OSAHS is defined on the basis of nocturnal and daytime symptoms as well as sleep study findings. Diagnosis requires the patient to have (1) either symptoms of nocturnal breathing disturbances (snoring, snorting, gasping, or breathing pauses during sleep) or daytime sleepiness or fatigue that occurs despite sufficient opportunities to sleep and is unexplained by other medical problems; and (2) five or more episodes of obstructive apnea or hypopnea per hour of sleep (the apnea-hypopnea index [AHI], calculated as the number of episodes divided by the number of hours of sleep) documented during a sleep study. OSAHS also may be diagnosed in the absence of symptoms if the AHI is above 15. Each episode of apnea or hypopnea represents a reduction in breathing for at least 10 sec. OSAHS is often identified when associated with a ≥3% drop in oxygen saturation and/or a brain cortical arousal. OSAHS severity is based on the frequency of breathing disturbances (AHI), the amount of oxygen desaturation with respiratory events, the duration of apneas and hypopneas, the degree of sleep fragmentation, and the level of daytime sleepiness.
During inspiration, intraluminal pharyngeal pressure becomes increasingly negative, creating a “suctioning” force. Because the pharyngeal airway has no bone or cartilage, airway patency is dependent on the stabilizing influence of the pharyngeal dilator muscles. Although these muscles are continuously activated during wakefulness, neuromuscular output declines with sleep onset. In patients with a collapsible airway, the reduction in neuromuscular output results in transient episodes of pharyngeal collapse (manifesting as an “apnea”) or near collapse (manifesting as a “hypopnea”). The episodes of collapse are terminated when ventilatory reflexes are activated and cause arousal, thus stimulating an increase in neuromuscular activity and opening of the airway. The airway may collapse at various levels: the soft palate (most common), tongue base, lateral pharyngeal walls, and/or epiglottis (Fig. 319-1). OSAHS may be most severe during REM (rapid eye movement) sleep, when neuromuscular output to the skeletal muscles is particularly low, and in the supine position due to gravitational forces.
Common sites of airway collapse. For example, the palate, tongue, and/or epiglottis (Ep) can be posteriorly displaced, and the lateral pharyngeal walls (LW) can collapse.
Individuals with a small pharyngeal lumen require relatively high levels of neuromuscular innervation to maintain patency during wakefulness and thus are predisposed to excessive airway collapsibility during sleep. The airway lumen may be narrowed with enlargement of soft tissue structures (tongue, palate, and uvula) due to fat deposition, increased lymphoid tissue, or genetic variation. Craniofacial factors such as mandibular retroposition or micrognathia, reflecting genetic variation or developmental influences, also can reduce lumen dimensions. In addition, lung volumes influence the caudal traction on the pharynx and consequently the stiffness of the pharyngeal wall. Accordingly, low lung volume in the recumbent position, which is particularly pronounced in the obese, contributes to collapse. A high degree of nasal resistance (e.g., due to nasal septal deviation or polyps) can contribute to airway collapse by increasing the negative intraluminal suction pressure. High-level nasal resistance also may trigger mouth opening during sleep, which breaks the seal between the tongue and the teeth and allows the tongue to fall posteriorly and occlude the airway.
Pharyngeal muscle activation is integrally linked to ventilatory drive. Thus, factors related to ventilatory control, particularly ventilatory sensitivity, arousal threshold, and neuromuscular responses to CO2, contribute to the pathogenesis of OSAHS. A buildup in CO2 during sleep activates both the diaphragm and the pharyngeal muscles, which stiffen the upper airway and can counteract inspiratory suction pressures and maintain airway patency to an extent that depends on the anatomic predisposition to collapse. However, pharyngeal collapse can occur when the ventilatory control system is overly sensitive to CO2, with resultant wide fluctuations in ventilation and ventilatory drive and in upper airway instability. Moreover, increasing levels of CO2 during sleep result in central nervous system arousal, causing the individual to move from a deeper to a lighter level of sleep or to awaken. A low arousal threshold (i.e., awaken to a low level of CO2 or ventilatory drive) can preempt the CO2-mediated process of pharyngeal muscle compensation and prevent airway stabilization. A high arousal threshold, conversely, may prevent appropriate termination of apneas, prolonging apnea duration and oxyhemoglobin desaturation severity. Finally, any impairment in the ability of the muscles to compensate during sleep can contribute to collapse of the pharynx. The relative contributions of risk factors vary among individuals. Approaches to the measurement of these factors in clinical settings, with consequent enhancement of “personalized” therapeutic interventions, are being actively investigated.
Risk Factors and Prevalence
The major risk factors for OSAHS are obesity and male sex. Additional risk factors include mandibular retrognathia and micrognathia, a positive family history of OSAHS, genetic syndromes that reduce upper airway patency (e.g., Down syndrome, Treacher-Collins syndrome), adenotonsillar hypertrophy (especially in children), menopause (in women), and various endocrine syndromes (e.g., acromegaly, hypothyroidism).
Approximately 40–60% of cases of OSAHS are attributable to excess weight. Obesity predisposes to OSAHS through the narrowing effects of upper airway fat on the pharyngeal lumen. Obesity also reduces chest wall compliance and decreases lung volumes, resulting in a loss of caudal traction on upper airway structures. Obese individuals are at a fourfold or greater risk for OSAHS than their normal-weight counterparts. A 10% weight gain is associated with a >30% increase in AHI. Even modest weight loss or weight gain can influence the risk and severity of OSAHS. However, the absence of obesity does not exclude this diagnosis.
The prevalence of OSAHS is two- to fourfold higher among men than among women. Factors that predispose men to OSAHS include android patterns of obesity (resulting in upper-airway fat deposition) and relatively great pharyngeal length, which exacerbates collapsibility. Premenopausal women are relatively protected from OSAHS by the influence of sex hormones on ventilatory drive. The decline in sex differences in older age is associated with an increased OSAHS prevalence in women after menopause.
Variations in craniofacial morphology that reduce the size of the posterior airway space increase OSAHS risk. The contribution of hard-tissue structural features to OSAHS is most evident in nonobese patients. Identification of features such as retrognathia can influence therapeutic decision-making.
OSAHS has a strong genetic basis, as evidenced by its significant familial aggregation and heritability. For a first-degree relative of a patient with OSAHS, the odds ratio of having OSAHS is approximately twofold higher than that for someone without an affected relative.
OSAHS prevalence varies with age, from 2–15% among middle-aged adults to >20% among elderly individuals. There is a peak due to lymphoid hypertrophy among children between the ages of 3 and 8 years; with airway growth and lymphoid tissue regression during later childhood, prevalence declines. Then, as obesity prevalence increases in middle life and women enter menopause, OSAHS again increases.
The prevalence of OSAHS may be especially high among patients with diabetes or hypertension. Individuals of Asian ancestry appear to be at increased risk of OSAHS at relatively low levels of body mass index, possibly because of the influence of craniofacial risk factors that narrow the nasopharynx. In the United States, African Americans, especially children and young adults, are at higher risk for OSAHS than their Caucasian counterparts. In a majority of adults with OSAHS, the disorder is undiagnosed.
The precise onset of OSAHS is usually hard to identify. A person may snore for many years, often beginning in childhood, before OSAHS is identified. Weight gain may precipitate an increase in symptoms, which in turn may lead the patient to pursue an evaluation. OSAHS may become less severe with weight loss, particularly after bariatric surgery. Marked increases and decreases in the AHI are uncommon unless accompanied by weight change.
APPROACH TO THE PATIENT: Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS)
An evaluation for OSAHS should be considered in patients with symptoms of OSAHS and one or more risk factors. Screening also should be considered in patients who report symptoms consistent with OSAHS and who are at high risk for OSAHS-related morbidities, such as hypertension, diabetes mellitus, and cardiac and cerebrovascular diseases. SYMPTOMS AND HISTORY
When possible, a sleep history should be obtained in the presence of a bed partner. Snoring is the most common complaint; however, its absence does not exclude the diagnosis, as pharyngeal collapse may occur without tissue vibration. Gasping or snorting during sleep may also be reported, reflecting termination of individual apneas with abrupt airway opening. Dyspnea is unusual, and its absence generally distinguishes OSAHS from paroxysmal nocturnal dyspnea, nocturnal asthma, and acid reflux with laryngospasm. Patients also may describe frequent awakening or sleep disruption, which is more common among women and older adults. The most common daytime symptom is sleepiness. This symptom can be difficult to elicit and may be hard to distinguish from exercise-related fatigue, deconditioning, and malaise. In contrast to true sleepiness, the latter symptoms generally improve with rest. Other symptoms include a dry mouth, nocturnal heartburn, diaphoresis of the chest and neck, nocturia, morning headaches, trouble concentrating, irritability, and mood disturbances. Several questionnaires that evaluate snoring frequency, self-reported apneas, and daytime sleepiness can facilitate OSAHS screening. The predictive ability of a questionnaire can be enhanced by a consideration of whether the patient is male or has risk factors such as obesity or hypertension. PHYSICAL FINDINGS
Physical findings often reflect the etiologic factors for the disorder as well as comorbid conditions, particularly vascular disease. On examination, patients may exhibit hypertension and regional (central) obesity, as indicated by a large waist and neck circumference. The oropharynx may reveal a small orifice with crowding due to an enlarged tongue, a low-lying soft palate with a bulky uvula, large tonsils, a high arched palate, and/or micro/retrognathia. Since high-level nasal resistance can increase pharyngeal collapsibility, the nasal cavity should be inspected for polyps, septal deviation, and other signs of obstruction. Because patients with heart failure are at increased risk for both OSAHS and CSA, a careful cardiac examination should be conducted to detect possible left- or right-sided cardiac dysfunction. Evidence of cor pulmonale suggests severe OSAHS or a comorbid cardiopulmonary condition. A neurologic evaluation is needed to evaluate for conditions such as neuromuscular and cerebrovascular diseases, which increase OSAHS risk. LABORATORY FINDINGS Diagnostic Findings
Since symptoms and signs do not accurately predict the severity of sleep-related breathing disturbances, specific diagnosis and categorization of OSAHS severity require objective measurement of breathing during the period of sleep. The gold standard for diagnosis of OSAHS is an overnight polysomnogram (PSG). A negative in-laboratory PSG rules out OSAHS except in unusual circumstances—e.g., with insufficient REM sleep or supine sleep. Home sleep tests that record only a few respiratory and cardiac channels commonly are used as a cost-effective means for diagnosing patients without significant comorbidity who have a high pretest probability of OSAHS. However, a home study may yield a false-negative result if sleep time is not accurately estimated, and further evaluation may therefore be required.
The key physiological information collected during a sleep study for OSAHS assessment includes measurement of breathing (changes in airflow, respiratory excursion), oxygenation (hemoglobin oxygen saturation), body position, and cardiac rhythm. In addition, PSGs and some home sleep studies measure sleep continuity and sleep stages (by electroencephalography, chin electromyography, and electro-oculography), limb movements (by leg sensors), and snoring intensity. This information is used to quantify the frequency and subtypes of abnormal respiratory events during sleep as well as associated changes in oxygen saturation, arousals, and sleep stage distributions. Tables 319-1 and 319-2 define the respiratory events scored and the severity guidelines employed during a sleep study. Figure 319-2 shows examples of sleep-related respiratory events. A typical sleep study report provides quantitative data such as the AHI and the profile of oxygen saturation over the night (mean, nadir, time at low levels). Reports may also include the respiratory disturbance index, which includes the number of respiratory effort–related arousals in addition to the number of apneas plus hypopneas. In-laboratory PSG also quantifies sleep latency (time from “lights off” to first sleep onset), sleep efficiency (percentage of time asleep relative to time in bed), arousal index (number of cortical arousals per hour of sleep), time in each sleep stage, and periodic limb movement index. OSAHS severity can be further characterized according to the degree of sleep fragmentation associated with respiratory disturbances. Relevant metrics include the frequency of cortical micro-arousals or awakenings per sleep hour, reduction in sleep continuity (low sleep efficiency), reduction of time in deeper stages of sleep (stage N3 and REM sleep) and increases in light sleep (stage N1). The detection of autonomic arousals, such as surges in blood pressure, changes in heart rate, and abnormalities in cardiac rhythm, also provides relevant information on OSAHS severity. Other Laboratory Findings
Various imaging studies, including cephalometric radiography, MRI, CT, and fiberoptic endoscopy, can be used to identify anatomic risk factors for OSAHS. Cardiac testing may yield evidence of impaired systolic or diastolic ventricular function or abnormal cardiac structure. Overnight blood pressure monitoring often displays a “non-dipping” pattern (absence of the typical 10-mmHg fall during sleep from blood pressure while awake). Arterial blood gas measurements made during wakefulness are usually normal. Waking hypoxemia or hypercarbia suggests coexisting lung disease or hypoventilation syndrome. Patients with severe nocturnal hypoxemia may have elevated hemoglobin values. A multiple sleep latency test or a maintenance of wakefulness test can be useful in quantifying sleepiness and helping to distinguish OSAHS from narcolepsy.
TABLE 319-1Respiratory Event Definitions |Favorite Table|Download (.pdf) TABLE 319-1 Respiratory Event Definitions
Apnea: Cessation of airflow for ≥10 sec during sleep, accompanied by:
Persistent respiratory effort (obstructive apneas, Fig. 319-2A), or
Absence of respiratory effort (central apneas, Fig. 319-2B)
Hypopnea: A ≥30% reduction in airflow for at least 10 sec during sleep that is accompanied by either a ≥3% desaturation or an arousal (Fig. 319-2C)
Respiratory effort–related arousal (RERA): A partially obstructed breath that does not meet the criteria for hypopnea but provides evidence of increasing inspiratory effort (usually through pleural pressure monitoring) punctuated by an arousal (Fig. 319-2D)
Flow-limited breath: A partially obstructed breath, typically within a hypopnea or RERA, identified by a flattened or “scooped-out” inspiratory flow shape (Fig. 319-3)
TABLE 319-2Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS): Quantification and Severity Scale |Favorite Table|Download (.pdf) TABLE 319-2 Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS): Quantification and Severity Scale
Apnea-hypopnea index (AHI): a Number of apneas plus hypopneas per hour of sleep
Respiratory disturbance index (RDI): Number of apneas plus hypopneas plus RERAs per hour of sleep
Mild OSAHS: AHI of 5–14 events/h
Moderate OSAHS: AHI of 15–29 events/h
Severe OSAHS: AHI of ≥30 events/h
|aEach level of AHI can be further quantified by level of sleepiness and associated hypoxemia. |
A. Obstructive apnea. There are 30 sec of no airflow, as shown in the nasal pressure (n. p. flow) and thermistor-measured flow (t. flow). Note the presence of chest-abdomen motion, indicating respiratory effort against an occluded airway. B. Central apnea in a patient with Cheyne-Stokes respiration due to congestive heart failure. The flat chest-abdomen tracings indicate the absence of inspiratory effort during the central apneas. C. Hypopnea. Partial obstruction of the pharyngeal airway can limit ventilation, leading to desaturation (a mild decrease in this patient, from 93% to 90%) and arousal. D. Respiratory effort–related arousal (RERA). Minimal flow reduction terminated by an arousal (Ar) without desaturation constitutes a RERA. EEG, electroencephalogram; EOG, electro-oculogram; EKG, electrocardiogram.
Example of flow limitation. The inspiratory flow pattern in a patent airway is rounded and peaks in the middle. In contrast, a partially obstructed airway exhibits an early peak followed by mid-inspiratory flattening, yielding a scooped-out appearance.
Health Consequences and Comorbidities
OSAHS is a major contributor to cardiac, cerebrovascular, and metabolic disorders as well as to premature death. It is the most common medical cause of daytime sleepiness and negatively influences quality of life. This broad range of health effects is attributable to the impact of sleep fragmentation, cortical arousal, and intermittent hypoxemia on vascular, cardiac, metabolic, and neurologic functions. OSAHS-related respiratory events stimulate sympathetic overactivity, leading to acute blood pressure surges during sleep, endothelial damage, and nocturnal as well as daytime hypertension. OSAHS-related hypoxemia also stimulates release of acute-phase proteins and reactive oxygen species that exacerbate insulin resistance and lipolysis and cause an augmented prothrombotic and proinflammatory state. Inspiratory effort against an occluded airway causes large intrathoracic negative pressure swings, altering cardiac preload and afterload and resulting in cardiac remodeling and reduced cardiac function. Hypoxemia and sympathetic-parasympathetic imbalance also may cause electrical remodeling of the heart and myocyte injury.
OSAHS can raise blood pressure to prehypertensive and hypertensive ranges, increase the prevalence of a non-dipping overnight blood pressure pattern, and increase the risk of resistant hypertension. Elevations in blood pressure are due to augmented sympathetic nervous system activation as well as alterations in the rennin–angiotensin–aldosterone system and fluid balance. Treatment of OSAHS with nocturnal continuous positive airway pressure (CPAP) has been shown to reduce 24-h ambulatory blood pressure. Although the overall impact of CPAP on blood pressure levels is relatively modest (averaging 2–4 mmHg), larger improvements are observed among patients with high AHIs and sleepiness.
CARDIOVASCULAR, CEREBROVASCULAR, AND METABOLIC DISEASES
Among the most serious health consequences of OSAHS is its impact on cardiac and metabolic functions. Strong epidemiologic evidence indicates that OSAHS significantly increases the risk of coronary artery disease, heart failure with and without reduced ejection fraction, atrial and ventricular arrhythmias, atherosclerosis and coronary artery disease, stroke, and diabetes. Treatment of OSAHS has been shown to reduce several markers of cardiovascular risk, improve insulin resistance, decrease the recurrence rate of atrial fibrillation, and improve various outcomes in patients with active cardiovascular disease. Large-scale trials are under way to evaluate the role of OSAHS treatment in reducing cardiac event rates and in prolonging the survival of patients with cardiac disease.
More than 50% of patients with moderate to severe OSAHS report daytime sleepiness. Patients with OSAHS symptoms have a twofold increased risk of occupational accidents. Individuals with elevated AHIs are involved in motor vehicle crashes as much as seven times more often than persons with normal AHIs. Randomized controlled trials have shown that treatment of OSAHS with nasal CPAP therapy alleviates sleepiness as measured by either questionnaire or objective testing. However, the degree of improvement varies widely. Residual sleepiness may be due to several factors, including suboptimal treatment adherence, insufficient sleep time, other sleep disorders, or prior hypoxic-mediated damage in brain areas involved in alertness. Visceral adipose tissue, whose amounts are increased in patients with OSAHS, releases somnogenic cytokines that may contribute to sleepiness. Thus, even after treatment, it is important to assess and monitor patients for residual sleepiness and to evaluate the necessity of optimizing treatment adherence, improving sleep patterns, and identifying other disorders contributing to sleepiness.
Reductions in health-related quality of life are common in patients with OSAHS, with the largest decrements on the physical and vitality subscales. Treatment with CPAP often results in improvement in these patient-reported outcomes. Depression, in particular symptoms of somatic depression (irritability, fatigue, lack of energy) is commonly reported in OSAHS.
TREATMENT Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS)
A comprehensive approach to the management of OSAHS is needed to reduce risk factors and comorbidities. The clinician should seek to identify and address lifestyle and behavioral factors as well as comorbidities that may be exacerbating OSAHS. As appropriate, treatment should aim to reduce weight; optimize sleep duration (7–9 hours); regulate sleep schedules (with similar bedtimes and wake times across the week); encourage the patient to avoid sleeping in the supine position; treat nasal allergies; increase physical activity; eliminate alcohol ingestion within 3 h of bedtime; and minimize use of sedating medications. Patients should be counseled to avoid drowsy driving.
CPAP is the standard medical therapy with the highest level of evidence for efficacy. Delivered through a nasal or nasal-oral mask, CPAP works as a mechanical splint to hold the airway open, thus maintaining airway patency during sleep. An overnight CPAP titration study, performed either in a laboratory or with a home “autotitrating” device, is required to determine the optimal pressure setting that reduces the number of apneas/hypopneas during sleep, improves gas exchange, and reduces arousals. Rates of adherence to CPAP treatment are highly variable (average, 50–80%) and may be improved with support by a skilled health care team who can address side effects (Table 319-3). Despite the limitations of CPAP, controlled studies have demonstrated its beneficial effect on blood pressure, alertness, mood, and insulin sensitivity. Uncontrolled studies also indicate a favorable effect on cardiovascular outcomes, cardiac ejection fraction, atrial fibrillation recurrence, and mortality risk.
Oral appliances for OSAHS work by advancing the mandible, thus opening the airway by repositioning the lower jaw and pulling the tongue forward. These devices generally work better when customized for patient use; maximal adaptation can take several weeks. Efficacy studies show that these devices can reduce the AHI by ≥50% in two-thirds of individuals, although these data are based largely on patients with mild OSAHS. Side effects of oral appliances include temporomandibular joint pain and tooth movement. Oral appliances are most often used for treating patients with mild OSAHS or patients who do not tolerate CPAP. However, since adherence to the use of oral appliances sometimes exceeds CPAP adherence, these devices are under investigation for treatment of more severe disease.
Upper airway surgery for OSAHS is less effective than CPAP and is mostly reserved for the treatment of patients who snore, have mild OSAHS, and cannot tolerate CPAP. Uvulopalatopharyngoplasty (removal of the uvula and the margin of the soft palate) is the most common surgery and, although results vary greatly, has a success rate similar to or slightly lower than treatment with oral appliances. Upper airway surgery is less effective in severe OSAHS and in obese patients. Success rates may be higher for multilevel surgery (involving more than one site/structure) performed by an experienced surgeon, but the selection of patients is an important factor and relies on careful targeting of culprit areas for surgical resection. Bariatric surgery is an option for obese patients with OSAHS and can improve not only OSAHS but also other obesity-associated health conditions. Other procedures that can decrease snoring but have minimal effects on OSAHS include injection of the soft palate (resulting in stiffening), radiofrequency ablation, laser-assisted uvulopalatoplasty, and palatal implants.
Supplemental oxygen can improve oxygen saturation, but there is little evidence that it improves OSAHS symptoms or the AHI.
TABLE 319-3Side Effects of Continuous Positive Airway Pressure (CPAP) and their Treatments |Favorite Table|Download (.pdf) TABLE 319-3 Side Effects of Continuous Positive Airway Pressure (CPAP) and their Treatments
|Side Effect ||Treatment |
|Nasal congestion ||Provide heated humidification, administer saline/steroid nasal sprays |
|Claustrophobia ||Change mask interface (e.g., to nasal prongs), promote habituation (i.e., practice breathing on CPAP while awake) |
|Difficulty exhaling ||Temporarily reduce pressure, provide bilevel positive airway pressure |
|Bruised nasal ridge ||Change mask interface, provide protective padding |
|Aerophagia ||Administer antacids |