Article about sleep apnea in adults
Obstructive sleep apnea syndrome (OSAS) affects around 2–4% of the adult population and is characterized by recurring episodes of upper airway (UA) obstruction during sleep. Obstructive apnea results from the inability of UA dilating muscles towithstand the high collapsing forces generated in the pharynx during inspiration, usually as a result of UA narrowing. Apneas are typically terminated by brief arousals, which result in marked sleep fragmentation and account for the major daytime symptoms of excessive sleepiness and cognitive dysfunction found in these patients. OSAS is also an independent risk factor for cardiovascular disease, particularly hypertension.
The diagnosis of OSAS is based on the combination of compatible clinical features and diagnostic sleep studies. While polysomnography represents the gold standard diagnostic test, these studies require major resources; limited sleep studies that focus on recording cardiorespiratory variables are preferred in many cases. The management of moderate and severe OSAS largely centers on nasal continuous positive airway pressure (CPAP), but milder cases can often be managed by conservative measures, including weight loss, alcohol avoidance, relief of nasal congestion, and positional measures to avoid the supine position. A mandibular advancement device is an alternative to CPAP in mild to moderate cases.
The obstructive sleep apnea syndrome (OSAS) is a clinical syndrome marked by recurring episodes of upper airway (UA) obstruction that lead to markedly reduced or absent airflow, referred to as hypopnea and apnea, respectively. These episodes are typically accompanied by loud snoring and hypoxemia, and are usually terminated by transient arousals that result in marked sleep fragmentation and diminished amounts of the deeper stages of sleep, particularly slow wave and rapid eye movement (REM) sleep.
Patients with OSAS are usually unaware of such arousals, but the resulting deterioration in sleep quality contributes significantly to the prominent symptom of excessive daytime sleepiness. However, despite having these significant breathing abnormalities during sleep, most patients have no readily detectable respiratory abnormality while awake. This article will focus on the pathophysiology and clinical manifestations of the disorder, but will not address treatment, since this aspect is covered in other articles.
The prevalence of OSAS has been variously estimated at between 1% and over 6% of the adult population. One comprehensive epidemiological study of prevalence in a general adult population in North America found that 9% of women and 24% of men had an apnea index (AI) greater than 5 h1, but this estimate of prevalence fell to 2% of women and 4% of men when an AI45 was combined with symptomatic daytime sleepiness. These findings underline the importance of not viewing OSAS in terms of AI or apnea/hypopnea index (AHI) alone.
The central feature of obstructive sleep apnea syndrome is recurring obstruction of the UA during sleep and factors predisposing to such obstruction are outlined in Table 1. These factors represent anatomical or pathophysiological abnormalities that result in increased resistance and/or collapsibility of the UA. Anatomical factors generally result in UA narrowing whereas pathophysiological factors generally impair the efficiency of UA dilating muscle contraction. For example, obesity, which is probably the most common predisposing factor, results in UA narrowing by increased fat deposition in the pharyngeal walls and external compression by superficially located fat masses.
Anthropometric (male sex, age, obesity)
Genetic factors (e.g., reduced upper airway (UA) caliber)
Drugs (ethanol, hypnotics)
Upper airway (UA) narrowing
Increased UA resistance
Increased UA compliance
Upper airway muscle function
Ineffective UA dilator muscle activity
Impaired relationship of UA muscle and diaphragm contraction
Reduced chemical drives
Diminished response to negative pressure
Feedback from the lungs
Impaired arousal responses
Postapneic hyperventilation with subsequent reduction in respiratory
Genetic factors also play a role and OSAS is more common in family members. In particular, relatives of nonobese OSAS patients have a smaller UA and a different craniofacial morphologic structure than matched controls. Apparently healthy offspring of patients with OSAS demonstrate impaired respiratory responses to resistive loading during sleep and the hypoxic ventilatory response may be blunted in families with affected members. The supine position predisposes to OSA by gravitational forces that result in posterior displacement of the tongue. Ethanol ingestion is well known to increase the frequency and duration of apneas. This effect results from a combination of a reduction in UA dilating muscle activity and a depressant effect on the reticular activating system, which impairs arousal. Similar effects have been reported with diazepam.
Physiology and Pathophysiology
Oropharyngeal patency is dependent on the action of dilator muscles that contract in a rhythmic fashion coordinated with each inspiration. The pharynx is subjected to collapse when the negative airway pressure generated by inspiratory activity of the diaphragm and intercostal muscles exceeds the force produced by these muscles. A narrowed UA is very common among sleep apnea patients, which leads to increased pharyngeal resistance with the generation of more negative pharyngeal pressures during inspiration.
This narrowing requires an increase in pharyngeal dilator muscle contraction to maintain airway patency. OSAS patients demonstrate more forceful contraction of these muscles while awake than normal subjects but show a larger decrement in contractile forces during sleep, thus contributing to the development of obstructive apnea. Nonetheless, OSAS patients develop at least as forceful pharyngeal dilator muscle contraction during sleep as normal subjects, thus reinforcing the fact that UA obstruction is a result of an imbalance between pharyngeal collapsing forces and dilator muscle contraction rather than a primary deficiency in muscle contraction. However, the sustained increase in dilator muscle contraction in OSAS may predispose to fatigue of these muscles, which could aggravate the tendency to pharyngeal occlusion.
The importance of negative intrapharyngeal pressure as a stimulus to dilator muscle contraction is reinforced by studies of the impact of nasal continuous positive airway pressure (CPAP) on pharyngeal muscle function. CPAP results in a marked decrement in both tonic and phasic contraction of the genioglossus muscle, which allows resting of these muscles and may contribute to the therapeutic benefit of CPAP. Local UA neuromuscular reflexes play a significant role in maintaining pharyngeal patency and there is evidence of defects in these reflexes in patients with OSAS.
Definition of Sleep Apnea Syndrome
The definition of OSAS has evolved over the past 3 decades from an exclusive focus on apnea frequency to a realization that hypopneas and symptom level can be equally important in assessing disease severity. An important development in the definition of OSAS was the report of a Working Group of the American Academy of Sleep Medicine published in 1999, which laid out the clinical criteria necessary for the diagnosis of a clinically significant sleep apnea syndrome and also proposed a grading of severity. In this report, a diagnosis of OSAS requires that the patient report excessive daytime sleepiness together with at least two other compatible symptoms that are not better explained by other factors in addition to the objective demonstration of at least five obstructed breathing events per hour of sleep during sleep studies.
When interviewing a patient with suspected OSAS it is highly desirable to interview their partner as well who can usually provide important additional information based on direct observation of the patient while asleep (Table 2).
|Witnessed apneas||Impaired work/school performance|
|Restless sleep||Morning headache|
|Recurrent arousals||Impaired concentration|
|Nocturnal choking||Impaired memory|
|Enuresis (particularly children)||Heartburn|
Snoring Almost all patients with OSAS snore, usually very loudly. Population surveys indicate that 25% of men and 15% of women habitually snore and the prevalence of habitual snoring increases progressively with age. These data indicate that, while most patients with OSAS snore, only a small proportion of those who habitually snore have OSAS.
These have been shown to be a good diagnostic predictor of OSAS but do not help in predicting severity of the disorder.
Many patients with OSAS report waking at night with a choking sensation, which can be alarming and likely reflects outright wakening during an episode of obstructive apnea. The choking almost invariably passes within a few seconds of wakening.
While OSAS patients rarely have difficulty falling asleep, many report recurring wakenings during the night, which likely reflects the disturbing effect on sleep of recurring arousal. Other nocturnal symptoms Several other nocturnal symptoms may be reported by patients or their bed partner such as nocturia, enuresis, frequent arousals, diaphoresis, and impotence.
Excessive daytime sleepiness
Although sleep apnea is the most common cause of excessive daytime sleepiness (EDS), the severity of EDS and sleep apnea correlate poorly, which may reflect the fact that other disorders can cause EDS. It is important to distinguish fatigue from sleepiness in this context since many patients may confuse the two symptoms.
Other daytime symptoms
OSAS is reported to be associated with many symptoms other than EDS such as fatigue, memory impairment, poor concentration, intellectual deterioration, personality changes, morning nausea, morning headaches, heartburn, automatic behavior, and depression.
Obesity is very common in OSAS, particularly upper body obesity, and there is evidence that patients with OSAS often have fat necks.
Anatomical factors that predispose to UA narrowing should be sought in patients with suspected OSAS, such as retrognathia, micrognathia, tonsillar hypertrophy, macroglossia, and inferior displacement of the hyoid. However, the most common physical finding in patients with OSAS is a non-specific narrowing of the oropharyngeal airway, with or without an increase in soft tissue deposition.
The finding of hypertension in a patient with symptoms suggestive of OSAS increases the likelihood of the disorder.
In clinical practice, the suspicion of OSAS is usually based on a combination of supportive features but it is generally not possible to predict the severity of the disorder based on clinical features, except at the extremes of the clinical spectrum. Thus, some form of objective monitoring during sleep is necessary to confirm and grade the severity of the disorder.
Overnight polysomnography represents the standard for the diagnosis of OSAS since this investigation provides detailed information on sleep state and respiratory and gas exchange abnormalities, in addition to a range of other variables including body position, heart rate and rhythm, and muscle tone and contraction. An example of an obstructive apnea is given in Figure 2. However, these studies are complex and require major resources since they are usually performed in a sleep laboratory under the direct supervision of a trained technician. Thus, it is common to encounter long waiting lists for diagnostic sleep studies in sleep centers throughout the world.
The high prevalence figures for OSAS make it necessary to consider other simplified approaches to the diagnosis. The development of many limited diagnostic systems in recent years represents recognition of these logistic difficulties.Most of these limited systems focus on recording cardiorespiratory variables, without recording sleep state. These systems are particularly useful in the investigation of patients at the extremes of the clinical spectrum, namely to confirm the diagnosis in patients with relatively severe OSAS and to exclude a major degree of OSAS in loud snorers who do not have a clinical presentation suggestive of significant OSAS. Unfortunately, there is no uniformity among these limited systems and the only consistent variable common to these systems is oxygen saturation (SaO2 ). Detailed SaO2 analysis is often sufficient to diagnose OSAS in severe cases because of the characteristic pattern of repetitive desaturations. However, more complete sleep studies are often necessary in patients with mild to moderate disease.
The very large numbers of patients presenting for assessment of possible OSAS have also focused attention on the role of home-based sleep studies. While there are obvious advantages of such studies, particularly improved sleep quality and cost savings, there are also disadvantages. The lack of technician supervision means that leads that become dislodged are not replaced during the study, and consequently the likelihood of technically unsatisfactory studies is higher.
Morbidity and Mortality Related to Sleep Apnea Syndrome
The morbidity of OSAS relates principally to the cardiovascular system. However, this population of patients also has a high incidence of other coexisting cardiovascular risk factors such as obesity, hyperlipidemia, increased age, male sex, smoking history, and excessive alcohol intake, which makes the identification of a clear independent association of OSAS with cardiovascular disease more difficult. Nonetheless, there is now convincing evidence from many studies of an independent association of OSAS with hypertension and this association has been reinforced by recent studies demonstrating a reduction in blood pressure levels with nasal CPAP therapy. A growing body of evidence also points to an independent link between OSAS and ischemic heart disease and stroke.
The mechanisms by which OSAS predisposes to cardiovascular disease are not fully understood but probably include elevated sympathetic drive secondary to recurrent hypoxias and arousals from sleep, in addition to lipid dysfunction, platelet and endothelial cell dysfunction, and insulin resistance. There is emerging evidence that the intermittent hypoxia (IH) that is characteristic of OSA particularly predisposes to the selective activation of proinflammatory transcription factors such as nuclear factor kappa B (NF-kB) with consequent increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-a), interleukin 6 (IL-6), and interleukin 8 (IL-8). These cytokines have been linked to the pathogenesis of atherosclerosis and hypertension.
Recent randomized placebo controlled trials have demonstrated clear objective benefits of CPAP therapy on blood pressure levels. Apart from hypertension, there are limited data to support a significant impact of treatment on cardiovascular morbidity although there is emerging evidence of a reduction in death rate from cardiovascular disease among OSAS patients successfully treated with CPAP.
Association of Sleep Apnea with Road Traffic Accidents
The relationship of OSAS to road traffic accidents has been recognized for many years. Various studies have demonstrated an increase in accident rate between 3 and 7 times that of the general population among untreated OSAS patients, which falls to normal levels after successful therapy with CPAP. There is also evidence that occupations such as long-haul truck driving are particularly associated with an increased risk of accident, particularly where there is evidence of associated OSAS. The risk of accident calls into question the suitability of untreated OSAS patients to hold a driving license and several countries have introduced regulations in this regard. However, patients with OSAS who are successfully treated do not pose a significantly increased accident risk.
Management of OSAS
The management of OSAS is dealt with in other articles and will not be discussed in detail here. Nasal CPAP represents the most widely employed intervention, particularly in moderate to severe cases. Surgery has a limited role to play in the management of OSAS unless there is a specific correctable anatomic lesion. A mandibular advancement device is best suited to mild to moderate cases. An overview of potential management strategies is given below.
Management options for OSAS
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