, and it increases in severity over time and it increases in association with medical disorders that may serve to exacerbate the disorder, such as obesity. Snoring has a constellation of pathophysiological effects.[7]

As the disease progresses, SRBD patients begin to develop increased UA resistance that results in a new hallmark symptom: sleepiness. Sleepiness is caused by increased arousals from sleep.[8] This syndrome has been described as the UA resistance syndrome (UARS). UARS patients are not hypoxic, and hypoxia does not explain why they are sleepy, nor can sleep stage percentages or other polysomnography (PSG) variables. The SRBD continuum predicts that over time, a UARS patient develops OSA, if untreated (see the image below).



View Image

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occ....

OSA has as its hallmark symptoms snoring, sleepiness, spouse apnea report, and hypoxia. The SRBD continuum suggests that over time, untreated OSA may hasten death through heart disease, hypertension, stroke, myocardial infarction, heart failure, cardiac arrhythmia, diabetes, metabolic syndrome, or vehicular or other accident due to sleepiness or other behavioral effects noted.

Pathophysiology

Conceptually, the UA is a compliant tube and, therefore, is subject to collapse.[9] OSA is caused by soft tissue collapse in the pharynx.

Transmural pressure is the difference between intraluminal pressure and the surrounding tissue pressure. If transmural pressure decreases, the cross-sectional area of the pharynx decreases. If this pressure passes a critical point, pharyngeal closing pressure is reached. Exceeding pharyngeal critical pressure (Pcrit) causes a juggernaut of tissues collapsing inward. The airway is obstructed. Until forces change transmural pressure to a net tissue force that is less than Pcrit, the airway remains obstructed. OSA duration is equal to the time that Pcrit is exceeded.

Most patients with OSA demonstrate upper airway obstruction at either the level of the soft palate (ie, nasopharynx) or the level of the tongue (ie, oropharynx). Research indicates that both anatomic and neuromuscular factors are important.

Anatomic factors (eg, enlarged tonsils; volume of the tongue, soft tissue, or lateral pharyngeal walls); length of the soft palate; abnormal positioning of the maxilla and mandible) may each contribute to a decrease in the cross-sectional area of the upper airway and/or increase the pressure surrounding the airway, both of which predispose the airway to collapse.[10, 11] Note that in adults, it is very rare for enlarged tonsils and adenoids to be a cause of OSA. Removing the enlarged adenoids and tonsils alone rarely is an effective surgical remedy; in children, about 80% who have have OSA are cured with the removal of enlarged adenoids and tonsils. There is often a misconception that enlarged adenoids and tonsils may be a singular cause of OSA in both children and adults, but this is not true.

Neuromuscular activity in the UA, including reflex activity, decreases with sleep, and this decrease may be more pronounced in patients with OSA.[12, 13, 14] Reduced ventilatory motor output to upper airway muscles is believed to be the critical initiating event leading to UA obstruction; this effect is most pronounced in patients with a UA predisposed to collapse for anatomical reasons.

Central breathing instability is a well-established factor contributing to the development of central sleep apnea (CSA), particularly in patients with severe congestive heart failure (CHF).[15, 16, 17] Evidence also indicates that central breathing instability contributes to the development of OSAS.

First, evidence of UA obstruction in the absence of ventilatory motor output (central sleep apnea) has been observed.[18] Second, reduction in pharyngeal dilator activity has been associated with periodic breathing[19, 20, 21] and hypocapnia in subjects with evidence of inspiratory flow limitation.[22] Third, men have been shown to be more susceptible to the development of CSA and less responsive to carbon dioxide than women are,[23] a result consistent with the greater prevalence of OSAS in men than in women.

Static and dynamic pathophysiologic factors

Both static factors and dynamic factors are involved in the development of OSA. Static factors include surface adhesive forces, neck and jaw posture, tracheal tug, and gravity. Any anatomic feature that decreases the size of the pharynx (eg, retrognathia) increases the likelihood of OSA. Gravitational forces are felt simply by tilting one’s head back to where the retroposition of the tongue and soft palate reduce the pharyngeal space. For most patients, OSA worsens in the supine sleeping position.

An important static factor that has been found is the reduced diameter of the pharyngeal airway in wakefulness in OSA patients compared with non-OSA patients. In the absence of craniofacial abnormalities, the soft palate, tongue, parapharyngeal fat pads, and lateral pharyngeal walls are enlarged in OSA patients versus non-OSA patients.

Dynamic factors include nasal and pharyngeal airway resistance, the Bernoulli effect, and dynamic adherence.

The Bernoulli effect plays an important dynamic role in OSA pathophysiology. In accordance with this effect, airflow velocity increases at the site of stricture in the airway. As airway velocity increases, pressure on the lateral wall decreases. If the transmural closing pressure is reached, the airway collapses. The Bernoulli effect is exaggerated in areas where the airway is most compliant. Loads on the pharyngeal walls increase adherence and, hence, increase the likelihood of collapse.

This effect helps to partially explain why obese patients, and particularly those with fat deposition in the neck, are most likely to have OSA. Moreover, the cross-sectional area of the airway in patients with OSA is smaller than that of people without OSA; this difference is due to the volume of the soft tissue, including the tongue, lateral pharyngeal walls, soft palate, and parapharyngeal fat pads. In one study, the increased volume of these areas was independent of sex, age, ethnicity, craniofacial size, and fat deposition surrounding the UA.[10]

Given these principles, it is understandable why the likelihood of OSA is increased among obese patients, why weight loss decreases the risk of OSA, and why physical examination helps in predicting the presence of OSA. However, the clinical situation is complex because of the interplay of known static and dynamic factors and because of unknown factors.

Data do not explain why sex, age, and ethnicity are not evenly distributed across epidemiologic studies of OSA patients. (See Epidemiology.) Furthermore, data or physical findings are not helpful for determining with precision who will or will not have OSA and who can or who cannot be cured with UA surgery.

Apnea clusters and oxygen desaturation

OSA often occurs in clusters. An oxygen desaturation occurs with each apnea. The end of the apnea sequence typically ends with a brief (>3 sec) EEG arousal. In patients with severe OSA, the cluster of apneas occurs throughout sleep. The desaturation from the first apnea event is typically associated with a higher desaturation percentage change than subsequent apneas in the series.

An underlying mechanism for how clusters of apneas occur and the rate of oxygen desaturation has been recently studied.[24] The researchers paralyzed lambs and withdrew mechanical ventilation to produce apnea and target oxygen saturation. Once the target was reached and the number of recurrent apneas was met, they stimulated respiration through the ventilator so that oxygen saturation was more than 85%.

The study found that oxygen desaturation was not significantly correlated with resting oxygen saturation, independent of mixed-venous oxygen saturation, using forward stepwise regression modeling. It predicted increased desaturation rates solely based on the size of oxygen reuptake.[24] This occurs when mixed-venous blood with depleted oxygen saturation arrives at the lung in time with the apnea phase.

The rapid change in oxygen desaturation occurred after the second apnea in a series of 10 produced; apneas that followed the second apnea did not have accelerated changes when compared with the second apnea. Isolated apneas did not show rapid changes in oxygen saturation.

The clinical implications of these findings suggest that the reason why continuous positive airway pressure (CPAP) and supplemental oxygen may work to ameliorate rapid desaturation is related to the extent that apneas can remain isolated. This results in a longer ventilatory phase to allow venous reoxygenation.

It should be kept in mind that the events studied were not obstructive events but were apneas associated with hypoxemia. They were not terminated by EEG arousals in a natural way to end an apnea sequence and were not produced in humans. Therefore, this study’s clinical application is associated with several caveats.

Oxidative stress, inflammation, and cardiovascular disease

An excellent review article by Gozal and Kheirandish-Gozal provides a model that attempts to integrate how oxidative stress and inflammatory processes link OSA and cardiovascular disease.[25]

Genetic studies have revealed that the gene that encodes for oxidative stress uniquely contributes toward OSA.[26] This suggests that the development of OSA may be related to inflammation and is not necessarily related to a trigger for oxidative stress, as was previously thought. The gene may play a pivotal role by operating in a positive feedback loop, causing the OSA to begin with and then triggering an inflammatory response that further narrows the UA, exacerbating the OSA.

Etiology

The etiology of OSA involves both structural and nonstructural factors, including genetic factors.

Structural factors

Structural factors related to craniofacial bony anatomy that predispose patients with OSA to pharyngeal collapse during sleep include the following:

Structural factors related to nasal obstruction that predispose patients with OSA to pharyngeal collapse during sleep include polyps, septal deviation, tumors, trauma, and stenosis. Structural factors related to retropalatal obstruction include (1) an elongated, posteriorly placed palate and uvula and (2) tonsil and adenoid hypertrophy (particularly in children). Structural factors related to retroglossal obstruction include macroglossia and tumor.

Studies confirm that craniofacial abnormalities are important in the pathogenesis of OSA, particularly in nonobese patients and children. Moreover, given that different racial groups are inclined to develop OSA at varying degrees of obesity, clinicians should particularly consider the possibility of this disorder in the presence of clinically detectable craniofacial abnormalities.[28, 29]

Previous studies of craniofacial risk factors for OSA have been based predominantly on cephalometry. However, differences in head form (measured by the cranial index) and facial form (measured by the facial index) are considered by anthropologists to provide a basis for structural variation in craniofacial anatomy.

The association of head and facial form with the AHI was assessed in 364 whites and 165 African Americans. Cranial and facial dimensions were measured using anthropometric calipers, and other data collected included the body mass index (BMI), neck circumference, and the AHI.

Cranial index and facial index in whites with OSA (AHI ≥15) differ from those in whites without OSA (AHI < 5). The cranial index was increased and the facial index decreased in subjects with OSA. Cranial and facial indices did not differ in African American subjects based on OSA diagnosis. In whites with OSA, the cranial index was again greater and the facial index was again smaller than in African Americans. The researchers suggested that the cranial index may be useful in phenotyping and identifying population subsets with OSA.[27]

Nonstructural risk factors

Nonstructural risk factors for OSA include the following:

Familial factors also play a role (see below).[30] Families with a high incidence of OSA are reported. Relatives of patients with SDB have a 2- to 4-fold increased risk of SDB compared with control subjects.

Other conditions associated with the development of OSA are as follows:

Hypothyroidism is associated with macroglossia and increased soft tissue mass in the pharyngeal region and thus with an increased risk of SDB. Hypothyroidism is also associated with myopathy that may contribute to UA dysfunction. Although it has been linked with the development of OSA, evidence indicates that its prevalence is no higher in patients with OSA than in the general population. Accordingly, patients with OSA should not be routinely screened for hypothyroidism, except possibly elderly women.

Neurologic syndromes associated with OSA include postpolio syndrome, muscular dystrophies, and autonomic failure syndromes such as Shy-Drager syndrome.

The relationship of OSA to cerebrovascular disease is still being determined. Growing evidence indicates that the prevalence of OSA is increased in patients who have had a stroke. However, whether OSA is a risk factor for stroke or stroke is a risk factor for developing OSA remains unclear.

Like hypothyroidism, acromegaly is associated with macroglossia and increased soft tissue mass in the pharyngeal region and thus with an increased risk of SDB.

Environmental exposures include smoke, environmental irritants or allergens, and alcohol and hypnotic-sedative medications.

Genetic factors

A study examined 52 candidate genes most likely to influence OSA.[26] The study sample included 792 African Americans and 694 European Americans, all older than 18 years. An AHI of 15 or higher was used to define OSA as a clinical entity; the AHI was statistically used as both a continuous and a dichotomous trait. In the African American subjects, 1,080 single nucleotide polymorphisms (SNPs) were genotypes; in the European Americans, 505 SNPs were genotypes. Statistical analysis controlled for adjusted for age, age-squared, and sex, with and without BMI.

The study found the following variants in European Americans: C-reactive protein (CRP) and glial cell line-derived neurotrophic factor (GDNF) were associated with the AHI as both a longitudinal and a dichotomous trait. CRP findings increased the odds ratio for the risk of OSA between 1.45 and 2.87; GDNF increased the odds ratio between 1.53 and 3.89-3.92 for the GDNF gene that looked at risk allele G and GDNF risk allele A, respectively.

The study found the following variant in African Americans with OSA: r9s526240 within serotonin receptor 2a. Risk allele A increased the odds ratio for risk of obstructive sleep apnea from 1.45-2.91 using the reported 95% confidence interval.

CRP appears to mediate inflammation; it is thought to be a marker of inflammation. Such inflammation may increase OSA by increasing mucosal edema and reducing airway caliber.

GDNF influences ventilatory control. It appears to sense oxygen and carbon dioxide at sleep onset transitions, hence playing a role in CSA. GDNF influences the growth of sensory afferent neurons of the carotid body, influencing responses to hypoxia. Its role extends to influencing the growth of neural pathways that are important for normal respiration, specifically at the A5 nucleus of the ventrolateral pons, a critical area that regulates respiratory pattern generation.

The role of 5HT2A includes effects on sleep-wake cycles, importantly influencing rapid eye movement (REM) sleep stage percentage. Medications such as selective serotonin reuptake inhibitors (SSRIs) that occupy 5HT2A receptors reduce or eliminate REM sleep percent time. Other mentioned roles include regulation of upper airway dilator muscle through an excitatory influence on hypoglossal motor output. 5HT2a is involved in appetite regulation, thus playing a role in obesity, a well-known risk factor for obstructive sleep apnea.

The study used rather strict criteria to identify other candidate genes, and less stringent criteria identified other possible candidate genes that may influence the risk of OSA.

Epidemiology

SDB is common in the United States. The National Commission on Sleep Disorders Research estimated that minimal SDB (RDI >5) affects 7-18 million people in the United States and that relatively severe cases (RDI >15) affect 1.8-4 million people. The prevalence increases with age. SDB remains undiagnosed in approximately 92% of affected women and 80% of affected men.

OSA is increasingly prevalent, in both adults and children, in modern society. The estimated prevalence has been 2% for women and 4% for men.[31, 32] Similar data have been found in an epidemiologic study from Pennsylvania.[10, 33] More recent research indicates a prevalence of 4% for women and 9% for men. Data from the Wisconsin Cohort Study indicate that the prevalence of OSA in people aged 30-60 years is 9-24% for men and 4-9% for women.

The prevalence in children is less certain, but the author’s sleep center is seeing increasing numbers of adolescent patients, who are often obese and present similarly to many of their adult counterparts, with the important exception that they may be sleepy and/or hyperactive. A 2007 study has suggested that approximately 6% of adolescents have weekly SDB.[34]

International statistics

The prevalence of OSA in non-American populations has only been studied in men and has been found to be as low as 0.3% (England) and as high as 20-25% (Israel and Australia). The prevalence of OSA in Australian men is estimated to be 3%.

Age distribution for OSA

Aging is an important consideration of risk for OSA. OSA prevalence increases 2-3 times in older persons (>65 y) compared with individuals aged 30-64 years,[35, 36] with an estimated rate as high as 65% in a community sample of people older than 65 years.[37]

After age 65 years, no further relative disparity is noted in the incidence of OSA. One explanation for this plateau is the relative increase in mortality in persons older than 65 years; however, data to support this contention, as attractive as it appears, are insufficient. Scant data are available to help clinicians determine if clinical management should differ between the age cohorts.

Sex distribution for OSA

The male-to-female ratio in community-based studies is 2-3:1.[31, 38] Androgenic patterns of body fat distribution (deposition in the trunk, including the neck area) predispose men to OSA. In general, sex hormones may affect neurologic control of UA-dilating muscles and ventilation.

In population studies that have examined the incidence of OSA, women were not only less likely than men to have OSA but also less likely to be diagnosed early in the disease process. Survival rates are lower for women than for men, after an OSA diagnosis has been established by PSG, presumably due to the delayed OSA diagnosis.

Three large epidemiologic studies have demonstrated that the prevalence of OSA in women appears to increase after menopause.[39, 40, 41] In these studies, women on hormone replacement therapy (HRT) had a prevalence similar to that of premenopausal women. Postmenopausal women are 3 times more likely to have moderate-to-severe OSA compared with premenopausal women. Women who are on HRT are half as likely to have OSA compared with postmenopausal women who are not on HRT.[42]

Premenopausal women with OSAHS tend to be more obese than men with the same severity of disease. Thin women with symptoms of OSAHS appear to have an increased frequency of craniofacial abnormalities.

Evidence indicates that women underreport the symptoms of loud snoring and witnessed apneas, leading to underreferral to sleep centers. This may explain the marked male predominance (male-to-female ratio of approximately 8:1) in sleep center–based studies. Additionally, women have lower AHIs than men, even after correcting for other demographic factors such as BMI and neck circumference.[43, 44, 45]

Prevalence of OSA by race or ethnicity

African American individuals appear to be more predisposed to SDB than white persons. This increased predisposition varies according to age. The odds ratio is greater than 3 in children younger than 13 years and is 1.88 in persons younger than 25 years. In elderly African Americans, the risk is increased 2-fold. Examination of craniofacial morphology found that brachycephaly is associated with an increased AHI in whites but not in African Americans.[27]

Chinese patients with OSA have a more crowded upper airway and relative retrognathia compared with their white counterparts, with statistical controls for BMI and neck circumference.[9] Asians are known to have a shorter cranial base and a more acute cranial base flexure, increasing OSA risk, with BMI and neck circumference being roughly equal. Therefore, interestingly, obesity plays a more prominent role in OSA predisposition in whites than in Chinese persons. This may serve to underscore the role that craniofacial factors have in Chinese patients.

Other populations that may be at increased risk include Mexican Americans and Pacific Islanders.

Prognosis

The short-term prognosis, in relation to symptoms such as daytime sleepiness and snoring, ranges from good to excellent with regular use of CPAP. Several studies, including placebo-controlled studies, have shown significant improvement in measures of cognitive function and general health status (eg, as measured by the Medical Outcome Study Short-Form 36 health survey) after 4-8 weeks of treatment with CPAP. However, studies have not been performed in a large population or for more than a 4- to 8-week treatment period.

The long-term prognosis is unknown because no randomized treatment studies investigating the effect of CPAP on preventing the development of cardiovascular sequelae have been conducted.

Cardiovascular mortality and morbidity

The effect of OSA on mortality has been investigated using observational cohort studies. Marin et al found in a Spanish cohort that severe untreated OSA (AHI >30) is associated with an increased risk of cardiovascular mortality, defined by fatal myocardial infarction (MI) or stroke.[46] Patients with mild OSA or those undergoing treatment with CPAP did not have a significantly increased odds ratio compared with a group of subjects without OSA.[46]

In this study, the authors also found that untreated severe OSA is a significant risk factor for the development of cardiovascular morbidity, which included nonfatal MI and stroke.

Two 2008 population-based studies, one from the United States[47] and one from Australia,[48] also showed increased all-cause mortality in subjects with moderate-to severe OSA. The adjusted hazard ratios in both studies ranged from 3-6.24 for subjects with moderate-to-severe disease compared with no disease.

In the Sleep Heart Health Study,[49] 6441 men and women were followed for a mean of 8.2 years. Increased mortality was observed in patients with OSA, but the effect was primarily observed in men younger than 70 years. Women and men older than 70 years did not have increased mortality. In addition, the increased mortality was seen primarily in patients with the most oxygen desaturation during their sleep.

A 2012 study examined the association between OSA and mortality. Using portable sleep studies with more than 77,000 patients, the authors found that OSA was associated with all-cause mortality in patients younger than 50 years of age. While this is a general conclusion from the study, other variables played a substantial role in mediating this relationship. These data are consistent with earlier data showing that the negative impact of OSA on health is more profound in younger patients.[50]

Campos-Rodriguez et al reported that severe OSA is associated with cardiovascular death in women, and adequate CPAP treatment may reduce this risk.[51] A study in the elderly also suggests that severe OSA not treated with CPAP is associated with an increased risk of cardiovascular death.[52]

Several other studies indicate that CPAP mitigates the increased mortality observed in OSA. In addition to the article from Spain discussed above, a 2005 article[53] suggests that mortality is associated with compliance with CPAP. In a historical cohort of 871 patients, patients who used CPAP more than 6 hours per night had an increased survival rate (96.4%) at 5 years compared with those who used CPAP 1-6 hours per night (91.3%) and less than 1 hour per night (85.5%). Use for more than 6 hours per night was associated with a significantly decreased odds ratio of 0.1.

Patients with a history of ischemic stroke and sleep apnea who regularly used their CPAP device had a decreased mortality compared with those who did not use their CPAP device.[54]

A 2005 study found that OSA was associated with an increased risk of sudden death between the hours of midnight and 6 AM, as compared with the general population (in whom sudden death is more common between 6 AM and noon).[55]

Evidence indicates that OSA is not an independent risk factor for the development of pulmonary hypertension in the absence of other lung disease, as evidenced by the presence of daytime hypoxemia, hypercapnia, or obstructive airway disease.[56]

A study of 150 newly diagnosed patients with OSA by Baguet determined that left ventricular diastolic dysfunction is common in these patients and is related to the severity of oxygen desaturation.[57]

All of the above evidence strongly suggests that OSA is an independent risk factor for the development of cardiovascular disease and death. However, at this time, no definitive randomized studies have investigated the effect of CPAP in preventing the potential cardiovascular risks.

Increased risk of motor vehicle accidents

Many studies have identified a relationship between OSA and motor vehicle accidents. Patients with OSA have been reported to be 2-7 times as likely as control individuals to have a motor vehicle crash; the overall estimated risk was 2.5 in a meta-analysis of 6 studies.[58] Many studies indicate that motor vehicle accidents are more common in patients with severe OSA (generally, AHI >30),[59, 60] but this is not a universal finding.[61]

Methods for predicting if an individual patient will have an automobile accident are not yet sufficiently reliable. Using increasingly refined and realistic driving simulators, Ghosh et al could predict those who failed a driving simulation test compared to those who passed the test. The simulation is a step forward in prediction, but simulation has not yet reached levels that would allow a clinician to determine if an OSA patient is safe to drive a vehicle or not. Though the more severely impaired OSA patients were selected for the study, many of them were able to finish the 50-minute driving simulator without incident. The authors continue to work to refine the simulator. It would be an advance to find a test that is sufficiently reliable for use in the clinical setting.[62]

A study from Australia found that truck drivers with Epworth Sleepiness Scale (ESS) scores higher than 18 had an odds ratio of 2.67 for multiple accidents.[63]

An Internet-linked survey of 35,217 respondents found that subjects who reported at least one near-miss sleepy accident were 1.13 times as likely to have had one actual accident compared with subjects not reporting a near-miss accident.[64] The odds ratio increased to 1.87 for those reporting 4 or more near-miss sleepy accidents. This study indicates that asking patients about near-miss sleepy accidents may be predictive of future accident risk.

Predicting accident risk in patients with OSA is difficult because many individuals with OSA do not accurately perceive their level of drowsiness. No evidence indicates that sleep latency derived from either the multiple sleep latency test (MSLT; a measure of sleep propensity) or the maintenance of wakefulness test (MWT; a measure of wake tendency) are predictive of accident risk.

A large body of work has been compiled on the influence of OSA on driving-simulator performance, with most studies indicating poor performance, similar to that seen with alcohol impairment while driving[65, 66] (though performance may return to normal after treatment). However, whether driving-simulator performance is an accurate predictor of real-world driving is unclear,[67] and no evidence indicates that simulator performance can be used to predict accident risk in OSA patients.[68]

Evidence indicates that CPAP improves driving performance. At least 2 studies have shown improvement on a driving simulator after CPAP use.[69, 70] Specifically, in one study, the number of off-road events decreased from 17.8 to 9 after 1 month of effective CPAP therapy, but no change was noted after a month of ineffective pressure set at 1 cm water.

In addition, 2 studies have looked at the effect of CPAP on actual motor vehicle accident rates. George derived crash rates from Department of Motor Vehicle data for 210 patients with OSA over a 3-year period before and after CPAP therapy; the crash rate was 0.18 while untreated, but fell to 0.06 with treatment.[71] Findley et al reported no further crashes in a group of 36 patients with OSA regularly using CPAP therapy.[72] Thus, evidence suggests that effective treatment of OSA should decrease accident rates.

Despite the elevated risk of crashing, most patients with OSA have not had a crash; therefore, determining which OSA patients are likely to have an accident, which patients should have driving restrictions, and how much benefit would accrue from these restrictions is not clear.[73]

No recent evidence-based guidelines are available regarding driving for the average patient with OSA. The most recent statement on this topic is from 1994.[74]

One approach to this problem outlined in the 1994 statement is the concept of shared responsibilities. Educating the patient about the risks of driving while sleepy or inattentive is the physician’s responsibility. One suggestion is that the patient acknowledges this education by signing a statement to that effect. After receiving proper education, the patient’s responsibilities are to avoid driving while sleepy and, preferably, to refrain from driving until starting treatment for OSA.

Physicians should be referred to their individual state or country motor vehicle departments for local guidelines.

Patient Education

All patients should receive education about sleep and proper sleep hygiene, OSA, and the risks of driving while sleepy. They also should receive education regarding the role of nasal CPAP and the importance of daily use, as well as training in the use of CPAP, from a physician, trained technician, or nurse for at least the first month of therapy. This training promotes long-term adherence with treatment.

For more information, see the Ear, Nose, and Throat Center; Mental Health and Behavior Center; and Sleep Disorders Center, as well as Snoring, Fatigue, Insomnia, Sleep Disorders in Women, and Sleep Disorders and Aging.

History

Obstructive sleep apnea (OSA) symptoms generally begin insidiously and are often present for years before the patient is referred for evaluation.

Nocturnal symptoms may include the following:

Daytime symptoms may include the following:

EDS is one of the most common and difficult symptoms clinicians treat in patients with OSA. It is one of the most debilitating symptoms because it reduces quality of life, impairs daytime performance, and causes neurocognitive deficits (eg, memory deficits).

EDS is most frequently assessed by a sleep physician using the Epworth Sleepiness Scale (ESS). This questionnaire is used to help determine how frequently the patient is likely to doze off in 8 frequently encountered situations.

Although patients do not always accurately describe their sleepiness on this scale compared with objective measures, an ESS score greater than 10 is generally considered sleepy. However, a 2003 study showed that an ESS score of 12 is associated with a greater propensity to fall asleep on the Multiple Sleep Latency Test (MSLT), suggesting that 12 would be a better cutoff.[75]

The ESS score does not correlate well with the primary objective measurement of sleepiness, the MSLT,[76, 77] in that a higher ESS score does not mean shorter latencies on the MSLT. However, a higher ESS score does mean a greater likelihood of falling asleep on the MSLT.[75, 78] The ESS is useful for evaluating responses to treatment; the ESS score should decrease with effective treatment.

Although continuous positive airway pressure (CPAP) treatment quickly reverses EDS in most patients, not all patients use the CPAP device. Moreover, some patients remain sleepy despite effective CPAP treatment. In these patients, modafinil at 200-400 mg/d can effectively enhance alertness without changing CPAP use.[79] Patients with residual excessive sleepiness despite effective CPAP use are an interesting subgroup of patients. The mechanism of EDS in these patients awaits further study.

Most patients who do not report EDS do report being fatigued, having a lack of energy, or being tired during the day. In one study of 190 patients with OSA, patients were more likely to report lack of energy (62%), fatigue (57%), and tiredness (61%) than sleepiness (47%). When asked to choose their most significant symptom, 40% of patients chose lack of energy, compared with 22% for sleepiness.[80]

Partly because of their EDS, patients with OSA have substantially impaired daytime functioning, intellectual capacity, memory, psychomotor vigilance (decreased attention and concentration), and motor coordination. Causes include both sleep fragmentation and hypoxemia due to OSA. It is conceivable that these neurocognitive deficits could be reversed with CPAP. OSA patients showed an overrecruitment of brain regions compared with controls, in the presence of the same level of performance on a working-memory task.[81]

Physical Examination

The general physical examination is frequently normal in patients with OSA, other than the presence of obesity, an enlarged neck circumference, and hypertension. Perform an evaluation of the upper airway in all patients, but particularly in nonobese adults with symptoms consistent with OSA.

Physical examination findings may include the following:

Approximately 30% of patients with a BMI greater than 30 and 50% of those with a BMI greater than 40 have OSA. In the United States, 20% of men and 25% of women have a BMI greater than 30. Unfortunately, obesity has become an epidemic in industrialized nations. One study showed that the number of people with a BMI greater than 40 has tripled since 2000.[82] Patients with obesity hypoventilation syndrome and some patients with OSA may have evidence of pulmonary hypertension and right-side heart failure.

A large neck circumference has been associated with an increased risk of OSA. Neck circumference may correlate with OSA better than BMI. In one study, subjects with OSA had a neck circumference 4 cm larger than subjects without OSA. In addition, neck circumference of 40 cm or greater had a sensitivity of 61% and a specificity of 93% for OSA, regardless of the person’s sex.

The Mallampati score has been used for many years to identify patients at risk for difficult tracheal intubation. The classification provides a score of 1-4 based on the anatomic features of the airway seen when the patient opens his or her mouth and protrudes the tongue (see the image below). A 2006 study showed that for each 1-unit increase in the Mallampati score, the odds ratio of having OSA (defined by an apnea-hypopnea index [AHI] >5) increased by 2.5. In addition, the AHI increased by 5 events per hour.[83]



View Image

The Mallampati Classification is illustrated. The airway class is based on this visual heuristic.



View Image

In this polysomnogram summary graph, obstructive sleep apnea (OSA) severity and the degree of oxygen desaturation (SpO2%) worsen in rapid eye movement....

Predictive Value of History and Physical Examination

The predictive value of initial clinical evaluation for OSA can be based on the following:

Questioning patients and others is necessary, as follows:

Sex-related differences include the following:

The mnemonic STOP is helpful and includes the following:

If the patient answers yes to more than 2 questions, the sensitivity of him or her having an AHI greater than 5 is 66% and the sensitivity of him or her having an AHI greater than 15 is 74%.

The mnemonic BANG is also useful, as follows:

If the criteria from both the STOP and BANG mnemonics are met, the sensitivity of the patient having an AHI of greater than 5 is 93% and an AHI of greater than 15 is 83%.[84]

Research has shown that the STOP-Bang questionnaire is both simple to use for busy clinicians and predictive of OSA. A 2012 study supports existing research indicating that screening in presurgical patients using the STOP-Bang score has a high probability of OSA detection.[85] Not all patient populations can be identified to the same degree of accuracy with the same tool, therefore research continues to find the best predictors for various patient populations.

Ramachandran et al have developed and validated a clinical score for predicting the diagnosis of OSA preoperatively in a general surgical population.[86] Their perioperative sleep apnea prediction (P-SAP) score is based on 3 demographic variables (age >43 y, male sex, and obesity), 3 history variables (history of snoring, diabetes mellitus type 2, and hypertension), and 3 airway measures (thick neck, modified Mallampati class 3 or 4, and reduced thyromental distance).

A diagnostic threshold P-SAP score of 2 or higher showed excellent sensitivity (0.939) but poor specificity (0.323), whereas a P-SAP score of 6 or higher had poor sensitivity (0.239) but excellent specificity (0.911).[86]

Cardiovascular Disease in Obstructive Sleep Apnea

A scientific statement was published by the American Heart Association and the American College of Cardiology Foundation on August 25, 2008. This expert review examined OSA and cardiovascular disease. The results are paraphrased below.[87]

The possible mechanisms through which OSA may lead to cardiovascular disease were examined. OSA patients often have hypoxemia, reoxygenation, sleep arousals, less sleep time than healthy individuals, elevated negative intrathoracic pressure, and, in some individuals, hypercapnia.

The commonly accepted contributions of these OSA-related pathophysiological factors may affect sympathetic activation, metabolic dysregulation, left atrial enlargement, endothelial dysfunction, systemic inflammation, and hypercoagulability. These mechanisms can lead to hypertension (both systemic and pulmonary), heart failure, cardiac arrhythmias, renal disease, stroke and myocardial infarction, and sudden death in sleep.

A review by Somers et al yielded 2 particularly significant findings.[87] First, the data suggest that evaluation and treatment for OSA are not recommended in every patient with cardiac disease, but the threshold for a referral for polysomnography (PSG) and for treatment of OSA should be low. Second, because OSA affects younger individuals with cardiovascular disease to a greater extent than older individuals with cardiovascular disease, this threshold for OSA evaluation and treatment should be even lower.

Hypertension

Systemic hypertension is observed in 50-70% of patients with OSA. Several large cross-sectional studies have demonstrated that OSA is a risk factor for developing hypertension, independent of obesity, age, alcohol intake, and smoking.[39, 88]

More recently, subjects in the Wisconsin Cohort Study were prospectively monitored for the development of hypertension. The investigators found a dose-response relationship between the degree of OSA and the presence of hypertension 4 years later (odds ratio of 2.03 for an AHI of 5-15 and 2.89 for an AHI >15), independent of confounding variables.[89]

In the Sleep Heart Study,[90] 2470 subjects without OSA were followed for 5 years for the development of hypertension. In this cohort, the AHI was not an independent predictor of hypertension. Differences between the 2 study populations and differences in measurement of SDB events likely explain the discrepant results.

Treatment has been shown to decrease both systolic and diastolic hypertension. CPAP treatment has been shown to have moderate and variable effects on blood pressure (BP) in OSA patients.[91, 92, 93] However, no conclusive study has demonstrated that treating OSA with nasal CPAP lowers the blood pressure on a long-term basis.

CPAP has been investigated in nonsleepy hypertensive OSA patients. CPAP treatment for 1 year was associated with decreases in both systolic and diastolic BP. This effect was only evident in patients who used their CPAP device for more than 5.6 hours per night.[94]

Patients with hypertension and OSA may require CPAP and antihypertensive medication. A study examining the use of valsartan (160 mg/d) and CPAP in patients with newly diagnosed hypertension and newly diagnosed OSA found that together, the treatments synergistically reduced BP.[95] .Because OSA patients use CPAP regardless of whether they are taking medication for hypertension, the success of the CPAP-valsartan combination was the most important clinically relevant finding.

Decreased CPAP use was associated with higher nighttime systolic BP. Office BP, reported as entry criteria, was not reported after treatments in the results. Systolic and diastolic BP were not within normal limits on every time period measured.

Because of the reported negative correlations with CPAP use and nocturnal systolic BP as a function of the duration of CPAP use, an intervention to augment CPAP use would likely have been helpful to adequately assess CPAP’s effect on BP alone; the time spent on CPAP during this study was perhaps too low to demonstrate a larger change in BP parameters.

Although, as noted (see above), other studies suggest that the ability of CPAP to reduce hypertension require 5.6 hours of use per night, the subjects in this study used CPAP approximately 5 hours per night. Again, this limits the effect of CPAP on hypertension as a treatment alone and in combination with valsartan. On other hand, BP reductions with fewer hours of CPAP use than previous published studies further supports CPAP’s robust effect on BP and that fewer than 5.6 hours of CPAP use can lead to BP reductions.

Antihypertensive drug treatment does not improve OSA; however, clonidine, which is an REM sleep suppressant, may improve OSA indirectly by reducing the patient’s percentage of REM sleep because the REM sleep is when OSA is most severe. Finally, angiotensin-converting enzyme (ACE) inhibitor use may worsen OSA because of the adverse effects of cough and rhinopharyngeal inflammation, 2 effects that cease with discontinuation of the drug.

Atherosclerosis

OSA has been linked with the development of atherosclerosis. In a study of 36 subjects[96] with OSA and 16 matched controls, all without comorbidities, subjects with moderate-to-severe OSA were found to have increased carotid intima media thickness, increased pulse wave velocity, and increased carotid diameter, all of which are consistent with atherosclerosis. Abnormalities in these parameters were predicted by either the AHI or the degree of nocturnal desaturation. A 2007 follow-up study showed regression of these abnormalities after nasal CPAP.[97]

Congestive heart failure

OSA has not been established as a cause of heart failure, and whether it hastens death in patients with heart failure is uncertain. However, a 2007 study examining untreated OSA in patients with heart failure reported that those with an AHI higher than 15 had increased mortality compared with those with an AHI below 15.[98] CPAP treatment in patients with OSA and heart failure may reduce mortality,[99] but the evidence is less than absolute because no randomized clinical trials have tested the effects.

A study by Javaheri et al examined a study population of 30,719 patients with heart failure. Only 1,263 (4%) were suspected of having OSA.[100] After adjustments for age, sex, and comorbidities, patients with heart failure who were diagnosed with OSA and received treatment had a better 2-year survival rate than those who were not treated.

OSA patients with heart failure may be less likely to report daytime sleepiness, as measured by the Epworth Sleepiness Scale, compared to those OSA patients without HF. The authors of one study propose this is likely due to central adrenergic alerting mechanisms, as alertness is incompatible with sleep and may serve to mask subjective sleepiness.[101]

Cardiac arrhythmias

Patients with severe SDB have a 2- to 4-fold increased risk of experiencing nocturnal complex arrhythmia. Bradyarrhythmia is more common in OSA patients (occurring in approximately 10% of OSA patients), especially during REM sleep state and when a greater than 4% drop in oxygen saturation occurs. Additionally, atrioventricular block and asystole may occur in the absence of conduction disease.

Premature ventricular contractions (PVCs) also are much more common in patients who have OSA than in those who do not (66% vs 0-12%), and they are most likely to occur during an apnea; however, CPAP treatment reduces the frequency of the PVCs (by up to 58%, according to one study).

In a study of SDB and nocturnal cardiac arrhythmias in older men, Mehra et al found that the likelihood of atrial fibrillation (AF) or complex ventricular ectopy increased along with the severity of SDB. In addition, different forms of SDB were associated with the different types of arrhythmias. PSG in 2911 participants showed that the odds of AF and of complex ventricular ectopy increased with increasing quartiles of the RDI (a major index including all apneas and hypopneas).[102]

Myocardial ischemia and infarction

OSA patients have double the prevalence of coronary artery disease (CAD), and an independent association has been shown between OSA and subclinical CAD, as demonstrated by coronary artery calcification. Further, OSA apparently affects the timing of sudden cardiac death: research shows that more than 50% of the sudden cardiac deaths that occur in OSA patients do so between 10 PM and 6 AM, whereas the more common time for sudden cardiac death is from 6-11 AM.

Men with untreated OSA and an AHI of greater than 30 had an increased number of fatal and nonfatal cardiovascular events, but treated OSA patients have a number of events similar to snorers who do not have OSA.

Stroke

The Sleep Heart Health Study[103] showed that OSA had a stronger relationship with stroke than with any other cardiovascular disease.

Patients who have OSA are more likely to have a stroke and die than people who do not. This correlation persists even if researchers control for the risk factors of age, sex, race, smoking, alcohol consumption, BMI, diabetes mellitus, hyperlipidemia, AF, and hypertension.

Time-to-event analyses have shown that patients with OSA (who were undergoing weight loss, CPAP treatment, or surgery) have an increased hazard ratio for stroke or death of 1.97. The risk of stroke or death was most severe in the quartile of patients with the most severe AHI. The hazard ratio increased to 3.30 when the AHI was greater than 36. This study was not powered sufficiently to determine if obstructive sleep apnea treatment affects survival.

A number of prospective observational cohort studies have investigated the relationship between OSA and stroke. In the Wisconsin Cohort Study, an AHI of greater than 20 was associated with an increased risk of stroke over a 4-year follow-up (odds ratio, 4.31), although the odds ratio lost significance when corrected for age, BMI, and sex.[104]

In a study from Yale, after a mean follow-up of 3.4 years, an AHI of greater than 5 was associated with increased risk of stroke after adjustment for multiple confounders (hazard ratio, 1.97).[105]

In a group of elderly subjects followed over 6 years, patients with severe OSA (AHI >30/h) had an increased risk of stroke.[106] These studies provide evidence that OSA is a risk factor for the development of stroke.

Metabolic syndrome

OSA has an association with the metabolic syndrome. The metabolic syndrome is now recognized as an important contributor to the development of atherosclerosis and cardiovascular disease. As defined, a patient with the metabolic syndrome has increased fasting glucose levels, increased blood pressure, lipid abnormalities, and obesity. Evidence of proinflammatory and oxidative stress also exists in these patients. Growing evidence suggests that OSA may contribute to the metabolic derangements that characterize the metabolic syndrome (see the image below).



View Image

Potential relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and the metabolic syndrome. OSAHS has been associated with 3 of the 5....

Multiple studies have shown that patients with OSA have increased glucose levels and increased insulin resistance.[107, 108, 109]

The most recent study, from 2004, was from the Sleep Heart Health Study.[109] In this study of 2000 research subjects, the prevalence of diabetic 2-hour glucose tolerance values rose from 9.3% in the group with an AHI less than 5-15% in the group with an AHI greater than 15. The odds ratio for having an abnormal glucose tolerance test result was 1.44 for the group with an AHI greater than 15; insulin resistance was also highest in this group.

Correlations were also noted for the degree of oxygen desaturation at night, indicating that the OSAHS may contribute to insulin resistance as a result of the hypoxemia that occurs with the syndrome. However, in the Wisconsin Cohort Study, subjects with OSAHS were no more likely to develop diabetes mellitus than subjects without OSAHS.[110]

OSA has been associated with increased production of reactive oxygen species[111] and other oxidative stress biomarkers.[112] It has also been associated with increased levels of several proinflammatory cytokines and markers associated with atherosclerosis. These include C-reactive protein (CRP) in both adults and adolescents,[113, 114] interleukin 6,[113] interleukin 18,[115] and matrix metalloproteinase 9.[116] However, at least one large epidemiologic study found no relationship between the severity of OSAHS and CRP levels.[117]

Oxidant-related microcirculatory endothelial dysfunction, in a group of patients who had no known vascular disease, improved when CPAP effectively treated the patient’s OSA, compared with no improvement in the control group.[118]

OSA has been associated with decreased production of nitric oxide.[119] Several studies have shown impaired vasodilator responses, as measured by either flow-mediated dilatation[120] or reactive hyperemic blood flow[121] techniques. Impaired flow-mediated dilatation was found to best correlate with the degree of oxygen desaturation in an epidemiologic cohort study.[122] Recent studies also indicate that cerebrovascular responses are impaired in patients with OSA.

Note that for most of these abnormalities associated with the metabolic syndrome, evidence from studies with a small number of subjects suggests that CPAP partially reverses the metabolic abnormality that is the focus of the study. That is, CPAP decreased insulin resistance, decreased lipid peroxidation, and increased vasodilator responses.

Diabetes in Obstructive Sleep Apnea

OSA is associated with an increased risk of type 2 diabetes. Whether OSA causes type 2 diabetes or whether it is associated with insulin resistance and diabetes is unclear. Use of CPAP can reverse insulin resistance. Sleep fragmentation, sleep deprivation, and hypoxemia (which all occur in OSA) are thought to play independent roles in glucose intolerance. Conflicting results show that reversal of glucose intolerance may occur when OSA is treated.

A 2009 study increases support for the role of OSA in exacerbating insulin control in patients with type 2 diabetes. This was found as an effect, independent of adiposity and other confounders.[123]

Obstructive Sleep Apnea in Special Populations

Elderly persons

The prevalence of OSA increases with age.[36] However, the clinical significance of OSA in healthy, community-dwelling people has been questioned because these people do not show significant sequelae (eg, sleepiness).

Elderly patients presenting to sleep centers for evaluation have similar symptomatology (including EDS) and PSG results compared with patients who are not elderly, except that elderly patients underreport snoring as a chief complaint, they tend to be less obese, and they are less objectively sleepy based on MSLT results. Thus, all elderly people, particularly if overweight, should be questioned about snoring, witnessed apneas, and daytime sleepiness and should be referred for evaluation if necessary.

Age does not appear influence compliance with CPAP therapy.[124, 125] Thus, all elderly patients with significant and symptomatic OSAHS should be offered therapy.

Children

OSA has an estimated prevalence of 2% in children, affecting boys and girls in equal numbers. Children most often present with loud snoring and symptoms and signs of adenotonsillar hypertrophy. Adenotonsillar hypertrophy is the predisposing factor in the majority of cases, although obesity is becoming a more common factor as the prevalence of obesity in children increases. Craniofacial syndromes (eg, Pierre Robin syndrome) and trisomy 21 are also predisposing factors in children.

EDS is not a common symptom in children with OSA. Instead, school-aged children often report problems with schoolwork. Studies have shown improvement in cognitive function and/or grades after adenotonsillectomy in children with OSA.[126, 127, 128, 129] Evidence suggests an association between attention-deficit/hyperactivity disorder and OSA in children.[130, 131]

Also, study findings presented at the 2013 annual meeting of the American Thoracic Society suggest that childhood-onset asthma may raise the risk of subsequently developing OSA.[132] Asthma was an independent risk factor for incident OSA at 8 years. After sex, age, body mass index, nasal congestion or stuffiness, smoking status, and number of alcoholic drinks per week were controlled for, childhood-onset asthma was associated with a greater than 2-fold risk of developing OSA (odds ratio [OR], 2.16; P< .05), whereas adult-onset asthma increased the risk by more than half (OR, 1.57; P< .05).

Resection of the enlarged tonsils is the standard therapy for the majority of children presenting with OSA; CPAP use is becoming more common as more children with obesity and craniofacial syndromes are recognized to have OSA.

Pregnant women

Several case reports associate intrauterine growth restriction (also termed intrauterine growth retardation) in pregnant women with concomitant untreated OSA. A study from Sweden found that hypertension, preeclampsia, low Apgar scores, and intrauterine growth restriction were more common in habitually snoring pregnant women than in nonsnoring pregnant women.[133] Habitual snoring was independently predictive of hypertension and growth restriction after correcting for other factors (eg, weight, age, smoking status).

These data suggest a link between SDB (indicated by the snoring) and pregnancy complications. Therefore, evaluation of all pregnant women with signs and symptoms of OSA is recommended, and they should be started on CPAP to prevent complications.

One study, however, found that whereas self-reported snoring increased in pregnant women (23% of women by the last week of pregnancy in the Swedish study), the prevalence of OSA was not higher. This suggests that pregnant women should be referred for evaluation only if the snoring is loud, habitual, and associated with other symptoms of OSA.

Long-distance truck drivers

Older data indicated that commercial truck drivers have an increased prevalence of OSA. However, more recent data indicate that the prevalence is no different from the general population. Risk factors are similar to the general population but also include short sleep durations.

Evidence from both the United States and Australia found no relationship between OSA severity and crash rate in commercial drivers, except possibly for a relationship between severe OSA and severe crashes (those that involve multiple injuries or motor vehicle towed from the scene). However, because of the potential for risk, a review and guidelines have been published to guide the physician.[134, 135, 136]

Other Associated Risks

Additional risk factors for developing obstructive sleep apnea (OSA) include the following:

Patients with OSA are also at risk for the following:

Approach Considerations

Guidelines developed in 2014 by the American College of Physicians include a recommendation that patients with daytime sleepiness should undergo a sleep study, preferably polysomnography (PSG, see the image below). According to the recommendations, physician assessment should include evaluation of risk factors and common presenting symptoms for obstructive sleep apnea (OSA). The best-documented risk factor is obesity.[138, 139]



View Image

MRI rendering of a patient without obstructive sleep apnea (OSA) (left panel) and a patient with OSA (right panel).

Sleep specialists differ in their acceptance of home sleep testing and how it should be used. The American Academy of Sleep Medicine (AASM) has guidelines on its use. Over time, portable sleep testing will evolve into a niche of diagnostic testing that will meet a community standard of sleep medical care.

Modalities available for identifying the site of obstruction include lateral cephalometry, endoscopy, fluoroscopy, computed tomography (CT) scanning, magnetic resonance imaging (MRI), and radiography. The accuracy of these methods for identifying the sites of obstruction is not clear. At present, upper airway (UA) imaging is used primarily as a research tool. Routine radiographic imaging of the UA is not performed.

Go to Upper Airway Evaluation in Snoring and Obstructive Sleep Apnea for complete information on this topic.

Pulmonary function tests (PFTs) are not indicated to make a diagnosis of or treatment plan for OSA alone. The PFT standard indications apply to OSA patients as with any other patient. Comorbid conditions with OSA that may require PFTs are listed in the text.

Lab Studies

Routine laboratory tests usually are not helpful in OSA in the absence of a specific indication. A thyrotropin test should be performed on any patient with possible OSA who has other signs or symptoms of hypothyroidism, particularly in elderly individuals.

A study by Cintra et al studied 150 subjects (75 patients and 75 control subjects, matched for age and sex). They determined that cysteine levels were higher in patients with OSA compared with control subjects, and levels were reduced after effective OSA treatment.[140] Thus, cysteine may be a potential biomarker of OSA.

Polysomnography

A PSG is necessary to accurately diagnose OSA and to assess treatment benefit. Data are collected in the laboratory in the presence of a qualified technician (ie, full PSG with attended monitoring). This protocol provides the opportunity to directly observe a variety of sleep-associated disturbances (eg, apneas, periodic leg movements, seizures, rapid eye movement [REM] behavior disorder). Patients who regularly work night shifts should undergo PSG during the day to match their normal sleep-wake cycle.

AASM standards and guidelines for diagnostic PSG

The AASM has published standards and guidelines for performing PSG (see American Academy of Sleep Medicine).[2] Having a patient studied at an AASM-accredited sleep disorders center is important because such centers adhere to standards that have been established by the AASM. This includes the criterion standard test for sleep disorders: the sleep disorders center PSG.

AASM guidelines for the indications and performance of PSG include the following:

Obstructive apnea is the cessation of airflow for at least 10 seconds with persistent respiratory effort (see the image below).



View Image

Obstructive sleep apnea. Note the absence of flow (red arrow) despite paradoxical respiratory effort (green arrow).

Central apnea is the cessation of airflow for at least 10 seconds with no respiratory effort (see the images below).



View Image

Central sleep apnea (thick areas). Note the absence of both flow and respiratory effort (green double arrows).



View Image

Comparison of a central apnea (box) and obstructive apnea (circle).

Mixed apnea is an apnea that begins as a central apnea and ends as an obstructive apnea (see the image below).



View Image

Mixed sleep apnea. Note that the apnea (orange arrow) begins as a central apnea (effort absent; red double arrow) and ends as an obstructive apnea (ef....

Hypopnea is a 30% or greater decrease in flow lasting at least 10 seconds and associated with a 4% or greater oxyhemoglobin desaturation. An alternative definition is a 50% or greater reduction in flow lasting at least 10 seconds and associated with either a 3% or greater oxyhemoglobin desaturation or an arousal (see the image below).



View Image

A 2-minute recording of sleep showing 4 hypopneas (thick arrows) and associated oxygen desaturations (red arrows). This recording illustrates the recu....

Respiratory event–related arousal (RERA) is an event in which patients have a series of breaths with increasing respiratory effort or flattening of the nasal pressure waveform leading to an arousal from sleep that does not otherwise meet the criteria for an apnea or hypopnea.

Arousals detected on PSG are important for the evaluation of the degree of sleep fragmentation. They may be the only clue to UA resistance syndrome (UARS) in a patient with daytime hypersomnolence if esophageal pressure is not monitored. Monitoring of esophageal pressure is not routinely performed in most laboratories because of the invasive nature of the procedure.

PSG findings characteristic of OSA

The following PSG findings are characteristic of OSA:

The apnea-hypopnea index (AHI) is derived from the total number of apneas and hypopneas divided by the total sleep time. A normal cutoff for AHI has never been defined in an epidemiological study of healthy people. Most sleep centers use a cutoff of 5-10 episodes per hour. The severity of OSA is arbitrarily defined and differs widely between centers. Recommendations for cutoff levels on AHI include 5-15 episodes per hour for mild, 15-30 episodes per hour for moderate, and more than 30 episodes per hour for severe.

Split-night PSG

Patients with a respiratory disturbance index (RDI) higher than 40 during the first 2 hours of diagnostic PSG should undergo a split-night PSG study. The final portion of the study is used for titrating the continuous positive airway pressure (CPAP) device. Split-night studies may be considered for patients with an RDI of 20-40, as based on clinical observations (eg, prolonged obstructive events, marked oxygen desaturation). A minimum of 3 hours of sleep is preferred to adequately titrate the CPAP device after this treatment is started.

Split-night studies require recording and analysis of the same parameters as those evaluated in standard diagnostic PSG. A single split-night study may not permit adequate titration of CPAP therapy. If treatment does not control symptoms, additional full-night CPAP titration may be required.

Repeat PSG

If symptoms persist despite adequate adherence to prescribed CPAP treatment (see Treatment and Management), PSG should be repeated. PSG can be used to assess response to UA surgical procedures and to assess response to oral appliance (OA) therapy. If sustained weight change of greater than 15% occurs, PSG should be repeated. If results of the first PSG are of poor quality, a repeat study is indicated.

Patients who stop REM sleep–suppressant medications should be restudied, if symptomatic on treatment, because OSA is most prevalent in REM sleep. The OSA that occurs during REM sleep should be examined whenever possible to avoid undertreatment of the OSA or a false-negative diagnosis on a diagnostic study.

Home testing

Considerable debate exists about the validity of portable testing for the diagnosis of OSA compared with a sleep disorders center PSG. The increasingly common use of home testing, especially since the Centers for Medicare and Medicaid Services (CMS) published guidelines for practitioners to receive payment for conducting them. An important part of the guidelines requires that portable testing can only be performed in conjunction with accredited sleep disorders centers. Studies have not proven that portable testing is superior to PSG testing. Cost analysis studies comparing no testing versus in-sleep-center PSG testing showed that in-sleep-center PSG was cost effective. Portable testing was not included in that analysis; however, it stands to reason that if PSG was cost effective compared with no testing, PSG would be cost effective compared with portable testing.

The 3 levels of portable monitors are (1) level 2, a portable monitor with the same parameters as a full attended PSG (includes EEG); (2) level 3, with at least 4 channels, including flow, effort, oximetry and heart rate; and (3) level 4, with fewer than 4 channels, often oximetry with flow or oximetry alone.

Level 3 portable monitors have the largest body of supportive evidence for use in diagnosing OSA. In general, level 3 monitors are best used to confirm the diagnosis of OSA rather than to rule it out. In addition, most of the studies using portable monitoring have validated the equipment in the laboratory, not in the home, and have done so in patients with high probability of disease and without significant comorbidities (particularly heart and lung disease).[141, 142]

At least 2 studies have compared an at-home approach to diagnosis and treatment of OSA (home portable monitoring followed by autotitrating CPAP [see below]) to a conventional in-laboratory sleep study. Both studies showed that in carefully selected patients (generally those with a high pretest probability of disease and without comorbidities), patients with a home-based approach had similar clinical outcomes to those patients studied in the laboratory.[143, 144] A study by Kuna et al also reported that functional outcome and treatment adherence in patients evaluated using a home-testing algorithm was not clinically inferior to standard in-laboratory polysomnography.[145]

Chai-Coetzer et al developed a simplified, two-stage model for identifying OSA in primary care. The model used a screening questionnaire followed by home sleep monitoring.[146] The two-stage model was found to be accurate in identifying OSA in primary care and may allow expedited care for patients.

Published in 2017, the results of a multicenter, randomized, noninferiority study (n=406) conducted by Chai-Coetzer et al support manually scored level 3 home testing in routine practice.[147] Poorer outcomes were seen with level 4 testing, perhaps attributable to physician confidence.  Further details can be found in the article Home Sleep Testing as Good as Laboratory Testing for Apnea.[148]  

In patients with a high probability of obstructive sleep apnea, home sleep apnea testing is not inferior to in-laboratory PSG. It is important to keep in mind that home sleep tests do not measure sleep and may underestimate the degree of sleep apnea, which may lead to false-negative findings in some patients, particularly for those who have insomnia, other coexisting sleep disorders, or other medical conditions that are contraindicated for home sleep apnea testing.

The AASM’s published guidelines on the use of portable monitors recommend that they be used only in patients with a high probability of disease and those without comorbidities (particularly congestive heart failure) and that negative studies be followed by a full, attended study.[149]

It is generally expected that more sleep centers will be adopting home portable monitoring for patients in the future. In theory, a home-based approach to testing will lead to faster diagnosis and treatment for a subset of patients with high probability of disease.

A novel disposable skin patch has been developed that may detect sleep apnea with accuracy comparable to traditional PSG.[150, 151] In a study of 179 subjects, dual overnight recordings were included from 174 patients; clinical agreement rates between the patch and PSG were 87.4% (95% confidence interval, 81.4-91.9%). The results from the study will be the basis for an application for approval from the US Food and Drug Administration (FDA).

See Obstructive Sleep Apnea and Home Sleep Monitoring for more information.

Multiple Sleep Latency and Maintenance of Wakefulness Tests

The measurement of sleepiness and alertness remains controversial (ie, the multiple sleep latency test [MSLT] for objectively measuring sleepiness and the maintenance of wakefulness test [MWT] for measuring alertness).[152]

The MSLT may follow PSG. It is considered an objective measurement of excessive daytime sleepiness (EDS). The MSLT consists of 4-5 naps of 20-minute duration every 2 hours during the day. The latency to sleep onset for each nap is averaged to determine the daytime sleep latency. Normal daytime sleep latency is greater than 10-15 minutes. OSAHS is generally associated with latencies of less than 10 minutes. It is not uncommon for the MSLT to demonstrate profound daytime sleepiness in OSA patients; mean sleep latency cannot discriminate between patients with OSA and patients with narcolepsy.

Routine use of the MSLT in the evaluation of OSA has significantly decreased because sleep physicians generally treat OSA on basis of the subjective symptoms reported by the patient. The MSLT is generally used to confirm the diagnosis of narcolepsy in patients in whom narcolepsy is a consideration. As opposed to people without narcolepsy, narcoleptic patients have rapid eye movement sleep on at least 2 of the 4-5 naps during the day.

Whether the MWT is a good enough test to measure treatment efficacy is debated. The low correlation between self-reported sleepiness, as typically measured by the Epworth Sleepiness Score (ESS), and objective measures of sleepiness, as measured by the MSLT, continues to present a problem to clinicians and researchers in the determination of how to use these disparate measures in clinical practice and in research.

Approach Considerations

Obstructive sleep apnea (OSA) should be diagnosed and treated promptly. Board-certified sleep specialists evaluate polysomnography (PSG) results and make treatment recommendations for OSA patients. Treatment depends in part on the severity of the sleep-disordered breathing (SDB). People with mild apnea have a wider variety of options, while people with moderate-to-severe apnea should be treated with nasal continuous positive airway pressure (CPAP).

General and behavioral measures, such as weight loss, avoidance of alcohol for 4-6 hours prior to bedtime, and sleeping on one’s side rather than on the stomach or back, are elements of conservative nonsurgical treatment. In a 2006 practice parameter, both weight loss and positional therapy were rated as “guidelines,” indicating a patient care strategy with a moderate degree of evidence.[153, 154]

Because obesity is a major predictive factor for OSA, weight reduction reduces the risk of OSA. The best data suggest that a 10% reduction in weight leads to a 26% reduction in the respiratory disturbance index (RDI). Benefits of weight reduction in patients with SDB include the following:

Weight gain is one of the most important determinants of relapse of OSA after surgical treatment. Although accomplishing and maintaining weight reduction are difficult, the results are extremely beneficial when patients can do so. The treatment approach to SDB is not complete if weight reduction is not addressed in patients who are obese.

Mechanical measures include positive airway pressure with a CPAP or bilevel positive airway pressure (BiPAP) device and oral appliance (OA) therapy. CPAP is the standard treatment option for OSA and generally can reverse this condition quickly with the appropriate titration of devices.

OAs are indicated for (1) patients with mild-to-moderate OSA who prefer oral appliances to CPAP devices, (2) patients with mild-to-moderate OSA who do not respond to CPAP therapy, and (3) patients with mild-to-moderate OSA in whom treatment attempts with CPAP devices fail. They should not be considered effective therapy for patients with severe OSA.

Pharmacologic therapy is not part of primary treatment. No clinically useful drug therapy is currently available, except in certain cases of excessive sleepiness remaining after apparently successful treatment.

From least invasive and effective to most invasive and effective, treatments can be summarized as follows:

Improving treatment adherence is important to the care of OSA patients. Whereas adherence in OSA patients is comparable to that in patients taking medications, such as statins, a body of research on adherence seems to have been largely ignored and needs to be integrated into sleep medicine clinical practice.

Studies showing how to improve CPAP adherence exist as well and should be integrated into a standard CPAP follow-up program to improve adherence; the same could be said for OA therapy to the degree that some of the methods and assessment are common to both treatments.

Unlike CPAP/BiPAP treatment adherence, OA treatment adherence is not objectively measured. Therefore, studies comparing adherence between OA and CPAP/BiPAP therapy cannot be considered with confidence in the outcome. As when CPAP/BiPAP did not have objective adherence data, OA treatment adherence is probably lower than published values that have relied on patient or practitioner self-report.

Sleep-related breathing disorder continuum

The concept of the sleep-related breathing disorder (SRBD) continuum (see Pathophysiology) suggests that optimal OSA treatment must correct OSA, upper airway resistance syndrome (UARS), and snoring. If it does not eliminate all 3 problems, the symptoms and the pathophysiological process that was evident at the start of disease recur. Therefore, in the treatment of SRBD, CPAP corrects OSA first, UARS next, and snoring last.

An unlikely occurrence is snoring being corrected before OSA and/or UARS; if this is thought to have occurred, then consideration should be given to the integrity of the snoring microphone.

Consider whether snoring has been correctly interpreted on PSG during a CPAP titration. When a mask leak occurs, the noise may be transferred by the microphone to the PSG snore channel and may sound like snoring. One can determine the difference between snoring and a CPAP mask leak because snoring occurs at the point of peak inspiration and the beginning of expiration; mask leak occurs during expiration.

Consider whether the patient has had upper airway (UA) corrective surgery. If pharyngeal tissue has been eliminated, snoring may not occur, but OSA can develop (so-called silent apnea).

Nasal CPAP Therapy

Initially described in 1981, nasal CPAP therapy is the most effective treatment for OSA, and it has become the standard of care for this condition. (It is also effective for treating mixed apneas and some central apneas.)

The CPAP device consists of a blower unit that produces continuous positive-pressure airflow. This airflow is usually applied at the nose and is then directed through the UA. CPAP increases the caliber of the airway in the retropalatal and retroglossal regions (see the image below). It increases the lateral dimensions of the UA and thins the lateral pharyngeal walls, which are thicker in patients with obstructive sleep apnea than in people without obstructive sleep apnea.



View Image

Top image is 3-dimensional surface renderings of the upper airway demonstrating the effect of progressive increases in continuous positive airway pres....

Effectively, CPAP acts as a pneumatic splint to maintain UA patency during sleep, preventing the soft tissues from collapsing. By this mechanism, it effectively eliminates the apneas and/or hypopneas, decreases the arousals, and normalizes the oxygen saturation (see the image below).



View Image

Effect of nasal continuous positive airway pressure (CPAP) on oxygen saturation in sleep apnea. The upper portion of this figure shows the raw oxygen ....

Guidelines for use

Patients with severe SDB (respiratory disturbance index [RDI] >20-30) should be treated irrespective of their symptoms because of the increased risk of cardiovascular morbidity. Patients with an RDI of 5-20 should be treated if they have symptoms or coexistent cardiovascular disease. Patients with UARS may need CPAP therapy.

Medicare guidelines specify criteria for ordering CPAP for patients with OSA. All patients with an apnea-hypopnea index (AHI) greater than 15 are considered eligible for CPAP, regardless of symptomatology. For patients with an AHI of 5-14.9, CPAP is indicated only if the patient has one of the following: excessive daytime sleepiness (EDS), hypertension, or cardiovascular disease.

Most sleep center physicians still titrate CPAP during a sleep study, either as a second night of study or during the second half of a diagnostic study (ie, split-night PSG [see Workup]). Proper titration includes identifying the minimum CPAP level that abolishes obstructive apneas and/or hypopneas, oxyhemoglobin desaturation, respiratory effort–related arousals (RERAs), and snoring in all sleep stages and all sleep positions. The pressure needed is typically 5-20 cm H2 O. Guidelines for positive-pressure titration have been published.[155, 156, 157]

Currently, CPAP devices are available that automatically change pressures based on the presence and/or absence of OSA (auto–positive airway pressure, or auto-PAP). The rationale for auto-titrating devices is that the pressure required to treat OSA may vary over the course of the night and between different nights, sleep stages, and body positions, with the variations not captured by a one-night titration study.

In theory, the mean pressure delivered by auto-PAP devices is lower than that delivered with fixed CPAP; however, no studies have shown increased patient compliance with auto-PAP devices.[158] In fact, a randomized crossover study comparing fixed and variable pressure CPAP, the largest to date (N = 200), found a marginal increase in hours used per night (0.2 h) but no difference in patient preference, which actually showed an order effect (patients preferred the type of device first used in the study).[159]

Guidelines from 2008 indicate that auto-PAP devices may be used during an attended sleep study to determine a single pressure for use at home (guideline recommendation). In addition, some evidence supports use in the unattended setting to determine a single pressure for home use (option recommendation).[160]

Effectiveness

Application of adequate levels of nasal CPAP during sleep almost always resolves obstructive apnea and/or hypopnea, oxyhemoglobin desaturation, RERAs, and snoring from sleep. It also results in adequate sleep continuity.

CPAP has been shown to improve daytime sleepiness, mood, and cognitive function in people with both mild and moderate apnea.[161, 162]

CPAP has also been shown to decrease blood pressure, primarily in patients with severe OSA.[92, 93, 91] Evidence also indicates that it may improve the left ventricular ejection fraction in patients with congestive heart failure and OSA.[99] CPAP plus an antihypertensive medication may synergistically improve systemic hypertension.[95] In addition, it improves right-side heart function and pulmonary hypertension.

A study of 86 patients with sleep apnea, including 75 who had metabolic syndrome, suggests that CPAP is associated with a lower risk for heart disease, stroke, and diabetes. Study participants were treated for 3 months with either CPAP or sham CPAP, followed by a month of no treatment and 3 additional months of the opposite treatment. Of patients treated with CPAP, 13% no longer met diagnostic criteria for metabolic syndrome, compared with 1% of patients in the sham-CPAP control group. CPAP use was also associated with significant weight loss.[163]

CPAP has also been shown to increase quality of life[164] and decrease health care costs.[165] Prospective cohort studies suggest that CPAP reduces mortality in OSA.[46, 54] The benefits parallel those observed after tracheostomy.

Although many OSA patients note an immediate improvement in alertness, concentration, and memory, achieving maximum improvement in neurocognitive symptoms may take as long as 2 months. Follow-up visits should be scheduled at least once after CPAP treatment is first started and at least yearly thereafter. Follow-up evaluation is required to ensure symptomatic improvement, CPAP adherence, and equipment maintenance.

In an attempt to determine to what extent CPAP benefits its users, the authors of a randomized controlled trial evaluated the effects of stoppping CPAP treatment. Results show a rapid recurrence of OSA and sleepiness within a few days of CPAP withdrawal. Also, study participants experienced deteriorated endothelial function and a marked increase in heart rate after 2 weeks.[166]

In one meta-analysis of three randomized placebo-controlled trials, nearly 30% of the treatment benefit among high users of CPAP was due to patients’ expected benefit of treatment due to their knowledge of hours of device use.[167]

Adherence

CPAP adherence is key to patients obtaining benefits from its use. Unfortunately, adherence may be poor. Evidence indicates that many patients do not accept (or even initiate) CPAP therapy and that up to 25% do not regularly follow up with a sleep physician,[168] with most of these patients being nonadherent to therapy.

Compliance with CPAP therapy can be objectively measured.[46] Most modern CPAP devices measure both "machine-on" and "mask-on" times, with the mask-on time used to measure compliance. Compliance data are downloaded onto electronic chips from which compliance reports can be downloaded during follow-up appointments. These reports allow the physician to have real-time data on compliance, allowing him or her to immediately address problems. Examples of a compliance report are shown in the image below.



View Image

Examples of good (upper panel) and poor (lower panel) compliance. In the upper panel, the patient is using continuous positive airway pressure (CPAP) ....

Many studies have examined how many nightly hours use is necessary for CPAP to render salutary effects. A study published in 2009 demonstrated that persons who wore their CPAP device for 5.6 hours per night experienced a slight decrease in blood pressure.[94] CPAP adherence was related to the AHI and decreased scores on the Epworth Sleepiness Scale (ESS); this effect was robust because patients with abnormal ESS scores were excluded from the study

Generally, patients have been considered compliant if they use their CPAP device more than 4 hours per night, 5-7 nights per week. However, a 2007 study questioned what is optimal CPAP usage.[169] In this study, nightly duration of use required to normalize daytime functioning was examined for 3 common functional measures. The thresholds above which further improvements were less likely were 4 hours for the ESS score, 6 hours for the multiple sleep latency test (MSLT), and 7.5 hours for the Functional Outcomes of Sleep Questionnaire.

This study illustrates that patients who are considered to have good compliance by accepted definitions may, in fact, be undertreated and that patients should be encouraged to use positive airway pressure for at least 7 hours per night.

Evidence now indicates that CPAP compliance may be determined as early as 2 weeks after CPAP is initiated.[170, 171, 172] Patients who consistently use their positive airway pressure device at 6 months were, on average, using the device for more than 2 hours more per night during the first 2 weeks and were more ready and confident to continue use. On the other hand, intermittent users were more likely to report adverse effects from the device, general discomfort, and that the device was too inconvenient.

In a study of long-term compliance, 68% of patients were using a CPAP machine at 5 years. Predictors of long-term compliance were baseline AHI and degree of sleepiness. However, the best predictor of compliance was regular use at 3 months of therapy, indicating that physicians must work to increase patient compliance early in the treatment period.[173]

CPAP adherence has often been assessed outside the context of adherence in other areas of medicine. In that context, CPAP adherence rates appear dismal.

However, in a prospective study of severe OSA patients investigating whether adherence or nonadherence to CPAP treatment predicted adherence to 3 well-known protective cardiovascular medications, CPAP adherence did not predict adherence with these medications.[123] The adherence with the medications was not surprisingly low, given what is known about adherence (81-95% adherence to the medication). Again, with severe OSA (AHI > 30) and comorbid heart disease, medication adherence was low, despite CPAP adherence.

In another study, patients who consistently refilled lipid-lowering medications were more adherent to CPAP.[174] However, being married was the most powerful predictor of adherence. Once marital status entered the regression model, CPAP adherence and medication adherence were not significant predictors of adherence. This study demonstrates the complexity of the assessment of adherence.

A systemic review and meta-analysis by Bakker and Marshall examined the use of flexible pressure delivery of PAP.[175] Although flexible pressure delivery intends to improve comfort and compliance through reduction of pressure during early exhalation, the study found that this flexible pressure modification does not significantly improve compliance with CPAP in patients with OSA.

Split-night PSG does not adversely affect short-term CPAP adherence in patients with OSA.[176] Additionally, full-night PSG performed so patients can have a full night in the sleep disorders center to adapt to CPAP has not been shown to improve adherence.[176]

An individualized approach in which reasons for poor compliance are systematically investigated is essential to improving compliance. Poorly adherent patients should be asked about mask fit, mask leak, sinus/nasal congestion, mouth breathing, and general sleep habits to determine reasons for nonadherence.

Interventions to improve compliance include (1) attendance in a group clinic with education provided, (2) group cognitive behavioral therapy provided as two 1-hour sessions that include an educational talk and video of real CPAP users, (3) written literature and weekly phone calls during the first month of use, (4) use of nasal humidification, (5) alternative mask interfaces, and (6) prompt attention to adverse effects and nasal/sinus congestion (see Complications and adverse effects).[177, 178, 179, 180, 181, 182]

Patient education with sleep specialists has been shown to improve adherence. Patients who attended the authors’ short information program showed higher daily usage and lower subjective daytime sleepiness. These results suggest that patients on CPAP therapy may benefit from education, even after a longer treatment period.[183]

Pressure-relief CPAP, a system that lowers the pressure at the onset of expiration, is hypothesized to improve adherence by reducing the uncomfortable sensation of breathing against high pressure while maintaining a patent upper airway. However, a review of the literature has not found that adherence to therapy is greater in patients using pressure-relief CPAP.[158] Despite this, the author’s center frequently prescribes pressure-relief CPAP for all patients who require a setting of greater than 10 cm water.

Although an average of 20-40% of patients do not use the prescribed therapy, some sleep disorder centers have achieved greater than 90-95% adherence rates with CPAP therapy. In the authors’ experience, regular, close, and personalized follow-up greatly enhances adherence.

Complications and adverse effects

Pressure- and airflow-related complications include a sensation of suffocation or claustrophobia, difficulty exhaling, inability to sleep, musculoskeletal chest discomfort, aerophagia, and sinus discomfort. Pneumothorax and/or pneumomediastinum (extremely rare), pneumoencephalos (isolated case report), and tympanic membrane rupture (rare) also can occur.

Patients with claustrophobia may try using nasal pillows or behavioral management. If patients feel a sensation of increased resistance to expiration, use of a CPAP unit with a ramp feature is indicated. This unit permits the patient to fall asleep with little or no pressure applied, and the pressure gradually increases to the set optimal level over a predetermined interval (usually 15-30 min). BiPAP may be used as an alternative.

Mask-related problems include skin abrasions, rash, and conjunctivitis (due to air leaks). If excessive air leaks through the mouth, patients should use a chin strap to keep their mouths closed or they should try an oronasal mask. Consider consultation with an otolaryngologist to rule out sinus dysfunction. If a poorly fitting mask causes skin breakdown and/or air leaks, patients should try masks of different sizes and/or models; a variety of interfaces are now available.

Nasal problems can include rhinorrhea, nasal congestion, epistaxis, and nasal and/or oral dryness. Nasal congestion can be treated with antihistamines and/or topical corticosteroids. Nasal dryness can be treated with topical saline sprays or humidification. If the air generated by the unit is too cold, the patient should use a heated humidifier.

Other problems include noise and spousal intolerance.

Medicare and Medicaid coverage

For Medicare and Medicaid patients, regulations state that the coverage of CPAP is initially limited to a 12-week period for beneficiaries diagnosed with OSA as determined Centers for Medicare and Medicaid Services (CMS) criteria. CPAP is subsequently covered for those beneficiaries diagnosed with OSA whose OSA improved as a result of CPAP treatment during this 12-week period.

CPAP for adults is covered by Medicare and Medicaid when OSA is diagnosed using a clinical evaluation and findings from one of the following assessments are positive:

For more information, see Decision Memo for Continuous Positive Airway Pressure (CPAP) Therapy for Obstructive Sleep Apnea (OSA) (CAG-00093R2).

Go to Obstructive Sleep Apnea, Home Sleep Monitoring for complete information on this topic.

BiPAP Therapy

Some patients require the use of BiPAP. In contrast to CPAP, which delivers a constant pressure during both inspiration and expiration, BiPAP permits independent adjustment of the pressures delivered during inspiration and expiration. The levels are set so that the expiratory positive airway pressure eliminates apneas and the inspiratory positive airway pressure eliminates hypopneas.

The ability to adjust inspiratory and expiratory pressures independently results in lower mean airway pressures compared with those of CPAP. In a given patient, the expiratory positive airway pressure level that must be applied is lower than the corresponding CPAP level required to maintain airway patency.

BiPAP is generally used in patients who cannot tolerate high CPAP pressures (ie, patients who experience difficult exhalations) or who have barotrauma complications (eg, ear infections, bloating). Many laboratories automatically place a patient on BPAP if the CPAP level needs to be increased above 15 cm water. However, BiPAP is too expensive to be used as first-line therapy, and it has no distinct advantages over CPAP therapy.

Compliance with BPAP has not been demonstrated to be better than compliance with CPAP.[184, 185]

Oral Appliance Therapy

OAs act by moving (pulling) the tongue forward or by moving the mandible and soft palate anteriorly, enlarging the posterior airspace. They open or dilate the airway.

Newer designs have separate upper and lower parts that are attached to each other and that allow for adjustability and jaw mobility. A minimum percentage of protrusion to effectively treat OSA is 6-10 mm or up to 75% of the maximum protrusion the patient is capable of performing upon request at the initial examination. This protrusion advance distance is necessary for the OA to be effective. The more protrusion gained, the lower the AHI at the treatment assessment time point.

Multiple different devices are available on the market. At present, the 3 basic designs of OAs used to treat sleep-related breathing disorders (SRBDs) are mandibular repositioners, tongue-retaining devices (TRDs), and palatal-lifting devices. More than 40 OAs are available to manage SRBD and obstructive sleep apnea.

Go to Oral Appliances in Snoring and Obstructive Sleep Apnea for complete information on this topic.

Guidelines for use

The American Academy of Sleep Medicine (AASM) has published practice parameters and a review of the use of OAs in persons with OSA.[186, 187] These parameters include the following recommendations:

According to the standards and guidelines listed above, the major role for OA therapy appears to be the treatment of patients with mild-to-moderate OSA who cannot tolerate CPAP (and BiPAP) therapy. These devices are relatively unlikely to benefit patients with severe OSA. Clinicians and patients prefer a titratable device, such as a mandibular repositioner, because it can be adjusted to improve both effectiveness and comfort.

Patients should receive a complete evaluation by a sleep disorders specialist and a dental professional, both of whom should be experienced in OA therapy; their close collaboration is required. Follow-up PSG after final fitting helps confirm that OA therapy is treating OSA adequately; no other method is available for this purpose (the device should not be titrated during the course of an assessment study).[188] . OA devices may resolve snoring without adequately treating OSA.

Remember that the AHI may increase with OA treatment. A change in AHI may be due to weight change between the first study and the final OA titration, not always due to the OA appliance itself. Also recognize that the AHI may vary from night to night because of the degree of severity of the obstructive sleep apnea itself; persons with mild-to-moderate obstructive sleep apnea have higher AHI variability compared with those who have more severe obstructive sleep apnea, and OA therapy is not typically used in patients with more severe obstructive sleep apnea.

Night-to-night variability in supine sleep position also occurs, and supine is the position in which OA has been thought to render its greatest benefit, including rapid eye movement (REM) sleep percentage. REM sleep percentage can increase with adaptation to the testing procedure, and it can increase if a patient is taking a REM-suppressant medication that was discontinued (eg, selective serotonin reuptake inhibitors). All these factors, among others, can account for changes in the AHI.

Contraindications for OA treatment include the following:

Effectiveness

Multiple small cohort studies have shown that OAs effectively lower the AHI and improve overnight sleep architecture.

The biomechanical factors responsible for the effectiveness of OAs are not completely understood. Increased tone of UA musculature is thought to be the predominant influence on the caliber and volume of the airway. Key among these muscles is the genioglossus muscle. When the jaw is opened, the genioglossus (with other muscles in the pharyngeal airway) influences the airway to improve its caliber and stability.

OAs thin the lateral pharyngeal walls by exerting traction. According to imaging studies, the size of the lateral pharyngeal fat pads and the thickness of the lateral pharyngeal muscular walls are greater in patients with apnea than in healthy subjects. For OA therapy to be successful, the lateral dimension of the airway may be critical; however, data suggest that total airway space, measured as a 3-dimensional image using cone-beam computed tomography (CT) scanning, may be the most powerful predictor for OSA severity.

The ideal treatment goal for OA therapy, as with CPAP treatment, is an AHI of less than 5 and snoring resolution. The OA literature has generally regarded an AHI less than 10 as a treatment success. However, an AHI of greater than 5 is associated with adverse health consequences; therefore, an AHI of less than 5 without snoring should be the ideal treatment goal.

The 4 key variables that contribute to OA treatment efficacy are (1) mild-to-moderate OSA (AHI < 30), (2) mandibular repositioner protrusion distance greater than 70% of baseline, (3) higher supine AHI relative to lateral sleep position AHI, and (4) a lower body mass index (BMI).

Treatment success with mandibular repositioners (and with OAs in general) appears to be inversely related to the initial RDI. A growing body of evidence now suggests that the severity of OSA is predictive of the response to OAs.

Most studies that have examined the efficacy of OAs have used mandibular repositioners. However, a 2009 study investigated the effect of TRDs on OSA severity.[189] If ideal treatment is an AHI lower than 5 and no snoring, few patients met that goal. If ideal treatment is an AHI lower than 10, then 31% met that goal. Response variation was wide, with a standard deviation for AHI of 19.5. Two predictors of response were found using multiple regression: age and protrusion distance (mean protrusion, approximately 7±1.5 mm).

A review of the literature by the American Sleep Disorders Association (ASDA) indicated the following findings[188] :

Subsequent prospective controlled clinical trials to compare OA therapy with nasal CPAP therapy to treat OSA and snoring demonstrated the following results:

In general, comparative studies show that CPAP is more effective than oral appliances in lowering the AHI to less than 5-10 events per hour.[190] However, many other outcomes, such as sleepiness and cognitive functioning, are not different between the 2 devices. When asked which device the participant would use at home, the responses varied; in some studies, the participants favored CPAP and in others, they favored the oral appliance.

In a trial comparing health effects after 1 month each of CPAP and mandibular advancement device (MAD) therapy in 126 patients with moderate-to-severe OSA, the 2 treatments yielded comparable improvements in neurobehavioral outcomes and disease-specific quality-of-life outcomes; neither improved blood pressure. CPAP was more effective in reducing the apnea-hypopnea index, but the difference appeared to be offset by a higher treatment compliance in the MAD group. MAD was also more effective in improving 4 general quality-of-life domains.[191]

In one study, OAs were more effective than uvulopalatopharyngoplasty (UPPP) in the treatment of OSA. OAs may also be useful in managing OSAS if surgery fails.

The use of OAs in clinical practice is limited because of the difficulty in predicting the therapeutic response of individual patients. Tsai et al used a remote-controlled device to titrate OA treatment during a single-night sleep study to predict the therapeutic response.[192] In concept, this approach is similar to titrating nasal CPAP during a single-night sleep study.

Raphaelson et al[193] and Petelle et al[194] first demonstrated the titration of mandibular advancement during a sleep study. Petelle et al demonstrated that determining the optimum level of mandibular advancement required for an individual patient during a single-night study is possible. Of note, Tsai et al did not report the same.

Apart from raising the possibility of predicting therapeutic responses in individual patients, this titration approach potentially provides an opportunity to determine the optimum therapeutic dose of mandibular advancement required during a single-night sleep study.

Further work is required in this area because it could greatly affect the use of OAs in SRBDs. This research may yield the method required to identify patients who may respond to OAs and to determine the optimum level of advancement required for an individual patient.

Adherence

Adherence rates are not as well defined with OAs as they are with CPAP, because CPAP units have internal computerized recorders that capture data that can give feedback regarding hours of use each night. Most studies to date have used subjective measurement tools to determine OA adherence percentage. Unfortunately, this is a flawed approach, because self-report is unreliable; moreover, when adherence is compared with CPAP (when objective adherence has been measured), the outcome is meaningless.

Given that caveat, available evidence suggests that OA adherence is not high. Most studies have shown that fewer than 50% of patients use their appliance over time, and adherence is not universally defined. If self-report of use is inflated, as it typically is, actual adherence with OA therapy may be much lower.

In one study, only 52% of patients stated that they were using the TRD after 5 years. Of those, 79% wore the TRD more than 4 nights per week. Among nonusers, 47% went back to CPAP, 12% tried another type of OA and were satisfied, and 41% remained untreated.

This subanalysis of what patients who were noncompliant did is informative and instructive for other studies. First, it shows that CPAP may be preferred after another therapy has been tried over time, and, as mentioned, preference is not synonymous with adherence. Second, patients who do not adhere to one treatment do not automatically seek another treatment. Hence, the use of a TRD is not benign, because 41% of those who did not continue TRD treatment did not receive OSA treatment at all for 1-36 months.

This report by the authors was enlightening, because many studies do not go on to ask what alternatives were sought by the patient. Not seeking other treatment is a very important follow-up question to ask in nonresponders to any OSA treatment.

Adherence declines over time and is thought to be largely due to temporomandibular joint (TMJ) problems. Median adherence over the first year, for those who accepted OA treatment, has been shown to be 77%.

Each oral appliance device (>40 devices available) can have a unique adverse effect that leads to nonadherence. Given the literature, TMJ, occlusal changes, excessive salivation, and discomfort are likely to be chief among the reasons for nonadherence to effective OA treatment. As with all treatment, ineffectiveness is among the most prominent reasons patients do not adhere to treatment.

To assess the above mentioned concerns of OA treatment, OSA patients treated with an OA need to return to determine optimal fit and then at 6 months, 1 year, and annually thereafter. This standard is not different from good medical care for any sleep medical treatment (eg, prescription medicine, weight loss, CPAP, surgery).

Multiple PSG studies may be required to document a therapeutic response. Home studies seem indicated in these cases, with final verification using a full PSG in the sleep center.

Long-term follow up is very important in OA therapy. Insufficient data exist to determine if damage to teeth and joints occur in patients using OA therapy.

As noted, adherence data for OA treatment derive from subjective reports, whereas CPAP adherence can be monitored objectively. The development of objective measures of OA treatment would be of benefit in the future for patients and so that assessment of the adherence can be meaningfully compared between OA treatment, CPAP, treatment, and surgical correction over time.

Complications and adverse effects

Complications or adverse effects include excessive salivation, dental misalignment with bite change, and tooth movement. Additionally, OAs may aggravate or cause adverse occlusal changes (as early as 6 mo into treatment), TMJ disease, myofascial pain, tooth pain, gagging, gum irritation, salivation, TMJ sounds and morning-after occlusal changes, and/or tongue pain (most common with TRDs—from 67-68% of patients reported one or more of these adverse effects, and the adverse effects were noted to occur at any time during treatment).

Patients may also object to having an appliance in their mouth throughout the night.

Insurance coverage and cost

Cost may be a barrier to OA therapy. Although not all dental practitioners charge the same fee, common amounts range from $300 to more than $2,500.

The lack of long-term studies with OA therapy may limit the clinician from choosing it as an option. Unlike CPAP or surgery, OA therapy is often not covered by medical insurance plans. Check with individual insurance carriers to verify coverage.

The ASDA states, “Economic assessment, focusing on both short- and long-range costs (inclusive of needed follow-up and indirect costs of OA therapy) is needed so that OA therapy can be compared with alternate therapies through cost and effectiveness analyses. Research is needed to clarify design characteristics most beneficial in given patient groups, so that device selection is driven by data that are more precise.”[188]

Surgical Correction of the Upper Airway

Surgical correction of the upper airway (UA) is still performed but is not considered primary therapy for OSA. The theoretical advantage of surgery is that if the patient is cured, compliance with CPAP or OA therapy is no longer an issue. However, a primary reason why surgery has not become a standard therapy is the lack of any long-term outcome studies showing that surgical correction continues to be effective 5 or more years after it is performed.

Surgical care for OSA patients should not be seen as a "last ditch" effort in treatment of OSA patients. Surgery may be initial therapy for patients with mild OSA (RDI < 20, lowest oxyhemoglobin saturation >90%) if medical therapy is refused or rejected and if the patients are medically stable enough to undergo the procedure. Surgery may be indicated if noninvasive medical therapy, nasal CPAP, or OA fails to effectively treat OSA or is rejected by the patient.

Surgery is also indicated in patients who have a specific underlying abnormality that is causing the OSA. Three of 200 adults with OSA have a specific space-occupying lesion that causes an UA obstruction. Although surgical correction of such an abnormality (ie, tonsillectomy) can potentially cure OSA, most adult patients do not have such correctible lesions.

If the patient opts for surgery, ensure the following:

In some patients, tracheostomy or CPAP therapy is required in the perioperative period to ensure a safe airway.

For additional reading on surgery in OSA, the reader is referred to a 2005 pro-con debate in the Journal of Clinical Sleep Medicine by Powell ("Upper Airway Surgery Does Have a Major Role in the Treatment of Obstructive Sleep Apnea: ‘The Tail End of the Dog’") and Phillips ("Upper Airway Surgery Does Not Have a Major Role in the Treatment of Sleep Apnea").[195, 196]

Go to Surgical Approach to Snoring and Obstructive Sleep Apnea for complete information on this topic.

Anatomic considerations

Functional division of the pharynx into the retropalatal-oropharyngeal region (posterior to the soft palate) and the retrolingual-hypopharyngeal region (posterior to the vertical portion of the tongue) has been proposed. Obstruction in patients with SDB is classified into 3 types according to region. Type I is obstruction in only the retropalatal region. Type II is obstruction in both the retropalatal and retrolingual regions. Type III is obstruction in only the retrolingual region.

Choice of surgical procedure

A full listing of possible surgical procedures for OSA is available elsewhere.[197] Commonly performed procedures include the following:

Different surgical procedures have been proposed for patients with different levels of obstruction. UPPP may correct type I obstruction. GAHM may correct type III obstruction. MMO may correct obstruction at all levels.

AASM recommendations for surgical treatment of OSA

The ASDA published guidelines for the surgical treatment of OSA in 1995.[198]

The current position of the AASM on surgical therapy for OSA states the following:

Riley-Powell-Stanford surgical protocol

Because several sites of obstruction may be responsible, a systematic approach for selecting surgery has been developed.[199, 200] This is the Riley-Powell-Stanford surgical protocol designed in 1988. The protocol has 2 phases. Phase I consists of the UPPP and GAHM procedures, and phase II consists of the more complicated MMO procedure. Patients who are not adequately treated with phase I surgery are offered phase II surgery.

For phase I surgery, perform UPPP for patients with type I obstruction, GAHM for patients with type III obstruction, and simultaneous UPPP and GAHM for patients with type II obstruction. The overall success rate for phase I surgery is approximately 61%, although patients with severe OSA (RDI >60, lowest oxyhemoglobin saturation < 70%) have a success rate of only 42%.

Phase II surgery consists of MMO, in which the jaw is advanced anteriorly. With the phased protocol, the success rate has been in excess of 90% for phase II surgery.

Uvulopalatopharyngoplasty

UPPP is the most common surgical procedure performed for adults with OSA. It involves removal of the tonsils (if present), the uvula, the distal margin of the soft palate, and the redundant pharyngeal tissue, as well as reshaping of the soft tissues in the lateral pharyngeal walls.

AASM recommendations for UPPP state that "UPPP, with or without tonsillectomy, may be appropriate for patients with narrowing or collapse in the retropalatal region. Good preoperative evaluation does not guarantee surgical success; the effectiveness of the UPPP is variable, and the procedure should be considered when nonsurgical treatment options, such as CPAP, have been considered." It is important to note that enlarged adenoids and tonsils, in the adult OSA patient, are rarely a singular cause of OSA. As such, it is not a recommended surgery alone in the adult OSA patient.

The surgical success rate is not high with UPPP alone, approximately 50% when surgical success is defined as both 50% reduction in RDI and/or apnea index, and a postoperative RDI of less than 20 (or apnea index < 10). This rate is despite preselection of patients with type I obstruction by using imaging and endoscopic studies. This finding highlights the inadequacy of the methods available to identify sites of UA obstruction. This success rate, when compared with the potential complications of the surgery, has served to make the UPPP alone a rarely recommended procedure in the author’s center.

Complications from UPPP should be explained to patients in detail, as with all procedures; however, this is particularly true for those patients who use their voice to make a professional living (eg, singers, muscicians who play instruments that require maneuvers involving the areas where tissue will be removed).

Complications can include the following:

Silent apnea may result post-UPPP. Silent apnea refers to a condition in which the vibration of the tissues that caused snoring during airway collapse remains; thus, OSA persists but snoring does not. The decision to reevaluate OSA postsurgically should not depend on a postive report of snoring. If the patient still snores, however, this indicates that the surgery was not curative of obstructive sleep-related breathing disturbance (see the image below).



View Image

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occ....

Two studies showed that UPPP may make OSA worse, as it did in 31% of the patient population studied. Previous UPPP reduces the maximal level of pressure that patients who require CPAP therapy can tolerate. It may also compromise subsequent CPAP therapy by promoting mouth leaking. Uvulopalatopharyngoglossoplasty (UPPPG) is a modified UPPP with limited resection of the base of the tongue in which both the retropalatal and retrolingual regions of the UA are enlarged.

Genioglossus advancement with hyoid myotomy

In GAHM, the genioglossus muscle is repositioned anteriorly through an inferior mandibular osteotomy (genioglossus advancement). This maneuver places the pharyngeal muscles and the base of the tongue on tension and expands the airway. The hyoid is suspended to the superior edge of the larynx and fixed in this position, adding to the effect of genioglossus advancement.

Maxillomandibular osteotomy

In MMO, the midface, palate, and mandible are moved forward, increasing the space behind the tongue and increasing tension on the genioglossus muscle. This operation is more extensive than any of the others described. It is usually reserved for patients in whom other treatment modalities fail.

Tracheostomy

Tracheostomy bypasses the UA and is the most effective surgical procedure for treatment of OSA; it is virtually 100% effective. Unfortunately, tracheostomy is a disfiguring procedure and decreases the patient’s quality of life. Tracheostomy is now reserved for patients with severe OSA in whom other medical and surgical treatment modalities fail. Tracheostomy is also used for airway protection during UA reconstructive surgery.

Other surgical options

Laser-assisted uvulopalatoplasty is successful for reducing snoring in 90% of patients, but the success rate in patients with SDB is not clear. It may cause more scarring than UPPP, and it could potentially worsen apnea. Worsened OSA has been observed in the early postoperative period after laser-assisted uvulopalatoplasty. Laser-assisted uvulopalatoplasty is not recommended for the treatment of OSA until further data are available.

Laser midline glossectomy and lingualplasty are performed to enlarge the retrolingual region by using a laser to remove a portion of the posterior aspect of the tongue. The role of these procedures in the management of SDB has yet to be defined.

Nasal surgery includes septoplasty, turbinectomy, and polypectomy and may be useful as an adjunct to other procedures or to improve CPAP adherence. Nasal surgery by itself is rarely effective for the treatment of OSA.

Radiofrequency volumetric tissue reduction of soft palate

Recent interest has been generated in a new technique, pioneered by Powell and associates,[201] in which radiofrequency (RF) energy is used to ablate the soft palate. The US Food and Drug Administration (FDA) has approved this procedure for the treatment of snoring and OSA.

A midline soft palate submucosal scar is created by using a needle electrode inserted near the border of the hard palate and directing it toward the uvula. Pulses of RF energy are delivered, resulting in tissue necrosis and needle-tract fibrosis over subsequent weeks to months.

A study of 22 patients with mild SDB demonstrated reduced palatal tissue volume and improved symptoms in all subjects.[202] However, no data are available regarding improvement of RDI and oxyhemoglobin saturation. Follow-up over 12-18 months revealed that approximately 41% of patients who underwent RF volumetric reduction of the soft palate developed recurrent snoring. Evidence showed postsurgical improvement in the severity of esophageal pressure swings, indicating that this treatment may be useful in patients with UARS.

One study of RF volumetric reduction of the soft palate in 12 patients demonstrated success in treating snoring, but data regarding adequate treatment of SDB are lacking.[203] Data from large controlled studies are required before this technique can be recommended for the treatment of SDB. RF volumetric reduction appears to decrease morbidity compared with UPPP, laser-assisted uvulopalatoplasty, and lingualplasty.

Finally, animal studies of RF volumetric reduction of the tongue have shown volume reduction in tongue tissue after treatment. Results of human studies are pending.

Bariatric surgery

Bariatric surgery as therapy for OSA has been investigated in several nonrandomized, uncontrolled studies, with most showing a decrease in the AHI with weight loss. The 2006 practice parameter on medical therapies for OSAHS lists bariatric surgery as an option for OSA, although with limited evidence.[153]

Unfortunately, studies have not examined presurgery and postsurgery RDI or AHI using a design in which subjects were randomly assigned to a weight-loss surgery group and followed over time. At best, improvements in clinical symptoms have occurred after weight-loss surgery; however, again because no PSG data were available before or after weight-loss surgery and because subjects could not be randomly assigned to a weight-loss surgery group or control group, these data suggest that weight loss reduces OSA symptoms.

It is unknown whether this is a placebo effect, as objective reduction in the RDI or AHI as determined by the criterion standard of PSG, was not permitted by the human subjects committee.[204]

In a position paper on the treatment of OSA, the AASM stated that "[b]ariatric surgery should be considered as an adjunct to less invasive and rapidly active first-line therapies such as [positive airway pressure] for patients who have OSA and meet the currently published guidelines for bariatric surgery (Consensus). The remission rate for OSA two years after bariatric surgery, related to the amount of weight lost, is 40%, emphasizing the need for ongoing clinical follow-up of these patients."[205]

Guidelines for bariatric surgery have been published by the Society of American Gastrointestinal and Endoscope Surgeons (SAGES).[206]

Perioperative management of OSA is of special concern to anesthesiologists, and best practice papers have been published to address these concerns.[207]

Effectiveness

Factors that increase the likelihood of successful surgery include (1) lower AHI, (2) lower BMI, (3) the location of collapse (surgeries targeted specifically to collapse at either the nasopharynx or oropharynx improve outcome), (4) the degree of mandibular protrusion (better outcomes are achieved in patients with clear deficiencies), and (5) the presence of fewer comorbidities.

The success of surgical procedures for OSA depends on accurate identification of the site of obstruction in the UA. Modalities available for identifying the site of obstruction include lateral cephalometry, endoscopy, fluoroscopy, computed tomography (CT) scanning, and magnetic resonance imaging (MRI). The accuracy of these methods in identifying the sites of obstruction is not clear. Success rates for UPPP are only approximately 50% despite preselection of patients with type I obstruction.

Data regarding surgical therapy for OSA are mainly from case series. The phased protocol of Riley-Powell-Stanford holds promise for achieving cure in patients with OSA, but further data from controlled clinical trials are needed to decide its role in the overall management of OSA.

The success rates quoted are from select centers with surgeons highly skilled in these special procedures. These results cannot be extrapolated to the general population of patients with OSA. All patients undergoing surgery for treatment of OSA should undergo follow-up PSG.

Several studies have compared surgery with both CPAP and OAs. In one randomized study comparing temperature-controlled RF tissue ablation of the tongue with CPAP, CPAP was more effective at lowering the AHI but no differences were noted in functional outcome measures such as sleepiness at approximately 1 month of treatment.[208]

In a retrospective cohort study, UPPP was found to be associated with decreased mortality compared with CPAP[209] over a 3- to 5-year period of follow-up. Additionally, one long-term outcome study compared UPPP with OA therapy. In this study, 63% of the oral appliance subjects had a normal AHI at 4-year follow-up, compared with only 33% for the UPPP subjects.[210]

Management of Residual Sleepiness Despite Apparently Effective Treatment

Residual excessive daytime sleepiness (EDS) after apparently effective treatment with CPAP is a commonly encountered problem. An exact percentage of patients has not been determined but has been estimated at 5% in one study.[211] Residual EDS is generally considered present if the ESS score remains higher than 10 after treatment.

Some of these patients may not have been "optimally" treated; rather, they were put on a positive pressure setting which, during the sleep disorders center positive airway pressure study, is sufficient to correct OSA. They may not be optimally treated for a number of reasons that need to be considered first, before placing patients in this subgroup of patients.

Reasons for suboptimal OSA treatment may include the following:

If residual sleepiness after treatment is present, a series of questions must be asked to determine its etiology. The residual sleepiness should never be considered idiopathic until all questions have been answered satisfactorily. The algorithm used by the author can be found in the image below and the questions that follow it.



View Image

Approach to a patient with excessive daytime sleepiness after treatment with nasal continuous positive airway pressure.

See the list below:

If the above-mentioned potential causes of excessive sleepiness have been excluded, among others that the author may not have considered herein, use of stimulants to treat excessive sleepiness is indicated.

Several medications may be considered for treatment of residual sleepiness: the stimulants modafinil and armodafinil, or solriamfetol, a dopamine/norepinephrine reuptake inhibitor (DNRI). These agents are approved by the FDA for treating residual sleepiness despite optimal treatment of OSA using positive airway pressure therapy.

Modafinil seems most effective when used at the higher dose of 400 mg/d, whereas fatigue seems to be better treated with lower doses of the medication (100-200 mg/d).

If modafinil does not help at higher doses, the authors then consider armodafinil. Armodafinil reaches a peak plasma level nearly as quickly as modafinil and has a larger area under the curve for a given dose; additionally, the duration of action of armodafinil continues at the higher dosage throughout the day. Because of this action, armodafinil has more potency and most often requires only once-a-day dosing (taken in the morning for daytime workers and in the evening for nighttime workers).

FDA approval of modafinil was based on several studies carried out in this patient population.[213, 214, 215] The largest of these studies was a double-blind, randomized, placebo-controlled study in which subjects received either placebo or modafinil (200 mg/d in week 1, 400 mg/d in weeks 2-4) for 4 weeks.[214] . Subjects had an AHI of 15 or more, ESS of 10 or more, and CPAP use of 4 hours per night or more or 5-7 nights or more during 3 weeks of home monitoring.

One hundred fifty-seven patients were randomized (77 modafinil, 80 placebo), with 143 completing the study (66 modafinil, 77 placebo). The primary efficacy measures were the Epworth Sleepiness Score (ESS), daytime sleep latency based on multiple sleep latency test (MSLT) results, and CPAP use. Both the ESS and daytime sleep latency improved in the modafinil group. No difference was noted in CPAP use between groups.

The effectiveness of modafinil in this clinical situation has been confirmed by a randomized, double-blind study of modafinil versus placebo for 12 weeks, which showed that the efficacy of modafinil, as measured subjectively by the ESS and objectively by the maintenance of wakefulness test (MWT), does not change over an extended period (12 wk).[79]

One concern clinicians share with the use of modafinil (or other stimulants) in the management of OSA is whether improvement in alertness with the use of these agents may lead to noncompliance with CPAP therapy. This is an important concern, because stimulants do not control the SDB, resulting in worsening symptom control and potentially increasing the risk of cardiovascular morbidity.

Fortunately, this does not appear to be a major problem at present. The 2 largest trials did not show a decrease in CPAP usage with modafinil.[214, 79] However, decreased CPAP usage was noted in the smaller randomized study of modafinil[213] and in an open-label extension trial.[215] Therefore, if a patient is prescribed a stimulant, compliance with CPAP must be closely monitored.

More data are needed to increase assurance that use of stimulants does not lead to noncompliance. In the authors’ experience, it is unlikely that stimulant use is sufficient to correct the severe sleepiness OSA patients experience; hence, both positive airway pressure treatment and stimulant use are preferred by patients.

Approval of solriamfetol for excessive daytime sleepiness in adults with OSA was based on the TONES 3 randomized controlled trial. A total of 476 patients with OSA were randomized to receive solriamfetol 37.5 mg, 75 mg, or 150 mg, or placebo, once daily. Coprimary endpoints (Maintenance of Wakefulness Test sleep latency and Epworth Sleepiness Scale score) were met at all solriamfetol doses (P< .05), with dose-dependent effects observed at week 1 maintained over the 12-week study duration. All doses except 37.5 mg resulted in higher percentages of participants reporting improvement on Patient Global Impression of Change (key secondary endpoint; I < .05).[216]

The use of stimulant medications (ie, modafinil, armodafinil) or a DNRI (ie, solriamfetol) should be reserved for patients optimally treated with CPAP and who remain sleepy. However, there is not yet a consensus on the role of stimulant medications to enhance alertness, and research in nonoptimally treated OSA patients has not been performed to determine to what degree, if any, subjective and objective changes occur when the medications are used for OSA patients not treated ideally with CPAP.

Prevention of Obstructive Sleep Apnea

Patients should restrict their body positions during sleep. SDB is worse in the supine position, and some patients have apnea only in this position. Preventing the patient from assuming the supine position by using devices such as a snore ball (eg, a tennis ball sewn onto the back of the patient’s pajamas) or a gravity-activated position monitor may be useful. However, these devices are cumbersome and appear to benefit only those patients with mild OSA.

Patients with marked obesity may benefit from sleeping in an upright position. Additionally, the FDA has approved a specially designed pillow (PillowPositive) for the treatment of snoring and mild OSA, which maintains the patient’s head and neck position during sleep to optimize UA patency.

Patients should avoid smoking. Smoking increases the risk of snoring and apnea. Smoking cessation appears to decrease the risk. Individuals who smoke are also more likely than those who do not smoke to report problems with going to sleep, maintaining sleep, and daytime somnolence.

Patients should avoid drinking alcohol and using other sedatives known to make apnea worse. Finally, patients should avoid sleep deprivation.

Consultations

All patients with signs or symptoms of OSA should be referred to a sleep disorders center for an evaluation by a sleep physician and a PSG study. A comprehensive sleep evaluation is recommended because as many as 25% of sleep patients have more than one sleep disorder, many of which are only identified as a result of a consultation with a sleep specialist.

Any patient with loud habitual snoring and any other feature of OSA who is being considered for surgery should be referred for a sleep study prior to surgery. This is important to rule out OSA because the surgery is likely to correct the snoring but may not correct the apneas or hypopneas, which are associated with other morbidities.

Patients should also undergo complete evaluation by a dental professional, who should be experienced in OA therapy and should work in close collaboration with the sleep disorders specialist.

Long-Term Monitoring

Follow-up

Once diagnosed with OSA and started on nasal CPAP, patients require regular follow-up with a sleep specialist. Most patients are seen within 2 months of initiating CPAP to determine if it has been effective in alleviating symptoms (eg, daytime sleepiness is substantially reduced or eliminated), to troubleshoot problems preventing regular use of the CPAP, and to reinforce the importance of daily use.

Further follow-up depends on whether the CPAP has been effective.

A study by Kuna et al assessed home monitoring and determined that functional outcome and treatment adherence in patients evaluated using a home testing algorithm was not clinically inferior to the results found among patients receiving standard, in-laboratory PSG.[217]

Assessment of driving and flying risk

Assess the risk of driving in any patient with OSA. Criteria that increase this risk are as follows:

Immediately warn patients at highest risk of the potential dangers of driving while sleepy—specifically, of the potential personal and social risk. Provide additional counseling depending on other risk factors (eg, occupation). Advise patients to not drive until their OSA is treated adequately. Provide additional counseling to family members as appropriate, and help patients explore alternatives to driving if they are unaware of their sleepiness or if they are unwilling to acknowledge their increased risk.

Document in writing any warnings, concerns, and/or recommendations given to the patient. This documentation reinforces the importance of the message to the patient and helps reduce the risk of legal liability for medical personnel.

Whether and under what circumstances patients with sleep apnea should be reported to the licensing authority depend on the laws of the state. Those who take care of patients with OSA must be aware of state statutes or regulations regarding reporting of high-risk drivers.

Laws regarding impaired drivers, including those with OSA, vary from state to state. In some states, the clinician is obligated to report patients under specific conditions (ie, mandatory reporting statute), whereas other states permit reporting but do not require it (ie, permissive reporting statute). Mandatory statutes take 1 of the 2 following approaches:

Each clinician is obligated to adhere to the requirements of the law in the specific state of practice, even if those laws do not reflect sound public policy or medical evidence. Irrespective of whether statutory reporting is required, clinicians may be liable for damages if a patient with obstructive sleep apnea injures himself or herself or someone else while driving.

American Thoracic Society guidelines on reporting of patients to the appropriate state authorities are as follows[74] :

Categorical reporting may be most appropriate in the context of occupational licenses, but this is arguable. At a minimum, the threshold for suspecting an increased driving risk due to sleepiness should be low given the increased hazard.

The US Department of Transportation convened a group of respiratory experts at its Conference on Pulmonary/Respiratory Disorders in Commercial Drivers in September 1990. The group recommends that operators with suspected sleep apnea should not be medically qualified for commercial vehicle operation “until the diagnosis has been eliminated or accurately treated.”

A US Federal Aviation Administration specification letter entitled “Sleep Apnea Evaluation Specifications” states that the complications of OSA present a risk to flying safety and recommends an initial workup, acceptable treatments, and follow-up for pilots being evaluated for OSA.

Medication Summary

Pharmacologic therapy is generally not a part of the primary treatment recommendations. Acetazolamide, medroxyprogesterone, fluoxetine, and protriptyline have been used to treat obstructive sleep apnea (OSA); however, these medications are not recommended. Modafinil is approved by the US Food and Drug Administration (FDA) for use in patients who have residual daytime sleepiness despite optimal use of CPAP. The most improvement has been seen in patients who have taken modafinil at doses of 200-400 mg/d. Armodafinil, the R-enantiomer of modafinil, is also now FDA approved for use in these patients.

Solriamfetol, a dopamine/norepinephrine reuptake inhibitor (DNRI), was approved in 2019 and is indicated to improve wakefulness in patients with excessive daytime sleepiness who have OSA.

The American Academy of Sleep Medicine (AASM), in a practice parameter and review of medical therapies for OSA,[153, 218] listed the use of protriptyline as a guideline (patient care strategy based on level 2 or 3 evidence).[218] The use of modafinil was recommended for the treatment of residual sleepiness in persons with OSA and was considered a standard treatment (generally accepted patient care strategy with level 1 or excellent level 2 evidence).

The parameters state as standards that selective serotonin reuptake inhibitors, methylxanthines, and estrogen replacement therapy should not be considered for the treatment of OSA.

Modafinil (Provigil)

Clinical Context:  The mechanism of action of modafinil in wakefulness is unknown. It has wake-promoting actions similar to sympathomimetic agents. It is indicated as adjunctive treatment to standard therapy for OSA/hypopnea syndrome to improve wakefulness in patients with excessive sleepiness.

Armodafinil (Nuvigil)

Clinical Context:  Armodafinil is the R-enantiomer of modafinil (mixture of R- and S-enantiomers). It elicits wake-promoting actions similar to sympathomimetic agents, although its pharmacologic profile is not identical to those of sympathomimetic amines. In vitro, armodafinil binds dopamine transporters and inhibits dopamine reuptake. It is not a direct- or indirect-acting dopamine receptor agonist. It is indicated to improve wakefulness in individuals with excessive sleepiness associated with narcolepsy, OSA, or shift-work sleep disorder.

Class Summary

Central nervous system (CNS) stimulants may be used to promote daytime wakefulness in sleep apnea patients who have residual daytime sleepiness despite optimal use of continuous positive airway pressure (CPAP). They treat fatigue without interfering with normal sleep architecture. Modafinil and armodafinil are indicated for OSA.

Solriamfetol (Sunosi)

Clinical Context:  Solriamfetol is a dopamine/norepinephrine reuptake inhibitor (DNRI). It is indicated to improve wakefulness in adults with excessive daytime sleepiness associated with OSA.

Class Summary

The mechanism of action by which solriamfetol improves wakefulness in patients with excessive daytime sleepiness associated with narcolepsy is unclear, but is thought to be mediated through its inhibition of dopamine/norepinephrine reuptake. 

What is obstructive sleep apnea (OSA)?How do symptoms of obstructive sleep apnea (OSA) begin?What are nocturnal symptoms of obstructive sleep apnea (OSA)?What are the daytime symptoms of obstructive sleep apnea (OSA)?Which physical findings are characteristic of obstructive sleep apnea (OSA)?What should be evaluated in all patients with obstructive sleep apnea (OSA)?Which physical findings suggest obstructive sleep apnea (OSA)?How is obstructive sleep apnea (OSA) diagnosed?What is the role of lab testing in the diagnosis of obstructive sleep apnea (OSA)?When is a thyrotropin test indicated in the evaluation of obstructive sleep apnea (OSA)?What are the AASM guidelines for polysomnography in the diagnosis of obstructive sleep apnea (OSA)?How does severity of obstructive sleep apnea affect treatment options?What are the conservative measures used to manage or prevent obstructive sleep apnea (OSA)?What are mechanical measures used in the treatment of obstructive sleep apnea (OSA)?What is the role of medications in the treatment of obstructive sleep apnea (OSA)?What are the surgical options for treatment of obstructive sleep apnea (OSA)?What is obstructive sleep apnea (OSA)?What are manifestations of obstructive sleep apnea (OSA)?What are the symptoms of obstructive sleep apnea (OSA)?What is characteristic of patients with obstructive sleep apnea (OSA)?What are significant complications of obstructive sleep apnea (OSA)?Which breathing events are evaluated in patients with obstructive sleep apnea (OSA)?What is the AASM definition of apnea?What are the AASM guidelines for scoring hypopneas in the evaluation of obstructive sleep apnea (OSA)?What is the role of respiratory effort–related arousal (RERA) measurement in the evaluation of obstructive sleep apnea (OSA)?How are respiratory effort–related arousals (RERAs) measured in the evaluation of obstructive sleep apnea (OSA)?How is obstructive sleep apnea (OSA) distinguished from central sleep apnea (CSA)?What is a sleep-related breathing disorder (SRBD) continuum?What was the initial description of sleep-related breathing disorder (SRBD) continuum?How does disease progress on the sleep-related breathing disorder (SRBD) continuum?What is the disease progression of untreated obstructive sleep apnea (OSA)?What causes obstructive sleep apnea (OSA)?What is the role of transmural pressure in the pathogenesis of obstructive sleep apnea (OSA)?Where does upper airway (UA) obstruction occur in obstructive sleep apnea (OSA)?What is the role of anatomy in the pathogenesis of obstructive sleep apnea (OSA)?What is the role of neuromuscular activity in the pathogenesis of obstructive sleep apnea (OSA)?What is the role of central breathing instability in the pathogenesis of obstructive sleep apnea (OSA)?Which static factors are involved in the pathogenesis of obstructive sleep apnea (OSA)?Which dynamic factors are involved in the pathogenesis of obstructive sleep apnea (OSA)?What is the role of the Bernoulli effect in the pathophysiology of obstructive sleep apnea (OSA)?Why is obesity a risk factor for obstructive sleep apnea (OSA)?What is the epidemiologic distribution for obstructive sleep apnea (OSA)?What are the characteristics of apnea clusters in obstructive sleep apnea (OSA)?What is the underlying mechanism for apnea clusters in obstructive sleep apnea (OSA)?What is the role of oxygen desaturation in the pathophysiology of obstructive sleep apnea (OSA)?What are the clinical implications of oxygen desaturation in patients with obstructive sleep apnea (OSA)?How is obstructive sleep apnea (OSA) linked to cardiovascular disease?What are the nonstructural risk factors for obstructive sleep apnea (OSA)?Which factors are involved in the etiology of obstructive sleep apnea (OSA)?Which etiological structural factors are related to craniofacial bony anatomy in obstructive sleep apnea (OSA)?Which etiological structural factors are related to nasal obstruction in obstructive sleep apnea (OSA)?When should craniofacial abnormalities be considered in the etiology of obstructive sleep apnea (OSA)?What is the basis of craniofacial risk factors for obstructive sleep apnea (OSA)?What are the differences in cranial and facial indices in patients with obstructive sleep apnea (OSA)?What is the role of familial factors in the etiology of obstructive sleep apnea (OSA)?Which conditions are associated with obstructive sleep apnea (OSA)?What is the etiological relationship between hypothyroidism and obstructive sleep apnea (OSA)?Which neurologic syndromes are associated with obstructive sleep apnea (OSA)?What is the etiological relationship between obstructive sleep apnea (OSA) and cerebrovascular disease?What is the etiological relationship between acromegaly and obstructive sleep apnea (OSA)?Which environmental exposures are associated with the development of obstructive sleep apnea (OSA)?What is the role of genetics in the etiology of obstructive sleep apnea (OSA)?Which gene variants have been associated with obstructive sleep apnea (OSA)?What is the role of C-reactive protein (CRP) in the etiology of obstructive sleep apnea (OSA)?What is the role of gene glial cell line-derived neurotrophic factor (GDNF) in the etiology of obstructive sleep apnea (OSA)?What is the role of the 5HT2A gene in the etiology of obstructive sleep apnea (OSA)?What criteria are used to identify genetic associations with obstructive sleep apnea (OSA)?What is the prevalence of sleep-disordered breathing (SDB) in the US?What is the prevalence of obstructive sleep apnea (OSA) in the US?What is the prevalence of obstructive sleep apnea (OSA) in children in the US?What is the global prevalence of obstructive sleep apnea (OSA)?How does the incidence of obstructive sleep apnea (OSA) vary by age?How does the prevalence of obstructive sleep apnea (OSA) vary by sex?How does menopause affect the prevalence of obstructive sleep apnea (OSA) among women?How do the findings of obstructive sleep apnea (OSA) vary by sex?What are the racial predilections of obstructive sleep apnea (OSA)?What is the short-term prognosis of obstructive sleep apnea (OSA)?What is the long-term prognosis of obstructive sleep apnea (OSA)?What is the mortality rate for sleep apnea (OSA)?What were the results of the Sleep Heart Health Study on the effect of obstructive sleep apnea (OSA) on mortality?In which age groups is the obstructive sleep apnea (OSA) mortality risk greatest?What is the association between obstructive sleep apnea (OSA) and cardiovascular death?How does continuous positive airway pressure (CPAP) mitigate the mortality risk in obstructive sleep apnea (OSA)?At what time of day are patients with obstructive sleep apnea (OSA) at highest risk of sudden death?What is the relationship between obstructive sleep apnea (OSA) and pulmonary hypertension?What cardiovascular abnormality is caused by oxygen desaturation in obstructive sleep apnea (OSA)?What is the relationship between obstructive sleep apnea (OSA) and cardiovascular disease?What is the relationship between obstructive sleep apnea (OSA) and motor vehicle accidents?What can clinicians predict if a patient with obstructive sleep apnea (OSA) is at higher risk for motor vehicle accidents?What scores on the Epworth Sleepiness Scale (ESS) indicate an increased risk for motor vehicle accidents due to obstructive sleep apnea (OSA)?What is the increased risk for auto accidents in patients with obstructive sleep apnea (OSA)?How accurate is simulator performance in predicting risk of auto accidents in patients with obstructive sleep apnea (OSA)?What is the effect of treatment of obstructive sleep apnea (OSA) on motor vehicle accident risk?What are the crash rates among patients with obstructive sleep apnea (OSA)?What are the guidelines regarding driving for the average patient with obstructive sleep apnea (OSA)?What information about obstructive sleep apnea (OSA) should patients be given?How long after the onset of symptoms are patients typically evaluated for obstructive sleep apnea (OSA)?What are the nocturnal symptoms of obstructive sleep apnea (OSA)?What are the daytime symptoms of obstructive sleep apnea (OSA)?What is the most common and difficult symptom of obstructive sleep apnea (OSA) to treat?What is the role of the Epworth Sleepiness Scale (ESS) in the evaluation of obstructive sleep apnea (OSA)?How does continuous positive airway pressure (CPAP) affect excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA)?How do patients characterize excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA)?How is daytime functioning affected in obstructive sleep apnea (OSA)?What are the typical findings of a general physical exam in obstructive sleep apnea (OSA)?Which physical findings are characteristic of obstructive sleep apnea (OSA)?What is the role of body mass index (BMI) in obstructive sleep apnea (OSA)?What is the association between neck circumference and obstructive sleep apnea (OSA)?How is the Mallampati score used in the evaluation of obstructive sleep apnea (OSA)?What is the significance of a history of disruptive snoring in the evaluation for obstructive sleep apnea (OSA)?What is the role of the patient’s significant other in the evaluation of obstructive sleep apnea (OSA)?What sex-related differences should be considered in the evaluation of obstructive sleep apnea (OSA)?How is the mnemonic STOP used in the evaluation of obstructive sleep apnea (OSA)?How is the mnemonic BANG used to in the evaluation of obstructive sleep apnea (OSA)?What is indicated if the criteria for both the STOP and BANG questionnaires are met in the evaluation of obstructive sleep apnea (OSA)?What is the accuracy of the STOP-BANG questionnaire for the screening of obstructive sleep apnea (OSA)?What tool is available for preoperative predictions of obstructive sleep apnea (OSA)?Which organization released an expert review of obstructive sleep apnea (OSA) and cardiovascular disease?How does obstructive sleep apnea (OSA) lead to cardiovascular disease?What is the role of obstructive sleep apnea (OSA) in the pathogenesis of cardiovascular diseases?When should obstructive sleep apnea (OSA) be evaluated in patients with cardiovascular disease?What is the prevalence of systemic hypertension in obstructive sleep apnea (OSA)?How does severity of obstructive sleep apnea (OSA) affect the development of hypertension?What did the Sleep Heart Study reveal about the relationship between hypertension and obstructive sleep apnea (OSA)?How does continuous pressure (CPAP) treatment for obstructive sleep apnea (OSA) affect blood pressure?How is hypertension managed in obstructive sleep apnea (OSA)?How does decreased CPAP affect BP in patients with obstructive sleep apnea (OSA)?How many hours of CPAP use is required to reduce BP in obstructive sleep apnea (OSA)?What is the role of antihypertensive medications in the treatment of obstructive sleep apnea (OSA)?What is the association between atherosclerosis and obstructive sleep apnea (OSA)?What is the association between obstructive sleep apnea (OSA) and congestive heart failure?What is the association between obstructive sleep apnea (OSA) and cardiac arrhythmias?What is the association between myocardial ischemia and infarction and obstructive sleep apnea (OSA)?What is the association between stroke and obstructive sleep apnea (OSA)?What is the association between metabolic syndrome and obstructive sleep apnea (OSA)?What is the effect of obstructive sleep apnea (OSA) on glucose levels and insulin resistance?How does oxygen desaturation in obstructive sleep apnea (OSA) correlate with insulin resistance?What is the effect of obstructive sleep apnea (OSA) on CPR levels?What is the effect of obstructive sleep apnea (OSA) on the production of nitric oxide?What abnormalities of metabolic syndrome decreased by continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA)?What is the association between obstructive sleep apnea (OSA) and diabetes?What is the presentation of obstructive sleep apnea (OSA) in elderly patients?What are the signs and symptoms of obstructive sleep apnea (OSA) in children?What is the standard therapy for children with obstructive sleep apnea (OSA)?What are complications of obstructive sleep apnea (OSA) during pregnancy?What are the risk factors for obstructive sleep apnea (OSA) in long-distance truck drivers?What are other risks associated with obstructive sleep apnea (OSA)?When should narcolepsy be consider in the diagnosis of obstructive sleep apnea (OSA)?Which indices are commonly used to assess sleep disordered breathing (SDB) in patients with obstructive sleep apnea (OSA)?What are the Centers for Medicare & Medicaid Services diagnostic criteria for obstructive sleep apnea (OSA)?What are the AASM diagnostic criteria for obstructive sleep apnea (OSA)?How are sleep centers accredited for the diagnosis of obstructive sleep apnea (OSA)?Which conditions should be included in the differential diagnoses of obstructive sleep apnea (OSA)?What are the differential diagnoses for Obstructive Sleep Apnea (OSA)?What are the ACP guidelines for the evaluation of obstructive sleep apnea (OSA)?What guidelines are available on the use of home sleep testing in the evaluation of obstructive sleep apnea (OSA)?Which imaging studies are used to identify the site of obstruction in patients with obstructive sleep apnea (OSA)?What is the role of pulmonary function tests (PFTs) in the diagnosis of obstructive sleep apnea (OSA)?What is the role of routine lab testing in the diagnosis of obstructive sleep apnea (OSA)?What is respiratory event–related arousal (RERA) in obstructive sleep apnea (OSA)?What are the AASM recommendations for the use of portable monitors for the diagnosis of obstructive sleep apnea (OSA)?What is the role of polysomnography (PSG) in the diagnosis of obstructive sleep apnea (OSA)?What guidelines exist for the use of diagnostic polysomnography (PSG) for obstructive sleep apnea (OSA)?What are the AASM guidelines for the performance of polysomnography (PSG) to diagnose obstructive sleep apnea (OSA)?What is the definition of obstructive apnea?What is the definition of central apnea?What is the definition of mixed apnea?What is hypopnea in obstructive sleep apnea (OSA)?What is the importance of arousals in the evaluation of obstructive sleep apnea (OSA)?Which polysomnography (PSG) findings are characteristic of obstructive sleep apnea (OSA)?How is the apnea-hypopnea index (AHI) used in the diagnosis of obstructive sleep apnea (OSA)?How is split-night polysomnography (PSG) used in the diagnosis of obstructive sleep apnea (OSA)?When should polysomnography (PSG) be repeated in the management of obstructive sleep apnea (OSA)?What is the validity of home testing for the diagnosis of obstructive sleep apnea (OSA)?What are the levels of portable monitors for the diagnosis of obstructive sleep apnea (OSA)?What is the efficacy of level 3 portable monitors for the diagnosis of obstructive sleep apnea (OSA)?What are the efficacy of at-home diagnosis and treatment of obstructive sleep apnea (OSA)?What is the two-stage model to identify obstructive sleep apnea (OSA) in primary care?What are the outcomes for level 3 home testing in the diagnosis of obstructive sleep apnea (OSA)?What is efficacy of home obstructive sleep apnea (OSA) testing?How does a disposable skin patch compare to polysomnography (PSG) in the detection of obstructive sleep apnea (OSA)?What is the role of sleepiness and alertness measurement in obstructive sleep apnea (OSA)?What is the role of the multiple sleep latency test (MSLT) in the diagnosis of obstructive sleep apnea (OSA)?What is the role of the maintenance of wakefulness test (MWT) in the management of obstructive sleep apnea (OSA)?What is the basis for treatment selection in obstructive sleep apnea (OSA)?What are the nonsurgical options for obstructive sleep apnea (OSA)?What are the benefits of weight reduction in patients with sleep disordered breathing (SDB) and obstructive sleep apnea (OSA)?What increases the risk of relapse of obstructive sleep apnea (OSA) after surgery?What are the mechanical measures for the treatment of obstructive sleep apnea (OSA)?When are oral appliances (OAs) used in the treatment of obstructive sleep apnea (OSA)?What is the role of pharmacologic therapy in the treatment of obstructive sleep apnea (OSA)?What are treatments options for obstructive sleep apnea (OSA)?What should be included in the follow-up of CPAP treatment for obstructive sleep apnea (OSA)?How is the concept of the sleep-related breathing disorder (SRBD) continuum used in the treatment of obstructive sleep apnea (OSA)?How is snoring differentiated from CPAP mask leak in obstructive sleep apnea (OSA)?What are the indications for upper airway (UA) corrective surgery in the treatment of obstructive sleep apnea (OSA)?What is the standard of care for obstructive sleep apnea (OSA)?How are continuous positive airway pressure (CPAP) devices used to treat obstructive sleep apnea (OSA)?How does continuous positive airway pressure (CPAP) work in obstructive sleep apnea (OSA)?What are the treatment recommendations severe sleep-disordered breathing (SDB)?What are the Medicare criteria for continuous positive airway pressure (CPAP) to treat obstructive sleep apnea (OSA)?What are auto-titrating devices for the treatment of obstructive sleep apnea (OSA)?What are the AASM guidelines for use of auto titrating devices in the management of obstructive sleep apnea (OSA)?Which obstructive sleep apnea (OSA) symptoms are resolved with use of continuous positive airway pressure (CPAP)?What improvements are likely following continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA)?Which comorbidity risks are decreased following use of continuous positive airway pressure (CPAP) to treat obstructive sleep apnea (OSA)?What are benefits of continuous positive airway pressure (CPAP) for obstructive sleep apnea?How are neurocognitive symptoms managed in obstructive sleep apnea (OSA)?What are the effects of stopping continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA)?What are the benefits of using continuous positive airway pressure (CPAP) as treatment for obstructive sleep apnea (OSA)?What are indicators of poor adherence of continuous positive adherence for the treatment of obstructive sleep apnea (OSA)?How is compliance with continuous positive airway pressure (CPAP) measured during treatment for obstructive sleep apnea (OSA)?How many hours of use is needed for continuous positive airway pressure (CPAP) to render a positive effect in obstructive sleep apnea (OSA)?When are patients considered compliant for the treatment of obstructive sleep apnea (OSA) using continuous positive airway pressure (CPAP)?How quickly is continuous positive airway pressure (CPAP) compliance determined in the treatment of obstructive sleep apnea (OSA)?What is the significance of long-term continuous positive airway pressure (CPAP) compliance in the treatment of obstructive sleep apnea (OSA)?How has continuous positive airway pressure (CPAP) adherence in obstructive sleep apnea (OSA) been assessed?What is the effect on compliance of flexible pressure delivery of positive airway pressure (PAP) in obstructive sleep apnea (OSA)?What is the effect of split-night polysomnography (PSG) on CPAP adherence in obstructive sleep apnea (OSA)?What are possible reasons for noncompliance with continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA)?Which interventions are used to improve continuous positive airway pressure (CPAP) compliance in obstructive sleep apnea (OSA)?What are the benefits of patient education with sleep specialists for obstructive sleep apnea (OSA)?What are the benefits of pressure-relief continuous positive airway pressure (CPAP) in the treatment of obstructive sleep apnea (OSA)?Which factors are likely to increase adherence to CPAP for obstructive sleep apnea (OSA)?What are complications of continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea (OSA)?What are mask-related problems associated with continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea (OSA)?What are nasal problems associated with continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea (OSA)?What are patient complaints associated with continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA)?What is the Medicare and Medicaid coverage for continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea (OSA)?Positive results from which clinical assessments indicate a diagnosis of obstructive sleep apnea (OSA)?How is bilevel positive airway pressure (BiPAP) therapy used in the treatment of obstructive sleep apnea (OSA)?What is the role of inspiratory and expiratory pressures in bilevel positive airway pressure (BiPAP) therapy for obstructive sleep apnea (OSA)?When is bilevel positive airway pressure (BiPAP) therapy indicated for obstructive sleep apnea (OSA)?How does compliances with bilevel positive airway pressure (BiPAP) compare to continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA)?How do oral appliances (OAs) work for the treatment of obstructive sleep apnea (OSA)?How are oral appliances (OAs) designed for the treatment of obstructive sleep apnea (OSA)?Which oral appliance (OA) devices are used for the treatment of obstructive sleep apnea (OSA)?What are the AASM guidelines for the use of oral appliances (OAs) in obstructive sleep apnea (OSA)?When is oral appliance (OA) therapy indicated for obstructive sleep apnea (OSA)?What is included in oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What is the role of apnea-hypopnea index (AHI) in oral appliance (OA) therapy for obstructive sleep apnea (OSA)?Which factors influence the benefit of oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What are the contraindications for oral appliance (OA) treatment for obstructive sleep apnea (OSA)?What affect does oral appliance (OA) therapy have on the apnea-hypopnea index (AHI) in obstructive sleep apnea (OSA)?Which biochemical factors are responsible for the effectiveness of oral appliances (OAs) in obstructive sleep apnea (OSA)?What is the effect on the lateral pharyngeal walls from oral appliances (OAs) for obstructive sleep apnea (OSA)?What is the treatment goal for oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What are the key variables in oral appliance (OA) therapy efficacy for obstructive sleep apnea (OSA)?What is the role of mandibular repositioning in oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What were the findings of an AASM review of oral appliance (OA) therapy for obstructive sleep apnea (OSA)?How do outcomes with oral appliance (OA) therapy compare with nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA)?What are benefits of oral appliance (OA) therapy for the treatment of obstructive sleep apnea (OSA)?What is the difference in efficacy between oral appliance (OA) therapy and uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea (OSA)?What are limitations to the use of oral appliances (OAs) for the treatment of obstructive sleep apnea (OSA)?What is the benefit of the titration approach in oral appliance (OA) therapy for obstructive sleep apnea (OSA)?Why is further work on titration required for oral appliance (OA) therapy of obstructive sleep apnea (OSA)?What are the adherence rates for oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What is the role of tongue-retaining devices (TRD) in the treatment of obstructive sleep apnea (OSA)?What is the cause for the decline of adherence to oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What are the adverse effects of oral appliance (OA) devices for the treatment of obstructive sleep apnea (OSA)?How are the adverse effects of oral appliance (OA) devices assessed in patients with obstructive sleep apnea (OSA)?How are multiple polysomnography (PSG) studies used in the management of oral device therapy for obstructive sleep apnea (OSA)?Why is long-term follow-up needed for oral appliance (OA) therapy in obstructive sleep apnea (OSA)?What are the limitations of adherence data for oral appliance (OA) therapy of obstructive sleep apnea (OSA)?What are complications oral appliance (OA) therapy for obstructive sleep apnea (OSA)?How is cost a barrier to oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What factors may limit the use of oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What does the ASDA advocate regarding the use of oral appliance (OA) therapy for obstructive sleep apnea (OSA)?What is the role of surgical correction of the upper airway (UA) for treatment of obstructive sleep apnea (OSA)?When is surgical care indicated for obstructive sleep apnea (OSA)?What are the prerequisites of surgical care for obstructive sleep apnea (OSA)?What is required perioperatively to ensure a safe airway during surgery for obstructive sleep apnea (OSA)?Where can additional information on surgery in obstructive sleep apnea (OSA) be found?What are the anatomic considerations for surgical treatment of obstructive sleep apnea (OSA)?What are the commonly performed surgical procedures for treatment of obstructive sleep apnea (OSA)?What are the indications for the specific surgical procedures for obstructive sleep apnea (OSA)?Who published guidelines for the surgical treatment of obstructive sleep apnea (OSA)?What is the position of the AASM) on surgical therapy for obstructive sleep apnea (OSA)?What is the approach to surgery selection for the treatment of obstructive sleep apnea (OSA)?What is phase I surgery for the treatment of obstructive sleep apnea (OSA)?What is phase II surgery for the treatment of obstructive sleep apnea (OSA)?What is the most common surgical procedure for obstructive sleep apnea (OSA)?What are the AASM recommendations for uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea (OSA)?What is the surgical success rate for uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea (OSA)?Which complications from uvulopalatopharyngoplasty (UPPP) are particularly significant for singers and musicians?What are the complications of uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea (OSA)?What is silent apnea in obstructive sleep apnea (OSA)?What are the disadvantages to uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea (OSA)?How is genioglossus advancement with hyoid myotomy (GAHM) used for the treatment of obstructive sleep apnea (OSA?)How is maxillomandibular osteotomy (MMO) used for the treatment of obstructive sleep apnea (OSA)?How is tracheostomy used for the treatment of obstructive sleep apnea (OSA)?What is the role of lasers in the treatment of obstructive sleep apnea (OSA)?What is the role of radiofrequency (RF) energy in the treatment of obstructive sleep apnea (OSA)?How is radiofrequency (RF) energy used in the treatment of obstructive sleep apnea (OSA)?What is the efficacy of radiofrequency (RF) energy treatment for obstructive sleep apnea (OSA)?What is the role of bariatric surgery in the treatment of obstructive sleep apnea (OSA)?What are the risks of bariatric surgery for obstructive sleep apnea (OSA)?What are the AASM guidelines for use of bariatric surgery in the treatment of obstructive sleep apnea (OSA)?What are the factors that increase the likelihood of successful surgery for obstructive sleep apnea (OSA)?What factor increases the likelihood of success for surgical treatment of obstructive sleep apnea (OSA)?Where have data been found regarding success rates for surgical therapy of obstructive sleep apnea (OSA)?How does surgery compare to other forms of treatment for obstructive sleep apnea (OSA)?How prevalent is residual EDS following treatment of obstructive sleep apnea (OSA)?What causes suboptimal treatment of obstructive sleep apnea (OSA)?How is the etiology of residual EDS in obstructive sleep apnea (OSA) determined?What questions are used to determine if residual sleepiness is idiopathic in obstructive sleep apnea (OSA)?Which medications should be considered for the treatment of residual sleepiness in obstructive sleep apnea (OSA)?How are medications administered in the treatment of residual sleepiness in patients with obstructive sleep apnea (OSA)?What was the evidence for FDA approval of modafinil for residual sleepiness in obstructive sleep apnea (OSA)?What is the efficacy of modafinil for residual sleepiness in obstructive sleep apnea (OSA)?What is the effectiveness of modafinil for residual sleepiness in obstructive sleep apnea (OSA)?What are the concerns with using modafinil to treat residual sleepiness in obstructive sleep apnea (OSA)?When are stimulants indicated in the treatment of obstructive sleep apnea (OSA)?What are the prevention measures for obstructive sleep apnea (OSA)?What activity modifications are helpful in the management of obstructive sleep apnea (OSA)?Which specialists should be consulted in the diagnosis and management of obstructive sleep apnea (OSA)?What monitoring is required for management of obstructive sleep apnea (OSA)?What is the basis for follow-up in patients with obstructive sleep apnea (OSA)?How frequently should patients with obstructive sleep apnea (OSA) be seen if continuous positive airway pressure (CPAP) is effective?How frequently should patients with obstructive sleep apnea (OSA) be seen if continuous positive airway pressure (CPAP) is not effective?When are repeat diagnostic procedures indicated for obstructive sleep apnea (OSA)?What is the difference in treatment adherence between at-home testing and in-lab treatment for obstructive sleep apnea (OSA)?Which factors increase the risk of driving in patients with obstructive sleep apnea (OSA)?What are the precautions against driving for patients with obstructive sleep apnea (OSA)?What should be documented in the follow-up of patients with obstructive sleep apnea (OSA)?What are the guidelines for reporting patients with obstructive sleep apnea (OSA)?What are the laws regarding impaired drivers, including those with obstructive sleep apnea (OSA)?What are the ATS guidelines on reporting of patients with obstructive sleep apnea (OSA) to the appropriate state authorities?When is categorical reporting of patients with obstructive sleep apnea (OSA) appropriate?What does the US Department of Transportation recommend for the driving status of persons with obstructive sleep apnea (OSA)?What does the US Federal Aviation Administration recommend for pilots with obstructive sleep apnea (OSA)?What is the role of medications in the treatment of obstructive sleep apnea (OSA)?What are the recommendations of the AASM for use of medications in the treatment of obstructive sleep apnea (OSA)?Which medications in the drug class CNS stimulants are used in the treatment of Obstructive Sleep Apnea (OSA)?Which medications in the drug class Dopamine/Norepinephrine Reuptake Inhibitors are used in the treatment of Obstructive Sleep Apnea (OSA)?

Author

Himanshu Wickramasinghe, MD, MBBS, Attending Physician, Pulmonary, Critical Care, and Sleep Medicine, Henry Mayo Newhall Memorial Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

James A Rowley, MD, Professor, Fellowship Program Director, Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP, Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director, Pulmonary Medicine General Practice Unit (F2), Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP, Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Philip M Gold, MD, Professor of Medicine, Chief of Pulmonary and Critical Care Medicine, Medical Director of Respiratory Care, Loma Linda University Medical Center

Disclosure: Nothing to disclose.

Ralph Downey, III, PhD, Staff Sleep Specialist, Cleveland Clinic Foundation; Associate Clinical Professor of Medicine, Loma Linda University School of Medicine

Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba Faculty of Medicine; Site Director, Respiratory Medicine, St Boniface General Hospital, Canada

Disclosure: Nothing to disclose.

References

  1. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med. 1976. 27:465-84. [View Abstract]
  2. Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The AASM Manual for the Scoring of Sleep and Associated Events. Westchester, IL: American Academy of Sleep Medicine; 2007.
  3. Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep. 1997 Sep. 20(9):705-6. [View Abstract]
  4. American Academy of Sleep Medicine. International Classification of Sleep Disorders. Diagnostic and Coding Manual. Second Edition. Westchester, Ill: American Academy of Sleep Medicine; 2005.
  5. Downey R 3rd, Perkin RM, MacQuarrie J. Upper airway resistance syndrome: sick, symptomatic but underrecognized. Sleep. 1993 Oct. 16(7):620-3. [View Abstract]
  6. Lugaresi E, Mondini S, Zucconi M, Montagna P, Cirignotta F. Staging of heavy snorers' disease. A proposal. Bull Eur Physiopathol Respir. 1983 Nov-Dec. 19(6):590-4. [View Abstract]
  7. Hoffstein V. Snoring. Chest. 1996 Jan. 109(1):201-22. [View Abstract]
  8. Bonnet MH. Effect of sleep disruption on sleep, performance, and mood. Sleep. 1985. 8(1):11-9. [View Abstract]
  9. Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest. 2007 Jul. 132(1):325-37. [View Abstract]
  10. Schwab RJ, Pasirstein M, Pierson R, Mackley A, Hachadoorian R, Arens R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med. 2003 Sep 1. 168(5):522-30. [View Abstract]
  11. White DP. Sleep apnea. Proc Am Thorac Soc. 2006. 3(1):124-8. [View Abstract]
  12. White DP. The pathogenesis of obstructive sleep apnea: advances in the past 100 years. Am J Respir Cell Mol Biol. 2006 Jan. 34(1):1-6. [View Abstract]
  13. McGinley BM, Schwartz AR, Schneider H, Kirkness JP, Smith PL, Patil SP. Upper airway neuromuscular compensation during sleep is defective in obstructive sleep apnea. J Appl Physiol. 2008 Jul. 105(1):197-205. [View Abstract]
  14. Patil SP, Schneider H, Marx JJ, Gladmon E, Schwartz AR, Smith PL. Neuromechanical control of upper airway patency during sleep. J Appl Physiol. 2007 Feb. 102(2):547-56. [View Abstract]
  15. Xie A, Skatrud JB, Puleo DS, Rahko PS, Dempsey JA. Apnea-hypopnea threshold for CO2 in patients with congestive heart failure. Am J Respir Crit Care Med. 2002 May 1. 165(9):1245-50. [View Abstract]
  16. Leung RS, Bradley TD. Sleep apnea and cardiovascular disease. Am J Respir Crit Care Med. 2001 Dec 15. 164(12):2147-65. [View Abstract]
  17. Xie A, Rutherford R, Rankin F, Wong B, Bradley TD. Hypocapnia and increased ventilatory responsiveness in patients with idiopathic central sleep apnea. Am J Respir Crit Care Med. 1995 Dec. 152(6 Pt 1):1950-5. [View Abstract]
  18. Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol. 1995 May. 78(5):1806-15. [View Abstract]
  19. Onal E, Burrows DL, Hart RH, Lopata M. Induction of periodic breathing during sleep causes upper airway obstruction in humans. J Appl Physiol. 1986 Oct. 61(4):1438-43. [View Abstract]
  20. Hudgel DW, Chapman KR, Faulks C, Hendricks C. Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep. Am Rev Respir Dis. 1987 Apr. 135(4):899-906. [View Abstract]
  21. Warner G, Skatrud JB, Dempsey JA. Effect of hypoxia-induced periodic breathing on upper airway obstruction during sleep. J Appl Physiol. 1987 Jun. 62(6):2201-11. [View Abstract]
  22. Badr MS, Kawak A, Skatrud JB, Morrell MJ, Zahn BR, Babcock MA. Effect of induced hypocapnic hypopnea on upper airway patency in humans during NREM sleep. Respir Physiol. 1997 Oct. 110(1):33-45. [View Abstract]
  23. Zhou XS, Shahabuddin S, Zahn BR, Babcock MA, Badr MS. Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep. J Appl Physiol. 2000 Jul. 89(1):192-9. [View Abstract]
  24. Sands SA, Edwards BA, Kelly VJ, Skuza EM, Davidson MR, Wilkinson MH, et al. Mechanism underlying accelerated arterial oxygen desaturation during recurrent apnea. Am J Respir Crit Care Med. 2010 Oct 1. 182(7):961-9. [View Abstract]
  25. Gozal D, Kheirandish-Gozal L. Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. Am J Respir Crit Care Med. 2008 Feb 15. 177(4):369-75. [View Abstract]
  26. Larkin EK, Patel SR, Goodloe RJ, Li Y, Zhu X, Gray-McGuire C, et al. A candidate gene study of obstructive sleep apnea in European Americans and African Americans. Am J Respir Crit Care Med. 2010 Oct 1. 182(7):947-53. [View Abstract]
  27. Cakirer B, Hans MG, Graham G, Aylor J, Tishler PV, Redline S. The relationship between craniofacial morphology and obstructive sleep apnea in whites and in African-Americans. Am J Respir Crit Care Med. 2001 Mar. 163(4):947-50. [View Abstract]
  28. Davies RJ, Ali NJ, Stradling JR. Neck circumference and other clinical features in the diagnosis of the obstructive sleep apnoea syndrome. Thorax. 1992 Feb. 47(2):101-5. [View Abstract]
  29. Rowley JA, Aboussouan LS, Badr MS. The use of clinical prediction formulas in the evaluation of obstructive sleep apnea. Sleep. 2000 Nov 1. 23(7):929-38. [View Abstract]
  30. Redline S, Tishler PV, Tosteson TD, Williamson J, Kump K, Browner I, et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med. 1995 Mar. 151(3 Pt 1):682-7. [View Abstract]
  31. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29. 328(17):1230-5. [View Abstract]
  32. Centers for Medicare and Medicaid Services. Decision Memo for Continuous Positive Airway Pressure (CPAP) Therapy for Obstructive Sleep Apnea (OSA) (CAG-00093R2).
  33. Goetting, C , Downey III R. Sick, symptomatic and undiagnosed. 2010.
  34. Johnson EO, Roth T. An epidemiologic study of sleep-disordered breathing symptoms among adolescents. Sleep. 2006 Sep 1. 29(9):1135-42. [View Abstract]
  35. Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med. 1998 Jan. 157(1):144-8. [View Abstract]
  36. Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, et al. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med. 2002 Apr 22. 162(8):893-900. [View Abstract]
  37. Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O. Sleep-disordered breathing in community-dwelling elderly. Sleep. 1991 Dec. 14(6):486-95. [View Abstract]
  38. Redline S, Kump K, Tishler PV, Browner I, Ferrette V. Gender differences in sleep disordered breathing in a community-based sample. Am J Respir Crit Care Med. 1994 Mar. 149(3 Pt 1):722-6. [View Abstract]
  39. Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB, Dempsey J. Sleep apnea and hypertension. A population-based study. Ann Intern Med. 1994 Mar 1. 120(5):382-8. [View Abstract]
  40. Shahar E, Redline S, Young T, Boland LL, Baldwin CM, Nieto FJ, et al. Hormone replacement therapy and sleep-disordered breathing. Am J Respir Crit Care Med. 2003 May 1. 167(9):1186-92. [View Abstract]
  41. Young T, Finn L, Austin D, Peterson A. Menopausal status and sleep-disordered breathing in the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med. 2003 May 1. 167(9):1181-5. [View Abstract]
  42. Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA. 2004 Apr 28. 291(16):2013-6. [View Abstract]
  43. O'Connor C, Thornley KS, Hanly PJ. Gender differences in the polysomnographic features of obstructive sleep apnea. Am J Respir Crit Care Med. 2000 May. 161(5):1465-72. [View Abstract]
  44. Ware JC, McBrayer RH, Scott JA. Influence of sex and age on duration and frequency of sleep apnea events. Sleep. 2000 Mar 15. 23(2):165-70. [View Abstract]
  45. Dancey DR, Hanly PJ, Soong C, Lee B, Shepard J Jr, Hoffstein V. Gender differences in sleep apnea: the role of neck circumference. Chest. 2003 May. 123(5):1544-50. [View Abstract]
  46. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005 Mar 19-25. 365(9464):1046-53. [View Abstract]
  47. Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008 Aug 1. 31(8):1071-8. [View Abstract]
  48. Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. Sleep. 2008 Aug 1. 31(8):1079-85. [View Abstract]
  49. Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O'Connor GT, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med. 2009 Aug. 6(8):e1000132. [View Abstract]
  50. Rich J, Raviv A, Raviv N, Brietzke SE. All-Cause Mortality and Obstructive Sleep Apnea Severity Revisited. Otolaryngol Head Neck Surg. 2012 Jun 11. [View Abstract]
  51. Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study. Ann Intern Med. 2012 Jan 17. 156(2):115-22. [View Abstract]
  52. Martinez-Garcia MA, Campos-Rodriguez F, Catalan-Serra P, Soler-Cataluna JJ, Almeida-Gonzalez C, De la Cruz Moron I, et al. Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long-term continuous positive airway pressure treatment: a prospective observational study. Am J Respir Crit Care Med. 2012 Nov 1. 186(9):909-16. [View Abstract]
  53. Campos-Rodriguez F, Pena-Grinan N, Reyes-Nunez N, De la Cruz-Moron I, Perez-Ronchel J, De la Vega-Gallardo F, et al. Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure. Chest. 2005 Aug. 128(2):624-33. [View Abstract]
  54. Martinez-Garcia MA, Soler-Cataluna JJ, Ejarque-Martinez L, Soriano Y, Roman-Sanchez P, Illa FB, et al. Continuous positive airway pressure treatment reduces mortality in patients with ischemic stroke and obstructive sleep apnea: a 5-year follow-up study. Am J Respir Crit Care Med. 2009 Jul 1. 180(1):36-41. [View Abstract]
  55. Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005 Mar 24. 352(12):1206-14. [View Abstract]
  56. Chaouat A, Weitzenblum E, Krieger J, Oswald M, Kessler R. Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients. Chest. 1996 Feb. 109(2):380-6. [View Abstract]
  57. Baguet JP, Barone-Rochette G, Levy P, Vautrin E, Pierre H, Ormezzano O, et al. Left ventricular diastolic dysfunction is linked to severity of obstructive sleep apnoea. Eur Respir J. 2010 Dec. 36(6):1323-9. [View Abstract]
  58. Sassani A, Findley LJ, Kryger M, Goldlust E, George C, Davidson TM. Reducing motor-vehicle collisions, costs, and fatalities by treating obstructive sleep apnea syndrome. Sleep. 2004 May 1. 27(3):453-8. [View Abstract]
  59. Horstmann S, Hess CW, Bassetti C, Gugger M, Mathis J. Sleepiness-related accidents in sleep apnea patients. Sleep. 2000 May 1. 23(3):383-9. [View Abstract]
  60. George CF, Smiley A. Sleep apnea & automobile crashes. Sleep. 1999 Sep 15. 22(6):790-5. [View Abstract]
  61. Barbe, Pericas J, Munoz A, Findley L, Anto JM, Agustí AG. Automobile accidents in patients with sleep apnea syndrome. An epidemiological and mechanistic study. Am J Respir Crit Care Med. 1998 Jul. 158(1):18-22. [View Abstract]
  62. Ghosh D, Jamson SL, Baxter PD, Elliott MW. Continuous measures of driving performance on an advanced office-based driving simulator can be used to predict simulator task failure in patients with obstructive sleep apnoea syndrome. Thorax. 2012 May 5. [View Abstract]
  63. Howard ME, Desai AV, Grunstein RR, Hukins C, Armstrong JG, Joffe D, et al. Sleepiness, sleep-disordered breathing, and accident risk factors in commercial vehicle drivers. Am J Respir Crit Care Med. 2004 Nov 1. 170(9):1014-21. [View Abstract]
  64. Powell NB, Schechtman KB, Riley RW, Guilleminault C, Chiang RP, Weaver EM. Sleepy driver near-misses may predict accident risks. Sleep. 2007 Mar 1. 30(3):331-42. [View Abstract]
  65. Risser MR, Ware JC, Freeman FG. Driving simulation with EEG monitoring in normal and obstructive sleep apnea patients. Sleep. 2000 May 1. 23(3):393-8. [View Abstract]
  66. George CF, Boudreau AC, Smiley A. Comparison of simulated driving performance in narcolepsy and sleep apnea patients. Sleep. 1996 Nov. 19(9):711-7. [View Abstract]
  67. Philip P, Sagaspe P, Taillard J, Valtat C, Moore N, Akerstedt T, et al. Fatigue, sleepiness, and performance in simulated versus real driving conditions. Sleep. 2005 Dec 1. 28(12):1511-6. [View Abstract]
  68. Turkington PM, Sircar M, Allgar V, Elliott MW. Relationship between obstructive sleep apnoea, driving simulator performance, and risk of road traffic accidents. Thorax. 2001 Oct. 56(10):800-5. [View Abstract]
  69. Hack M, Davies RJ, Mullins R, Choi SJ, Ramdassingh-Dow S, Jenkinson C, et al. Randomised prospective parallel trial of therapeutic versus subtherapeutic nasal continuous positive airway pressure on simulated steering performance in patients with obstructive sleep apnoea. Thorax. 2000 Mar. 55(3):224-31. [View Abstract]
  70. Turkington PM, Sircar M, Saralaya D, Elliott MW. Time course of changes in driving simulator performance with and without treatment in patients with sleep apnoea hypopnoea syndrome. Thorax. 2004 Jan. 59(1):56-9. [View Abstract]
  71. George CF. Reduction in motor vehicle collisions following treatment of sleep apnoea with nasal CPAP. Thorax. 2001 Jul. 56(7):508-12. [View Abstract]
  72. Findley L, Smith C, Hooper J, Dineen M, Suratt PM. Treatment with nasal CPAP decreases automobile accidents in patients with sleep apnea. Am J Respir Crit Care Med. 2000 Mar. 161(3 Pt 1):857-9. [View Abstract]
  73. Pack AI, Pien GW. How much do crashes related to obstructive sleep apnea cost?. Sleep. 2004 May 1. 27(3):369-70. [View Abstract]
  74. American Thoracic Society. Sleep apnea, sleepiness, and driving risk. American Thoracic Society. Am J Respir Crit Care Med. 1994 Nov. 150(5 Pt 1):1463-73. [View Abstract]
  75. Punjabi NM, Bandeen-Roche K, Young T. Predictors of objective sleep tendency in the general population. Sleep. 2003 Sep. 26(6):678-83. [View Abstract]
  76. Benbadis SR, Mascha E, Perry MC, Wolgamuth BR, Smolley LA, Dinner DS. Association between the Epworth sleepiness scale and the multiple sleep latency test in a clinical population. Ann Intern Med. 1999 Feb 16. 130(4 Pt 1):289-92. [View Abstract]
  77. Chervin RD, Aldrich MS. The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea. Neurology. 1999 Jan 1. 52(1):125-31. [View Abstract]
  78. Punjabi NM, O'hearn DJ, Neubauer DN, Nieto FJ, Schwartz AR, Smith PL, et al. Modeling hypersomnolence in sleep-disordered breathing. A novel approach using survival analysis. Am J Respir Crit Care Med. 1999 Jun. 159(6):1703-9. [View Abstract]
  79. Black JE, Hirshkowitz M. Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome. Sleep. 2005 Apr 1. 28(4):464-71. [View Abstract]
  80. Chervin RD. Sleepiness, fatigue, tiredness, and lack of energy in obstructive sleep apnea. Chest. 2000 Aug. 118(2):372-9. [View Abstract]
  81. Castronovo V, Canessa N, Strambi LF, Aloia MS, Consonni M, Marelli S, et al. Brain activation changes before and after PAP treatment in obstructive sleep apnea. Sleep. 2009 Sep 1. 32(9):1161-72. [View Abstract]
  82. Freedman DS, Khan LK, Serdula MK, Galuska DA, Dietz WH. Trends and correlates of class 3 obesity in the United States from 1990 through 2000. JAMA. 2002 Oct 9. 288(14):1758-61. [View Abstract]
  83. Nuckton TJ, Glidden DV, Browner WS, Claman DM. Physical examination: Mallampati score as an independent predictor of obstructive sleep apnea. Sleep. 2006 Jul 1. 29(7):903-8. [View Abstract]
  84. Chung F, Yegneswaran B, Liao P, Chung SA, Vairavanathan S, Islam S, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008 May. 108(5):812-21. [View Abstract]
  85. Chung F, Subramanyam R, Liao P, Sasaki E, Shapiro C, Sun Y. High STOP-Bang score indicates a high probability of obstructive sleep apnoea. Br J Anaesth. 2012 May. 108(5):768-75. [View Abstract]
  86. Ramachandran SK, Kheterpal S, Consens F, Shanks A, Doherty TM, Morris M, et al. Derivation and validation of a simple perioperative sleep apnea prediction score. Anesth Analg. 2010 Apr 1. 110(4):1007-15. [View Abstract]
  87. Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, et al. Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation. 2008 Sep 2. 118(10):1080-111. [View Abstract]
  88. Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000 Apr 12. 283(14):1829-36. [View Abstract]
  89. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 May 11. 342(19):1378-84. [View Abstract]
  90. O'Connor GT, Caffo B, Newman AB, Quan SF, Rapoport DM, Redline S, et al. Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2009 Jun 15. 179(12):1159-64. [View Abstract]
  91. Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, et al. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation. 2003 Jan 7. 107(1):68-73. [View Abstract]
  92. Faccenda JF, Mackay TW, Boon NA, Douglas NJ. Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med. 2001 Feb. 163(2):344-8. [View Abstract]
  93. Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet. 2002 Jan 19. 359(9302):204-10. [View Abstract]
  94. Barbe F, Durán-Cantolla J, Capote F, de la Pena M, Chiner E, Masa JF, et al. Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010 Apr 1. 181(7):718-26. [View Abstract]
  95. Pepin JL, Tamisier R, Barone-Rochette G, Launois SH, Levy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010 Oct 1. 182(7):954-60. [View Abstract]
  96. Drager LF, Bortolotto LA, Lorenzi MC, Figueiredo AC, Krieger EM, Lorenzi-Filho G. Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2005 Sep 1. 172(5):613-8. [View Abstract]
  97. Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2007 Oct 1. 176(7):706-12. [View Abstract]
  98. Wang H, Parker JD, Newton GE, Floras JS, Mak S, Chiu KL, et al. Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol. 2007 Apr 17. 49(15):1625-31. [View Abstract]
  99. Kaneko Y, Floras JS, Usui K, Plante J, Tkacova R, Kubo T, et al. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. N Engl J Med. 2003 Mar 27. 348(13):1233-41. [View Abstract]
  100. Javaheri S, Caref EB, Chen E, Tong KB, Abraham WT. Sleep apnea testing and outcomes in a large cohort of medicare beneficiaries with newly diagnosed heart failure. Am J Respir Crit Care Med. 2011 Feb 15. 183(4):539-46. [View Abstract]
  101. Montemurro LT, Floras JS, Millar PJ, Kasai T, Gabriel JM, Spaak J, et al. Inverse Relationship of Subjective Daytime Sleepiness to Sympathetic Activity in Heart Failure Patients with Obstructive Sleep Apnea. Chest. 2012 Apr 26. [View Abstract]
  102. Mehra R, Stone KL, Varosy PD, Hoffman AR, Marcus GM, Blackwell T, et al. Nocturnal Arrhythmias across a spectrum of obstructive and central sleep-disordered breathing in older men: outcomes of sleep disorders in older men (MrOS sleep) study. Arch Intern Med. 2009 Jun 22. 169(12):1147-55. [View Abstract]
  103. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001 Jan. 163(1):19-25. [View Abstract]
  104. Arzt M, Young T, Finn L, Skatrud JB, Bradley TD. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med. 2005 Dec 1. 172(11):1447-51. [View Abstract]
  105. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005 Nov 10. 353(19):2034-41. [View Abstract]
  106. Munoz R, Duran-Cantolla J, Martinez-Vila E, Gallego J, Rubio R, Aizpuru F, et al. Severe sleep apnea and risk of ischemic stroke in the elderly. Stroke. 2006 Sep. 37(9):2317-21. [View Abstract]
  107. Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med. 2002 Mar 1. 165(5):670-6. [View Abstract]
  108. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL. Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med. 2002 Mar 1. 165(5):677-82. [View Abstract]
  109. Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol. 2004 Sep 15. 160(6):521-30. [View Abstract]
  110. Reichmuth KJ, Austin D, Skatrud JB, Young T. Association of sleep apnea and type II diabetes: a population-based study. Am J Respir Crit Care Med. 2005 Dec 15. 172(12):1590-5. [View Abstract]
  111. Dyugovskaya L, Lavie P, Lavie L. Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med. 2002 Apr 1. 165(7):934-9. [View Abstract]
  112. Lavie L, Vishnevsky A, Lavie P. Evidence for lipid peroxidation in obstructive sleep apnea. Sleep. 2004 Feb 1. 27(1):123-8. [View Abstract]
  113. Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation. 2003 Mar 4. 107(8):1129-34. [View Abstract]
  114. Larkin EK, Rosen CL, Kirchner HL, Storfer-Isser A, Emancipator JL, Johnson NL, et al. Variation of C-reactive protein levels in adolescents: association with sleep-disordered breathing and sleep duration. Circulation. 2005 Apr 19. 111(15):1978-84. [View Abstract]
  115. Minoguchi K, Yokoe T, Tazaki T, Minoguchi H, Tanaka A, Oda N, et al. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med. 2005 Sep 1. 172(5):625-30. [View Abstract]
  116. Tazaki T, Minoguchi K, Yokoe T, Samson KT, Minoguchi H, Tanaka A, et al. Increased levels and activity of matrix metalloproteinase-9 in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2004 Dec 15. 170(12):1354-9. [View Abstract]
  117. Taheri S, Austin D, Lin L, Nieto FJ, Young T, Mignot E. Correlates of serum C-reactive protein (CRP)--no association with sleep duration or sleep disordered breathing. Sleep. 2007 Aug 1. 30(8):991-6. [View Abstract]
  118. Patt BT, Jarjoura D, Haddad DN, Sen CK, Roy S, Flavahan NA, et al. Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2010 Dec 15. 182(12):1540-5. [View Abstract]
  119. Ip MS, Lam B, Chan LY, Zheng L, Tsang KW, Fung PC, et al. Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure. Am J Respir Crit Care Med. 2000 Dec. 162(6):2166-71. [View Abstract]
  120. Ip MS, Tse HF, Lam B, Tsang KW, Lam WK. Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med. 2004 Feb 1. 169(3):348-53. [View Abstract]
  121. Imadojemu VA, Gleeson K, Quraishi SA, Kunselman AR, Sinoway LI, Leuenberger UA. Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy. Am J Respir Crit Care Med. 2002 Apr 1. 165(7):950-3. [View Abstract]
  122. Nieto FJ, Herrington DM, Redline S, Benjamin EJ, Robbins JA. Sleep apnea and markers of vascular endothelial function in a large community sample of older adults. Am J Respir Crit Care Med. 2004 Feb 1. 169(3):354-60. [View Abstract]
  123. Aronsohn RS, Whitmore H, Van Cauter E, Tasali E. Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes. Am J Respir Crit Care Med. 2010 Mar 1. 181(5):507-13. [View Abstract]
  124. Pelletier-Fleury N, Rakotonanahary D, Fleury B. The age and other factors in the evaluation of compliance with nasal continuous positive airway pressure for obstructive sleep apnea syndrome. A Cox's proportional hazard analysis. Sleep Med. 2001 May. 2(3):225-232. [View Abstract]
  125. Parish JM, Lyng PJ, Wisbey J. Compliance with CPAP in elderly patients with OSA. Sleep Med. 2000 Jul 1. 1(3):209-214. [View Abstract]
  126. Gozal D, Pope DW Jr. Snoring during early childhood and academic performance at ages thirteen to fourteen years. Pediatrics. 2001 Jun. 107(6):1394-9. [View Abstract]
  127. Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics. 1998 Sep. 102(3 Pt 1):616-20. [View Abstract]
  128. Chervin RD, Clarke DF, Huffman JL, Szymanski E, Ruzicka DL, Miller V, et al. School performance, race, and other correlates of sleep-disordered breathing in children. Sleep Med. 2003 Jan. 4(1):21-7. [View Abstract]
  129. Friedman BC, Hendeles-Amitai A, Kozminsky E, Leiberman A, Friger M, Tarasiuk A, et al. Adenotonsillectomy improves neurocognitive function in children with obstructive sleep apnea syndrome. Sleep. 2003 Dec 15. 26(8):999-1005. [View Abstract]
  130. Chervin RD, Archbold KH. Hyperactivity and polysomnographic findings in children evaluated for sleep-disordered breathing. Sleep. 2001 May 1. 24(3):313-20. [View Abstract]
  131. Chervin RD, Archbold KH, Dillon JE, Panahi P, Pituch KJ, Dahl RE, et al. Inattention, hyperactivity, and symptoms of sleep-disordered breathing. Pediatrics. 2002 Mar. 109(3):449-56. [View Abstract]
  132. Keller DM. Childhood asthma raises risk for adult sleep apnea. Medscape Medical News. June 6, 2013.
  133. Franklin KA, Holmgren PA, Jonsson F, Poromaa N, Stenlund H, Svanborg E. Snoring, pregnancy-induced hypertension, and growth retardation of the fetus. Chest. 2000 Jan. 117(1):137-41. [View Abstract]
  134. Hartenbaum N, Collop N, Rosen IM, Phillips B, George CF, Rowley JA, et al. Sleep apnea and commercial motor vehicle operators: statement from the joint Task Force of the American College of Chest Physicians, American College of Occupational and Environmental Medicine, and the National Sleep Foundation. J Occup Environ Med. 2006 Sep. 48(9 Suppl):S4-37. [View Abstract]
  135. Hartenbaum N, Collop N, Rosen IM, Phillips B, George CF, Rowley JA, et al. Sleep apnea and commercial motor vehicle operators: Statement from the joint task force of the American College of Chest Physicians, the American College of Occupational and Environmental Medicine, and the National Sleep Foundation. Chest. 2006 Sep. 130(3):902-5. [View Abstract]
  136. Miller CM, Khanna A, Strohl KP. Assessment and policy for commercial driver license referrals. J Clin Sleep Med. 2007 Jun 15. 3(4):417-23. [View Abstract]
  137. Sansa G, Iranzo A, Santamaria J. Obstructive sleep apnea in narcolepsy. Sleep Med. 2010 Jan. 11(1):93-5. [View Abstract]
  138. Anderson P. New Guideline for Sleep Apnea Diagnosis. Medscape Medical News. Available at http://www.medscape.com/viewarticle/829717#1. Accessed: August 13, 2014.
  139. [Guideline] Qaseem A, Dallas P, Owens DK, et al. Diagnosis of Obstructive Sleep Apnea in Adults: A Clinical Practice Guideline From the American College of Physicians. Annals of Internal Medicine. Available at http://annals.org/article.aspx?articleid=1892620. Accessed: August 13, 2014.
  140. Cintra F, Tufik S, D'Almeida V, Calegare BF, de Paola A, Oliveira W, et al. Cysteine: a potential biomarker for obstructive sleep apnea. Chest. 2011 Feb. 139(2):246-52. [View Abstract]
  141. Flemons WW, Littner MR, Rowley JA, Gay P, Anderson WM, Hudgel DW, et al. Home diagnosis of sleep apnea: a systematic review of the literature. An evidence review cosponsored by the American Academy of Sleep Medicine, the American College of Chest Physicians, and the American Thoracic Society. Chest. 2003 Oct. 124(4):1543-79. [View Abstract]
  142. Ahmed M, Patel NP, Rosen I. Portable monitors in the diagnosis of obstructive sleep apnea. Chest. 2007 Nov. 132(5):1672-7. [View Abstract]
  143. Mulgrew AT, Fox N, Ayas NT, Ryan CF. Diagnosis and initial management of obstructive sleep apnea without polysomnography: a randomized validation study. Ann Intern Med. 2007 Feb 6. 146(3):157-66. [View Abstract]
  144. Berry RB, Hill G, Thompson L, McLaurin V. Portable monitoring and autotitration versus polysomnography for the diagnosis and treatment of sleep apnea. Sleep. 2008 Oct 1. 31(10):1423-31. [View Abstract]
  145. Kuna ST, Gurubhagavatula I, Maislin G, et al. Noninferiority of functional outcome in ambulatory management of obstructive sleep apnea. Am J Respir Crit Care Med. 2011 May 1. 183(9):1238-44. [View Abstract]
  146. Chai-Coetzer CL, Antic NA, Rowland LS, Catcheside PG, Esterman A, Reed RL, et al. A simplified model of screening questionnaire and home monitoring for obstructive sleep apnoea in primary care. Thorax. 2011 Mar. 66(3):213-9. [View Abstract]
  147. Chai-Coetzer CL, Antic NA, Hamilton GS, McArdle N, Wong K, Yee BJ, et al. Physician Decision Making and Clinical Outcomes With Laboratory Polysomnography or Limited-Channel Sleep Studies for Obstructive Sleep Apnea: A Randomized Trial. Ann Intern Med. 2017 Jan 24. [View Abstract]
  148. Parry NM. Home Sleep Testing as Good as Laboratory Testing for Apnea. Medscape Medical News. Available at http://www.medscape.com/viewarticle/874828?src=soc_tw_170125_mscpedt_news_pulm_sleepapnea#vp_1. January 23, 2017; Accessed: January 27, 2017.
  149. Collop NA, Anderson WM, Boehlecke B, Claman D, Goldberg R, Gottlieb DJ, et al. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2007 Dec 15. 3(7):737-47. [View Abstract]
  150. Brooks M. Disposable Skin Patch Detects Sleep Apnea at Home. Medscape News & Perspective. Available at https://www.medscape.com/viewarticle/881212. June 6, 2017; Accessed: January 10, 2018.
  151. SLEEP 2017. 31st Annual Meeting of the Associated Professional Sleep Societies. Presented June 5, 2017. Abstract 0448:
  152. Bonnet MH, Arand DL. Impact of motivation on Multiple Sleep Latency Test and Maintenance of Wakefulness Test measurements. J Clin Sleep Med. 2005 Oct 15. 1(4):386-90. [View Abstract]
  153. Morgenthaler TI, Kapen S, Lee-Chiong T, Alessi C, Boehlecke B, Brown T, et al. Practice parameters for the medical therapy of obstructive sleep apnea. Sleep. 2006 Aug 1. 29(8):1031-5. [View Abstract]
  154. [Guideline] Qaseem A, Holty JE, Owens DK, et al. Management of Obstructive Sleep Apnea in Adults: A Clinical Practice Guideline From the American College of Physicians. Annals of Internal Medicine. Available at http://annals.org/article.aspx?articleid=1742606. Accessed: August 13, 2014.
  155. Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, et al. Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J Clin Sleep Med. 2008 Apr 15. 4(2):157-71. [View Abstract]
  156. Kushida CA, Littner MR, Hirshkowitz M, Morgenthaler TI, Alessi CA, Bailey D, et al. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep. 2006 Mar 1. 29(3):375-80. [View Abstract]
  157. Gay P, Weaver T, Loube D, Iber C. Evaluation of positive airway pressure treatment for sleep related breathing disorders in adults. Sleep. 2006 Mar 1. 29(3):381-401. [View Abstract]
  158. Smith I, Lasserson TJ. Pressure modification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2009 Oct 7. CD003531. [View Abstract]
  159. Vennelle M, White S, Riha RL, Mackay TW, Engleman HM, Douglas NJ. Randomized controlled trial of variable-pressure versus fixed-pressure continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). Sleep. 2010 Feb 1. 33(2):267-71. [View Abstract]
  160. Morgenthaler TI, Aurora RN, Brown T, Zak R, Alessi C, Boehlecke B, et al. Practice parameters for the use of autotitrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome: an update for 2007. An American Academy of Sleep Medicine report. Sleep. 2008 Jan 1. 31(1):141-7. [View Abstract]
  161. Engleman HM, Martin SE, Deary IJ, Douglas NJ. Effect of continuous positive airway pressure treatment on daytime function in sleep apnoea/hypopnoea syndrome. Lancet. 1994 Mar 5. 343(8897):572-5. [View Abstract]
  162. Engleman HM, Kingshott RN, Wraith PK, Mackay TW, Deary IJ, Douglas NJ. Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep Apnea/Hypopnea syndrome. Am J Respir Crit Care Med. 1999 Feb. 159(2):461-7. [View Abstract]
  163. Sharma SK, Agrawal S, Damodaran D, Sreenivas V, Kadhiravan T, Lakshmy R, et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med. 2011 Dec 15. 365(24):2277-86. [View Abstract]
  164. Bennett LS, Barbour C, Langford B, Stradling JR, Davies RJ. Health status in obstructive sleep apnea: relationship with sleep fragmentation and daytine sleepiness, and effects of continuous positive airway pressure treatment. Am J Respir Crit Care Med. 1999 Jun. 159(6):1884-90. [View Abstract]
  165. Bahammam A, Delaive K, Ronald J, Manfreda J, Roos L, Kryger MH. Health care utilization in males with obstructive sleep apnea syndrome two years after diagnosis and treatment. Sleep. 1999 Sep 15. 22(6):740-7. [View Abstract]
  166. Kohler M, Stoewhas AC, Ayers L, et al. Effects of Continuous Positive Airway Pressure Therapy Withdrawal in Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial. Am. J. Respir. Crit. Care Med. November 2011. 184:
  167. Crawford MR, Bartlett DJ, Coughlin SR, Phillips CL, Neill AM, Espie CA, et al. The effect of continuous positive airway pressure usage on sleepiness in obstructive sleep apnoea: real effects or expectation of benefit?. Thorax. 2012 May 26. [View Abstract]
  168. Lin HS, Zuliani G, Amjad EH, Prasad AS, Badr MS, Pan CJ, et al. Treatment compliance in patients lost to follow-up after polysomnography. Otolaryngol Head Neck Surg. 2007 Feb. 136(2):236-40. [View Abstract]
  169. Weaver TE, Maislin G, Dinges DF, Bloxham T, George CF, Greenberg H, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007 Jun 1. 30(6):711-9. [View Abstract]
  170. Popescu G, Latham M, Allgar V, Elliott MW. Continuous positive airway pressure for sleep apnoea/hypopnoea syndrome: usefulness of a 2 week trial to identify factors associated with long term use. Thorax. 2001 Sep. 56(9):727-33. [View Abstract]
  171. Aloia MS, Arnedt JT, Stanchina M, Millman RP. How early in treatment is PAP adherence established? Revisiting night-to-night variability. Behav Sleep Med. 2007. 5(3):229-40. [View Abstract]
  172. Aloia MS, Arnedt JT, Stepnowsky C, Hecht J, Borrelli B. Predicting treatment adherence in obstructive sleep apnea using principles of behavior change. J Clin Sleep Med. 2005 Oct 15. 1(4):346-53. [View Abstract]
  173. McArdle N, Devereux G, Heidarnejad H, Engleman HM, Mackay TW, Douglas NJ. Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 1999 Apr. 159(4 Pt 1):1108-14. [View Abstract]
  174. Platt AB, Kuna ST, Field SH, Chen Z, Gupta R, Roche DF, et al. Adherence to sleep apnea therapy and use of lipid-lowering drugs: a study of the healthy-user effect. Chest. 2010 Jan. 137(1):102-8. [View Abstract]
  175. Bakker JP, Marshall NS. Flexible pressure delivery modification of continuous positive airway pressure for obstructive sleep apnea does not improve compliance with therapy: Systematic review and meta-analysis. Chest. 2010 Dec 30. [View Abstract]
  176. Collen J, Holley A, Lettieri C, Shah A, Roop S. The impact of split-night versus traditional sleep studies on CPAP compliance. Sleep Breath. 2010 Jun. 14(2):93-9. [View Abstract]
  177. Chervin RD, Theut S, Bassetti C, Aldrich MS. Compliance with nasal CPAP can be improved by simple interventions. Sleep. 1997 Apr. 20(4):284-9. [View Abstract]
  178. Massie CA, Hart RW, Peralez K, Richards GN. Effects of humidification on nasal symptoms and compliance in sleep apnea patients using continuous positive airway pressure. Chest. 1999 Aug. 116(2):403-8. [View Abstract]
  179. Hoy CJ, Vennelle M, Kingshott RN, Engleman HM, Douglas NJ. Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome?. Am J Respir Crit Care Med. 1999 Apr. 159(4 Pt 1):1096-100. [View Abstract]
  180. Richards D, Bartlett DJ, Wong K, Malouff J, Grunstein RR. Increased adherence to CPAP with a group cognitive behavioral treatment intervention: a randomized trial. Sleep. 2007 May 1. 30(5):635-40. [View Abstract]
  181. Likar LL, Panciera TM, Erickson AD, Rounds S. Group education sessions and compliance with nasal CPAP therapy. Chest. 1997 May. 111(5):1273-7. [View Abstract]
  182. Smith I, Nadig V, Lasserson TJ. Educational, supportive and behavioural interventions to improve usage of continuous positive airway pressure machines for adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2009 Apr 15. CD007736. [View Abstract]
  183. Fuchs FS, Pittarelli A, Hahn EG, Ficker JH. Adherence to continuous positive airway pressure therapy for obstructive sleep apnea: impact of patient education after a longer treatment period. Respiration. 2010. 80(1):32-7. [View Abstract]
  184. Reeves-Hoche MK, Hudgel DW, Meck R, Witteman R, Ross A, Zwillich CW. Continuous versus bilevel positive airway pressure for obstructive sleep apnea. Am J Respir Crit Care Med. 1995 Feb. 151(2 Pt 1):443-9. [View Abstract]
  185. Gay PC, Herold DL, Olson EJ. A randomized, double-blind clinical trial comparing continuous positive airway pressure with a novel bilevel pressure system for treatment of obstructive sleep apnea syndrome. Sleep. 2003 Nov 1. 26(7):864-9. [View Abstract]
  186. Kushida CA, Morgenthaler TI, Littner MR, Alessi CA, Bailey D, Coleman J Jr, et al. Practice parameters for the treatment of snoring and Obstructive Sleep Apnea with oral appliances: an update for 2005. Sleep. 2006 Feb 1. 29(2):240-3. [View Abstract]
  187. Ferguson KA, Cartwright R, Rogers R, Schmidt-Nowara W. Oral appliances for snoring and obstructive sleep apnea: a review. Sleep. 2006 Feb 1. 29(2):244-62. [View Abstract]
  188. American Sleep Disorders Association. Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances. American Sleep Disorders Association. Sleep. 1995 Jul. 18(6):511-3. [View Abstract]
  189. Lazard DS, Blumen M, Levy P, Chauvin P, Fragny D, Buchet I, et al. The tongue-retaining device: efficacy and side effects in obstructive sleep apnea syndrome. J Clin Sleep Med. 2009 Oct 15. 5(5):431-8. [View Abstract]
  190. Engleman HM, McDonald JP, Graham D, Lello GE, Kingshott RN, Coleman EL, et al. Randomized crossover trial of two treatments for sleep apnea/hypopnea syndrome: continuous positive airway pressure and mandibular repositioning splint. Am J Respir Crit Care Med. 2002 Sep 15. 166(6):855-9. [View Abstract]
  191. Phillips CL, Grunstein RR, Darendeliler MA, Mihailidou AS, Srinivasan VK, Yee BJ, et al. Health Outcomes of Continuous Positive Airway Pressure versus Oral Appliance Treatment for Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2013 Apr 15. 187(8):879-87. [View Abstract]
  192. Tsai WH, Vazquez JC, Oshima T, Dort L, Roycroft B, Lowe AA, et al. Remotely controlled mandibular positioner predicts efficacy of oral appliances in sleep apnea. Am J Respir Crit Care Med. 2004 Aug 15. 170(4):366-70. [View Abstract]
  193. Raphaelson MA, Alpher EJ, Bakker KW, Perlstrom JR. Oral appliance therapy for obstructive sleep apnea syndrome: progressive mandibular advancement during polysomnography. Cranio. 1998 Jan. 16(1):44-50. [View Abstract]
  194. Petelle B, Vincent G, Gagnadoux F, Rakotonanahary D, Meyer B, Fleury B. One-night mandibular advancement titration for obstructive sleep apnea syndrome: a pilot study. Am J Respir Crit Care Med. 2002 Apr 15. 165(8):1150-3. [View Abstract]
  195. Phillips B. Upper airway surgery does not have a major role in the treatment of sleep apnea. J Clin Sleep Med. 2005. 1:241-5.
  196. Powell N. Upper airway surgery does have a major role in the treatment of obstructive sleep apnea "the tail end of the dog". Pro. J Clin Sleep Med. 2005 Jul 15. 1(3):236-40. [View Abstract]
  197. Sher AE. Upper airway surgery for obstructive sleep apnea. Sleep Med Rev. 2002 Jun. 6(3):195-212. [View Abstract]
  198. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep. 1996 Feb. 19(2):156-77. [View Abstract]
  199. Li KK, Powell NB, Riley RW, Troell R, Guilleminault C. Overview of phase I surgery for obstructive sleep apnea syndrome. Ear Nose Throat J. 1999 Nov. 78(11):836-7, 841-5. [View Abstract]
  200. Li KK, Riley RW, Powell NB, Troell R, Guilleminault C. Overview of phase II surgery for obstructive sleep apnea syndrome. Ear Nose Throat J. 1999 Nov. 78(11):851, 854-7. [View Abstract]
  201. Powell NB, Riley RW, Troell RJ, Li K, Blumen MB, Guilleminault C. Radiofrequency volumetric tissue reduction of the palate in subjects with sleep-disordered breathing. Chest. 1998 May. 113(5):1163-74. [View Abstract]
  202. Li KK, Powell NB, Riley RW, Troell RJ, Guilleminault C. Radiofrequency volumetric reduction of the palate: An extended follow-up study. Otolaryngol Head Neck Surg. 2000 Mar. 122(3):410-4. [View Abstract]
  203. Coleman SC, Smith TL. Midline radiofrequency tissue reduction of the palate for bothersome snoring and sleep-disordered breathing: A clinical trial. Otolaryngol Head Neck Surg. 2000 Mar. 122(3):387-94. [View Abstract]
  204. Grunstein RR, Stenlof K, Hedner JA, Peltonen M, Karason K, Sjostrom L. Two year reduction in sleep apnea symptoms and associated diabetes incidence after weight loss in severe obesity. Sleep. 2007 Jun 1. 30(6):703-10. [View Abstract]
  205. [Guideline] Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009 Jun 15. 5(3):263-76. [View Abstract]
  206. [Guideline] SAGES guideline for clinical application of laparoscopic bariatric surgery. Surg Obes Relat Dis. 2009 May-Jun. 5(3):387-405. [View Abstract]
  207. [Guideline] Schumann R, Jones SB, Cooper B, Kelley SD, Bosch MV, Ortiz VE, et al. Update on best practice recommendations for anesthetic perioperative care and pain management in weight loss surgery, 2004-2007. Obesity (Silver Spring). 2009 May. 17(5):889-94. [View Abstract]
  208. Woodson BT, Steward DL, Weaver EM, Javaheri S. A randomized trial of temperature-controlled radiofrequency, continuous positive airway pressure, and placebo for obstructive sleep apnea syndrome. Otolaryngol Head Neck Surg. 2003 Jun. 128(6):848-61. [View Abstract]
  209. Weaver EM, Maynard C, Yueh B. Survival of veterans with sleep apnea: continuous positive airway pressure versus surgery. Otolaryngol Head Neck Surg. 2004 Jun. 130(6):659-65. [View Abstract]
  210. Walker-Engstrom ML, Tegelberg A, Wilhelmsson B, Ringqvist I. 4-year follow-up of treatment with dental appliance or uvulopalatopharyngoplasty in patients with obstructive sleep apnea: a randomized study. Chest. 2002 Mar. 121(3):739-46. [View Abstract]
  211. Guilleminault C, Philip P. Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patient stays hypersomnolent despite treatment). Sleep. 1996 Nov. 19(9 Suppl):S117-22. [View Abstract]
  212. Roizenblatt S, Guilleminault C, Poyares D, Cintra F, Kauati A, Tufik S. A double-blind, placebo-controlled, crossover study of sildenafil in obstructive sleep apnea. Arch Intern Med. 2006 Sep 18. 166(16):1763-7. [View Abstract]
  213. Kingshott RN, Vennelle M, Coleman EL, Engleman HM, Mackay TW, Douglas NJ. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 2001 Mar. 163(4):918-23. [View Abstract]
  214. Pack AI, Black JE, Schwartz JR, Matheson JK. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med. 2001 Nov 1. 164(9):1675-81. [View Abstract]
  215. Schwartz JR, Hirshkowitz M, Erman MK, Schmidt-Nowara W. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea: a 12-week, open-label study. Chest. 2003 Dec. 124(6):2192-9. [View Abstract]
  216. Schweitzer PK, Rosenberg R, Zammit GK, Gotfried M, Chen D, Carter LP, et al. Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3): A Randomized Controlled Trial. Am J Respir Crit Care Med. 2018 Dec 6. [View Abstract]
  217. Kuna ST, Gurubhagavatula I, Maislin G, et al. Non-inferiority of Functional Outcome in Ambulatory Management of Obstructive Sleep Apnea. Resp & Crit Care Med. Jan 20, 2011.
  218. Veasey SC, Guilleminault C, Strohl KP, Sanders MH, Ballard RD, Magalang UJ. Medical therapy for obstructive sleep apnea: a review by the Medical Therapy for Obstructive Sleep Apnea Task Force of the Standards of Practice Committee of the American Academy of Sleep Medicine. Sleep. 2006 Aug 1. 29(8):1036-44. [View Abstract]

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occupies an intermediate position between these extremes. Note areas of overlap among the conditions.

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occupies an intermediate position between these extremes. Note areas of overlap among the conditions.

Tonsil grades.

The Mallampati Classification is illustrated. The airway class is based on this visual heuristic.

In this polysomnogram summary graph, obstructive sleep apnea (OSA) severity and the degree of oxygen desaturation (SpO2%) worsen in rapid eye movement (REM) sleep (the black underlined sections) compared with non-REM sleep. This is often the case in OSA patients, especially in OSA patients with comorbid lung disease.

Potential relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and the metabolic syndrome. OSAHS has been associated with 3 of the 5 major clinical abnormalities associated with the metabolic syndrome, which is hypertension, insulin resistance, and proinflammatory/oxidative stress. OSAHS may be contributing to and/or modulating the severity of these metabolic abnormalities.

MRI rendering of a patient without obstructive sleep apnea (OSA) (left panel) and a patient with OSA (right panel).

Obstructive sleep apnea. Note the absence of flow (red arrow) despite paradoxical respiratory effort (green arrow).

Central sleep apnea (thick areas). Note the absence of both flow and respiratory effort (green double arrows).

Comparison of a central apnea (box) and obstructive apnea (circle).

Mixed sleep apnea. Note that the apnea (orange arrow) begins as a central apnea (effort absent; red double arrow) and ends as an obstructive apnea (effort present; green double arrow). Note the arousal (blue arrow) that terminates the apnea and the desaturation (purple arrow) that follows.

A 2-minute recording of sleep showing 4 hypopneas (thick arrows) and associated oxygen desaturations (red arrows). This recording illustrates the recurrent nature of the sleep-disordered breathing observed in many patients.

Top image is 3-dimensional surface renderings of the upper airway demonstrating the effect of progressive increases in continuous positive airway pressure (CPAP) from 0-15 cm of water on upper-airway volume in a patient with upper airway narrowing. CPAP significantly increases airway volume in the retropalatal (RP) and retroglossal (RG) regions. Bottom image is soft tissue images in the same patient in the RP region at analogous levels of CPAP. With increasing CPAP, the upper airway progressively enlarges, particularly in the lateral dimension. Note the progressive thinning of the lateral pharyngeal walls as the level of CPAP increases. Little movement occurs in the parapharyngeal fat pads, the white structures lateral to the airway. The first image in each series depicts the baseline upper airway narrowing present in this patient.

Effect of nasal continuous positive airway pressure (CPAP) on oxygen saturation in sleep apnea. The upper portion of this figure shows the raw oxygen saturation trace from 1 night of a sleep study. Below the raw trace are vertical lines that indicate the presence of either an apnea or hypopnea. Before CPAP, frequent respiratory events with significant desaturations occurred. During the night, CPAP was applied, resulting in the elimination of the apnea and hypopneas and normalization of the oxygen trace.

Examples of good (upper panel) and poor (lower panel) compliance. In the upper panel, the patient is using continuous positive airway pressure (CPAP) most nights and generally for more than 4 hours (solid black line). In the lower panel, the patient is using CPAP infrequently and, when used, is wearing the CPAP device for less than 4 hours.

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occupies an intermediate position between these extremes. Note areas of overlap among the conditions.

Approach to a patient with excessive daytime sleepiness after treatment with nasal continuous positive airway pressure.

Sleep-related disordered breathing continuum ranging from simple snoring to obstructive sleep apnea (OSA). Upper airway resistance syndrome (UARS) occupies an intermediate position between these extremes. Note areas of overlap among the conditions.

In this polysomnogram summary graph, obstructive sleep apnea (OSA) severity and the degree of oxygen desaturation (SpO2%) worsen in rapid eye movement (REM) sleep (the black underlined sections) compared with non-REM sleep. This is often the case in OSA patients, especially in OSA patients with comorbid lung disease.

MRI rendering of a patient without obstructive sleep apnea (OSA) (left panel) and a patient with OSA (right panel).

Top image is 3-dimensional surface renderings of the upper airway demonstrating the effect of progressive increases in continuous positive airway pressure (CPAP) from 0-15 cm of water on upper-airway volume in a patient with upper airway narrowing. CPAP significantly increases airway volume in the retropalatal (RP) and retroglossal (RG) regions. Bottom image is soft tissue images in the same patient in the RP region at analogous levels of CPAP. With increasing CPAP, the upper airway progressively enlarges, particularly in the lateral dimension. Note the progressive thinning of the lateral pharyngeal walls as the level of CPAP increases. Little movement occurs in the parapharyngeal fat pads, the white structures lateral to the airway. The first image in each series depicts the baseline upper airway narrowing present in this patient.

Potential relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and the metabolic syndrome. OSAHS has been associated with 3 of the 5 major clinical abnormalities associated with the metabolic syndrome, which is hypertension, insulin resistance, and proinflammatory/oxidative stress. OSAHS may be contributing to and/or modulating the severity of these metabolic abnormalities.

The Mallampati Classification is illustrated. The airway class is based on this visual heuristic.

Tonsil grades.

Obstructive sleep apnea. Note the absence of flow (red arrow) despite paradoxical respiratory effort (green arrow).

Central sleep apnea (thick areas). Note the absence of both flow and respiratory effort (green double arrows).

Comparison of a central apnea (box) and obstructive apnea (circle).

Mixed sleep apnea. Note that the apnea (orange arrow) begins as a central apnea (effort absent; red double arrow) and ends as an obstructive apnea (effort present; green double arrow). Note the arousal (blue arrow) that terminates the apnea and the desaturation (purple arrow) that follows.

A 2-minute recording of sleep showing 4 hypopneas (thick arrows) and associated oxygen desaturations (red arrows). This recording illustrates the recurrent nature of the sleep-disordered breathing observed in many patients.

Effect of nasal continuous positive airway pressure (CPAP) on oxygen saturation in sleep apnea. The upper portion of this figure shows the raw oxygen saturation trace from 1 night of a sleep study. Below the raw trace are vertical lines that indicate the presence of either an apnea or hypopnea. Before CPAP, frequent respiratory events with significant desaturations occurred. During the night, CPAP was applied, resulting in the elimination of the apnea and hypopneas and normalization of the oxygen trace.

Examples of good (upper panel) and poor (lower panel) compliance. In the upper panel, the patient is using continuous positive airway pressure (CPAP) most nights and generally for more than 4 hours (solid black line). In the lower panel, the patient is using CPAP infrequently and, when used, is wearing the CPAP device for less than 4 hours.

Approach to a patient with excessive daytime sleepiness after treatment with nasal continuous positive airway pressure.