Snoring

Snoring is the most frequent nocturnal symptom of OSA, occurring in up to 95% of patients with the condition. Snoring has poor predictive value owing to a high prevalence in the general population. In population surveys, the prevalence of snoring increases progressively with age, yet snoring is a hallmark of OSA, and in its absence, the diagnosis of OSA is unlikely. Snoring occurs after sleep onset, although in some patients with OSA it is present even during drowsiness. Its intensity increases with nighttime alcohol consumption and use of sedative drugs. In general, snoring is loudest in the supine position (dorsal recumbency) and decreases in volume in the side-lying position. Periods of silence interrupting loud snoring may reflect occurrence of pathologic apneas.

Other Nocturnal Signs and Symptoms

Patients with OSA usually fall asleep quickly, although many of them report insomnia and frequent nocturnal awakenings. Insomnia is most likely to reflect the perception of recurrent arousals from sleep and its nonrestorative pattern. Repetitive episodes of airway obstruction can be associated with snorting, gasping, diaphoresis, and restlessness that lead to sleep fragmentation. In severe OSA, choking is reported by more than 30% of patients. Nocturnal awakenings raise a differential diagnosis that should include nocturnal asthma, cardiac failure, and gastroesophageal reflux. Pathologic nocturia (2 episodes or more per night) has a prevalence of 50% among patients with OSA. It is thought to be secondary to hypoxia and atrial stretch, leading to increased atrial natriuretic peptide secretion and subsequent increment in intravascular volume. Effective therapy with continuous positive airway pressure (CPAP) reduces occurrence of these symptoms, thus suggesting a causal relationship between them and OSA.

Bed partners often volunteer witnessing breathing pauses followed by snorting or gasping during sleep, and this is a common reason for referral of the patient to a sleep clinic. Witnessed apneas are considered a good diagnostic predictor of OSA; nevertheless, this finding does not correlate with objective measurements and hence does not predict the severity of the disorder.

Excessive Daytime Sleepiness

Sleepiness is difficult to define and is a subjective feeling of impairment of concentration and increased craving for sleep. Excessive daytime sleepiness (EDS) is a nonphysiologic complaint that is not satisfied by a restorative sleep. Sleepiness is reported by 30% to 50% of the general population, so EDS alone is a poor predictor of OSA and requires a differential diagnosis to exclude many other medical conditions associated with this daytime symptom, such as depression, fibromyalgia, chronic insomnia, or hypothyroidism. Patients with OSA sometimes refer to EDS as abnormal daytime tiredness or lack of energy and convey the impression that they must make stringent efforts to remain alert and awake. It is believed that the loss of the restorative function of sleep due to repetitive arousals is the main mechanism to explain the presence of EDS in OSA. The Epworth Sleepiness Scale (Box 61-2) is the most popular tool for subjective evaluation (self-assessment) of EDS. A score above 10 of 24 is considered to be clinically relevant. The relationship between the Epworth score and the apnea-hypopnea index (AHI) (as a surrogate index of OSA severity) is relatively poor. In fact, 35% patients with severe OSA identified within sleep clinics do not complain of EDS. This discrepancy is partly due to underestimation or intentional underreporting the severity of sleepiness for personal gain, such as to avoid job loss. On the other hand, patients scoring high in the Epworth scale could have just mild to moderate OSA. EDS is the most disabling symptom among patients with OSA. One example is drowsiness while driving, which is associated with a three-fold increase in risk of accidents in patients with OSA. Poor school or job performance also is frequently reported.

Other Daytime Signs and Symptoms

On wakening in the morning, half of sufferers report headaches. Morning headache usually is generalized and lessens as the patient begins the usual activities of the day. This symptom may be due to hypercapnia and associated cerebral vasodilatation with resultant increase in intracranial pressure. Often, morning headaches disappear after effective treatment of OSA. Symptoms related to cognitive impairment such as memory loss, irritability, personality changes, and depression are frequent but nonspecific. Both sleep fragmentation and nocturnal hypoxemia have been advocated to explain decreased vigilance and psychomotor impairment, respectively. One concern is the observation that OSA treated with CPAP causes only partial resolution of those deficits, suggesting a potentially irreversible anoxic brain damage. In men with OSA, sexual dysfunction including impotence and decreased libido have been reported in 30% to 50% of the cases and appears to be fully reversible with effective treatment of the OSA. Past medical history should be obtained, particularly for those conditions that may occur as a result of OSA, such as hypertension, cardiac failure, myocardial infarction, and motor vehicle crashes.

Polysomnography

Polysomnography records neurophysiologic and cardiorespiratory signals, to assess sleep stage. Monitoring includes electroencephalography (EEG), electromyography (EMG) of the anterior tibialis, electrocardiography (ECG), oronasal airflow, snoring, thoracic, and abdominal movements, pulse oximetry, and body position (Figure 61-2). The PSG study must be performed in sleep laboratories by trained technicians and is therefore costly and time-consuming but provides the physician with information on both breathing- and non–breathing-related sleep disorders. PSG should be the preferred diagnostic sleep test for snorers with a lower likelihood of OSA, patients with EDS that could be caused by other non–breathing-related disorders during sleep (e.g., narcolepsy, restless legs syndrome), and patients with other medical comorbid conditions (e.g., neuromuscular, cardiac, and respiratory disorders). Apneas and hypopneas are identified, and the number of events per hour of sleep—the apnea-hypopnea index (AHI)—is determined. An AHI of less than 5 is normal. The severity of OSA is classified according to the AHI as mild (5 to 15 events/hour), moderate (15 to 30 events/hour), or severe (more than 30 events/hour). This disease severity classification is correlated with fatal and nonfatal cardiovascular outcomes.

Figure 61-2 Polysomnography tracings showing repetitive obstructive apneic episodes. ECG, electrocardiogram; EEG, electroencephalogram; EMG, electromyogram; EOG, electrooculogram.

Patients with OSA who are considered candidates for CPAP treatment (see further on) need to have a second attended PSG to determine the optimal level of CPAP to abolish the occurrence of all respiratory events. The so-called split night study combines a diagnostic PSG followed by CPAP titration during the same night. It is an accepted alternative to full-night PSG if the AHI is greater than 40 events/hour during the first two hours of recording.

Unattended Sleep Studies

For hospitalized patients or for persons unable to attend a sleep laboratory, PSG can be performed as an unattended study (type 2 study of the AASM classification). Indications and technical requirements are the same as for type 1 (in-laboratory PSG). Type 3 patient monitors are increasingly used owing to the limited number and capacity of sleep laboratories, as well as the increasing number of persons suspected of having OSA. These devices do not monitor EEG and sleep stages but should record the minimum airflow, respiratory effort, and O₂ saturation (Figure 61-3). They cannot evaluate sleep time or detect respiratory event-related arousals. As a result, they tend to underestimate the AHI. On the other hand, for most patients, home sleep studies offer greater convenience, and the study conditions allow close replication of the usual nighttime sleep pattern. The diagnosis of OSA is confirmed and severity determined using the same criteria as for PSG. Type 4 home monitors record continuous single or dual signals during sleep, including O₂ saturation and/or airflow (Figure 61-4). Baseline values for SaO₂, mean SaO₂, nadir SaO₂, and O₂ desaturation index (number of episodes of desaturation greater than 3% as divided by recording time) can be collected very easily using home oximetry. Airflow recorders also assess the frequency of apneas and hypopneas, but differentiation between obstructive and central or mixed apneas cannot be achieved.

Figure 61-3 Type 3 portable monitor: Recorder tracings showing typical obstructive apneas. Channels included are (top to bottom) body movement, abdominal motion, oronasal airflow, pulse rate, and oxygen saturation. EMG, electromyogram.

Figure 61-4 Type 4 portable monitor: Example of apneic events recording obtained with a dual sensor using a nasal cannula and a pulse oximeter applied at the patient’s home. Channels are (top to bottom) airflow, snoring, pulse rate, and oxygen saturation.

The utility of type 3 and type 4 studies is greater for diagnosis of OSA in patients with high pretest probability of moderate to severe OSA and not combined sleep or major medical disorders. In most sleep units, however, use of a home monitor recording oxygen saturations, pulse rate, and airflow, calculating the number and severity of apneas, is a perfectly adequate screening test. If done before the patient sees the clinician, it may suffice or may indicate that a more sophisticated sleep study is needed. A negative result with a portable monitor in patients with symptoms or clinical features highly consistent with OSA also warrants in-laboratory PSG.

Other Evaluations

Once the diagnosis of OSA is made, collaboration with an ear, nose, and throat (ENT) specialist may be valuable to search for anatomic obstruction and to formulate a personalized therapy for each patient. Further blood sample analysis or imaging techniques may not be necessary if additional medical conditions are not suspected, although thyroid function abnormalities can still be present without clinical symptoms. In addition, the patient’s drug history should be reviewed carefully, because many medicines such as opioids, hypnotics, antidepressants, or antihistamines can cause or aggravate sleep apneas.

General Measures

Treatment options should be offered in the context of the severity of the patient’s OSA, risk factors, associated comorbid conditions, and personal wishes. A flow diagram outlining a treatment algorithm is shown in Figure 61-5. All affected patients should avoid alcohol and sedatives, because these agents reduce upper airway muscle tone and increase severity of OSA.

Figure 61-5 Treatment algorithm for obstructive sleep apnea (OSA). This flow diagram shows a general approach to the management of patients with suspected OSA. See Box 61-2 for the Epworth Sleepiness Scale. AHI, apnea-hypopnea index; PAP, positive airway pressure.

Weight loss reduces the collapsibility of the upper airway. It has been shown that a 1% reduction in weight is associated with a 3% decrease in AHI in severe OSA. Currently, weight loss is not a primary treatment for OSA but is recommended as an adjunct to other primary therapies and measures such as CPAP. For patients with mild OSA in whom apneas occur only in the supine position and without daytime sleepiness, positional therapy (e.g., with appropriate use of pillows or placement of a tennis ball at the back) may be of benefit. A type 3 or 4 home monitor can evaluate the efficacy of weight loss or positioning measures. No other medical therapies are recommended as primary treatment for OSA of any severity.

Surgical Treatment

The goal of upper airway surgical procedures is to increase upper airway patency. Surgery remains controversial for the treatment of OSA and is not widely used. A recent Cochrane review concluded that the available evidence does not support the use of surgery for patients with OSA. Nevertheless, it could be indicated if a specific airway abnormality is found. The AASM has identified three potential conditions for the application of upper airway surgery:

Tonsillectomy or adenoidectomy (or in combination) is the primary treatment for children but does not improve OSA in adults. In patients with craniofacial abnormalities, procedures such as mandibular or genioglossus advancement with tongue and hyoid suspension can be effective when performed by expert surgeons. Uvulopalatopharyngoplasty (UPPP) reduces soft palate redundancy and can be used in patients with mild OSA with retropalatal obstruction. Even in these patients, UPPP reduces AHI to less than 50% of baseline. In patients with hypopharyngeal obstruction or severe OSA, UPPP is not effective at all. Hypopharyngeal procedures such as tongue reduction and tongue advancement or stabilization can be considered in patients with macroglossia or hypopharyngeal obstruction, but again these procedures should be performed by experienced surgeons. Nasal surgery—septoplasty, nasal polypectomy, turbinate reduction, and others—should be considered as adjunctive therapy to increase tolerance to CPAP.

Postsurgical follow-up evaluation should include a sleep study to objectively assess the procedure’s success. Further surgical specific outcomes to be evaluated include side effects, complications, anatomic results, patient and spousal satisfaction, and resolution of sleepiness.

Oral Appliances

The aim with use of OAs is to increase upper airway patency and reduce its collapsibility by improving muscle tone. Most OA devices cover upper and lower teeth and hold the mandible in an advanced position with respect to the resting position. This positioning, in turn, pulls the tongue forward, making pharyngeal collapse with consequent obstruction much less likely to happen. An OA ideally should be custom-made for the patient after a dental consultation (Figure 61-6); when created using this approach, the device is much more likely to be beneficial.

Figure 61-6 Oral appliance.

(From Douglas NJ: Obstructive sleep apnea. In Albert RK, Spiro SG, Jett JR, editors: Clinical respiratory medicine, ed 3, Philadelphia, 2008, Mosby.)

In clinical trials, OAs are less efficacious at reducing AHI but are associated with better compliance than that typical for CPAP. Available data regarding long-term outcomes with use of these appliances in persons with OSA are limited. No variables predictive of success have been identified, although OAs work better in persons with mild to moderate OSA, but not so well in those with big heavy jaws and masseters, which can generate forces sufficient to destroy the appliance. Also many persons with OSA grind their teeth during sleep; this bruxism also can destroy the appliance. Thus, sleep studies (e.g., with a home monitor) after treatment are recommended to document the efficacy of these devices. Currently, OAs are indicated for persons with simple snoring, patients with mild to moderate OSA, and those unable or unwilling to use CPAP.

Positive Airway Pressure

Positive airway pressure (PAP) currently is the management modality of choice for patients with OSA. PAP works by providing pneumatic splinting of the upper airway (Figure 61-7). In randomized trials, PAP delivered in continuous mode (i.e., CPAP) has been shown to improve quality of sleep, relieve daytime sleepiness, support maintenance and recovery of neurocognitive and driving abilities, decrease arterial hypertension, and help maximize quality of life in patients with OSA. It also reduces the frequency of cardiovascular events as long-term outcomes in prospective observational studies (Figure 61-8).

Figure 61-7 Anatomic changes with use of continuous positive airway pressure (CPAP) in obstructive sleep apnea. Left, Obstruction of the upper airway at the retrolingual level. Right, CPAP works by splinting and dilating the obstructed pharyngeal segment.

Figure 61-8 Effect of continuous positive airway pressure (CPAP) on mortality. Cumulative incidence of fatal cardiovascular events in patients with untreated obstructive sleep apnea-hypopnea (OSAH) and treated OSAH with CPAP.

(From Marin JM, Carrizo SJ, Vicente E, et al: Long-term cardiovascular outcomes in men with obstructive sleep apnoea/hypopnoea with or without treatment with continuous positive airway pressure: an observational study, Lancet 365:1046–1053, 2005.)

To determine optimal PAP level, a full-night attended PSG study is the preferred approach for titration. A split-night sleep study, however, may be indicated when AHI higher than 40 is recorded during the initial two hours of PSG. Auto-CPAP (aCPAP) machines continually adjust the applied pressure depending on the patency of the upper airway. Such devices may be used in an unattended setting to determine a fixed CPAP pressure, but this option is valid only for patients without significant comorbid conditions or other non-OSA sleep disorders. When high PAP pressure is required to avoid obstruction, the patient receiving CPAP or aCPAP therapy may experience difficulty with exhaling or can develop hypoventilation. In such cases, a switch to a bilevel system (BiPAP) will allow independent adjustment of inspiratory and expiratory pressures, potentially improving tolerance to the therapy.

PAP usually is delivered by nasal mask. Other interfaces such as nasal pillows or full face masks are alternatives to increase patient comfort, ensure a good seal, and avoid leaks. Long-term adherence is predicted by patient sleepiness, average nightly use within the first weeks of therapy, and the reporting of problems during the titration night. PAP is safe, and adverse events are minor and reversible. The most common side effect of PAP is nasal irritation and dryness, which can be treated with an integral heated humidifier. After initial PAP setup, follow-up evaluation is recommended at least once a year and whenever needed to troubleshoot device problems and to assess the cause of any change in clinical features.

Adjunctive Therapies

In obese patients, bariatric surgery may be an acceptable adjunctive therapy in the management of OSA. This surgical procedure is indicated for subjects with a body mass index (BMI) of 40 kg/m² or greater or those with a BMI of 35 kg/m² or greater with important comorbid conditions. Data from cohort studies show that AHI decreases with weight loss after surgery. If previously initiated, PAP should be maintained after surgery as long as it is indicated (see further on).

Oxygen therapy alone is not recommended for patients with OSA. Such therapy provided during sleep could be added to PAP treatment if, during PAP titration, O₂ was needed to correct hypoxemia in patients with cardiopulmonary comorbidity. No effective drugs are available for treatment of OSA. Use of topical nasal steroids may be beneficial adjunctive therapy in patients with rhinitis and frequently improves nasal suffusion, which many patients complain of during CPAP therapy. Modafinil can be used to relieve residual sleepiness in patients who remain sleepy despite effective PAP treatment.

Effects of Treatment on Major Outcomes

In patients with moderate to severe OSA, maxillofacial surgery is the only surgical procedure for which the degree of improvement in sleepiness achieved was similar to that obtained with CPAP in a randomized trial. No effect on other major clinical outcomes such as motor vehicle crashes or incident cardiovascular events in patients with sleep apnea has been evaluated after surgical procedures or with the use of OAs.

In short-term randomized studies, CPAP reduced blood pressure in patients with severe OSA. This effect was evident only in patients who used the machine for more than 5 hours per night. In specific hypertensive populations such as patients with OSA plus resistant hypertension, CPAP also is effective, but again, the treatment must be used for more than 5 hours per night. The long-term effect of therapy to reduce new-onset hypertension in previously normotensive patients with OSA has not yet been determined. In population and clinic-based long-term observational studies, treatment with CPAP in patients with severe OSA is associated with reduced risk for development of fatal and nonfatal cardiovascular events (i.e., myocardial infarction, stroke). A reduction in frequency of motor vehicle crashes among persons with severe OSA treated with CPAP also has been noted. Today, however, with respect to assessment and validation of the effect of treatment, good long-term randomized controlled trials with strong end points such as cardiovascular events, traffic accidents, or all-cause mortality are lacking. Attempting these kinds of studies poses ethical problems in patients with significant daytime sleepiness: Because CPAP is very effective in alleviating this symptom, it cannot be denied for a long time in a control group.

Whom to Treat and How

Untreated patients with moderate to severe OSA have an increased risk for involvement in motor vehicle crashes and cardiovascular events. Current evidence indicates that persons with excessive daytime sleepiness (e.g., with an Epworth Sleepiness Scale score higher than 10), or who fall asleep while driving to or at work, should be treated no matter what the AHI is. For these patients, PAP is the primary treatment. For patients with AHI greater than 30, CPAP also is indicated as primary treatment regardless of the degree of sleepiness. For those with mild to moderate OSA (AHI between 5 and 30), therapy with CPAP is effective, but OAs and upper airway surgery should be offered and the risks and expected benefits discussed with the patient. Use of OAs is more suitable for thinner and younger patients with mild OSA. Surgery should be limited to patients with mild to moderate OSA who refuse other forms of therapy or as adjunctive treatment for those with upper airway obstruction to improve tolerance to PAP.

Obstructive Sleep Apnea in Women

As in chronic obstructive pulmonary disease (COPD), OSA remains underdiagnosed in women. Physicians have a lower suspicion of OSA in females. On the other hand, they are more reluctant than males to complain of snoring. Finally, women reported more sleep and medical comorbidities such as depression, fibromyalgia, hypothyroidism, or chronic fatigue syndrome that ultimately can be attributed as responsible for daytime sleepiness. Hence, the clinicians need to include OSA in their differential diagnosis when evaluating female patients.

Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease

The coincidence of OSA and COPD is termed overlap syndrome, and it is present in 1% of adults older than 40 years of age. In patients with OSA alone, daytime hypoxemia is rare, but in patients with COPD, the coexistence of OSA is associated with more profound nocturnal hypoxemia than in patients who have only one disorder. Consequently, patients with the overlap syndrome are at high risk for development of pulmonary hypertension. Recently, these patients have been reported to be at increased risk for severe exacerbations of COPD and all-cause mortality compared with patients with COPD and no coexistent OSA. Moreover, treatment of the OSA component of the overlap syndrome with CPAP decreases COPD exacerbations and improves survival. Accordingly, it is paramount in patients with COPD and daytime sleepiness to evaluate the potential coexistence of OSA.

Sleep Laboratory Versus Out-of-Laboratory Diagnosis

Full overnight polysomnography remains the “gold standard” modality for the diagnosis of sleep-disordered breathing performed in a staffed laboratory setting. Out-of-laboratory diagnosis is rapidly growing in respiratory medicine. The utility of these studies is greatest among patients with high pretest probability of severe disease, who may benefit from expedited diagnosis and treatment. Nevertheless, uncertainty remains regarding the quality of most devices, and pitfalls in automatic scoring have been recognized. Currently, portable systems for the diagnosis of OSA should be applied only by trained physicians, and their use should be limited to patients with suspected OSA not associated with comorbid conditions or other sleep disorders unlikely to be a cause of symptoms.

Non–continuous Positive Airway Pressure Therapy

Despite the efficacy of CPAP for relieving symptoms of OSA, many patients experience discomfort with this therapy and look for a curative option. Evidence supports the use of OAs in persons with mild to moderate OSA and weight loss in obese patients. Nevertheless, most surgical therapies lack robust scientific evidence and cannot be recommended as treatment for severe OSA. Controversies exist on when and what procedure to perform on an individual basis. Success depends mainly on the experience of the surgeon.