What every physician needs to know:
Obstructive sleep apnea (also known as sleep apnea hypopnea, particularly outside North America) is a common disorder: population-based studies in the U.S. have shown a prevalence in the general, working-age population of roughly 9 percent of women and 24 percent of men. The prevalence rises with advancing age and, in women, after passing through menopause. Infants and children also can manifest OSA, with overall prevalence estimated at around 3 percent.
Obstructive sleep apnea (OSA) is a laboratory diagnosis based on demonstrating a minimum number of apneas plus hypopneas per hour of sleep (apnea hypopnea index, or AHI). The obstructive sleep apnea syndrome (OSAS or sleep apnea hypopnea syndrome, SAHS) is the diagnosis when a patient has OSA plus signs or symptoms consistent with OSA pathogenesis. In adults, the most common symptoms are snoring, witnessed breathing cessations during sleep, excessive sleepiness, awakening headaches, nocturnal awakenings, and (less commonly) awakenings with shortness of breath, gasping, choking, or a snoring sensation. The most common signs are systemic hypertension and type 2 diabetes mellitus (T2DM) or glucose intolerance.
Except for OSA associated with certain rare neurological disorders, OSA is caused by a combination of anatomic and respiratory control derangements. Anatomically, patients with OSA usually exhibit narrowing of the oropharyngeal and/or hypopharyngeal (base of tongue) airway. The narrowing may be the result of obesity with deposits of adipose tissue adjacent to the upper airway, adenotonsillar hypertrophy (especially in children), mandibular deficiency (overjet/retrognathia or relative micrognathia), elongated palate, large uvula, or macroglossia.
Because of these anatomic changes, excessive upper airway dilator muscle tone is required to maintain airway patency. This tone is diminished as a natural consequence of transitioning to sleep from wakefulness, resulting in partial or complete obstruction of the upper airway. As hypoxia and hypercapnia progress from insufficient ventilation, inspiratory effort increases and eventually prompts arousal from sleep. The arousal restores dilator muscle tone, allowing relief of the obstruction and compensatory hyperventilation. The patient then returns to sleep, and the process repeats at intervals throughout the night.
Robust prospective evidence identifies OSA as a risk factor for cardiovascular disease, cerebrovascular disease, and T2DM/glucose intolerance. Prospective randomized controlled trials have also associated OSA with systemic hypertension.
Successful treatment of OSA has been shown in prospective studies to improve T2DM control and glucose intolerance, while retrospective evidence suggests that treatment reduces the incidence of cardiovascular disease and stroke. Treatment of OSA has been shown to lower blood pressure in hypertensive individuals although it is not clear that the degree of improvement, while statistically significant, has clinical relevance.
Symptoms of OSAS, including excessive sleepiness, nocturnal awakenings, and morning headaches, improve with treatment. Many of the sequelae of OSA are now attributed to activation of inflammatory pathways, probably because of intermittent hypoxemia, as evidenced by elevation in such mediators as TNFα and IL-6. The hypersomnia caused by OSA is likely related to sleep disruption from recurrent arousals, although the intermittent hypoxemia may also play a role.
The diagnosis of OSA most commonly involves laboratory polysomnography, which records multiple physiological signals during the patient’s normal sleep period. These signals include electroencephalography (EEG), electro-oculography (EOG), and submental electromyography (EMG), which together identify wakefulness and the four stages of sleep in the adult or older child. Airflow at the nose and mouth, respiratory effort (chest and abdominal movement), a microphone to detect snoring, and pulse oximetry identify respiratory events, while bilateral anterior tibialis EMGs are recorded in order to document leg movements, and a position sensor correlates respiratory events with sleeping posture.
Other signals, such as more channels of EMG if a parasomnia is suspected, may be collected depending on the clinical scenario. Continuous audio-video recording of the patient in bed is also commonly performed. In certain situations, portable monitoring (PM) in the patient’s home, involving the recording of a more limited subset of signals is common. This technology is generally accepted as capable of identifying moderate to severe OSA when a high pre-test probability exists, when no other sleep disorder is suspected, and when significant co-morbidities are absent. These devices usually record only respiratory signals and do not distinguish wakefulness from sleep during the test.
The mainstay of OSA treatment continues to be the application of positive airway pressure during sleep, which acts to splint the upper airway open despite insufficient dilator muscle tone. Continuous positive airway pressure (CPAP) most frequently suffices, while an occasional patient will find bilevel positive airway pressure (bilevel PAP) more comfortable. Bilevel PAP is also used when ventilatory support is felt to be necessary, such as in patients with OSA and obesity hypoventilation syndrome (OHS).
A second night of laboratory polysomnography (the titration night) is frequently required to determine the correct positive airway pressure (PAP) settings, although the diagnostic and titration studies can often be combined into one night of testing, termed a “split night study.” In some patients, oxygen may also be necessary, which is bled into the PAP circuit. Automatically titrating PAP devices are also available, which may be suitable for determining a fixed PAP pressure for subsequent treatment or may be left in the automatic mode indefinitely for ongoing therapy.
Long-term adherence to PAP therapy can be as high as 80 percent, depending on the intensity of follow-up, proper education of the patient in the use of the device, disease severity, and symptomatic response to treatment. Oral appliances, specifically mandibular advancement devices, can be used for first-line therapy in mild disease or as salvage treatment in patients unable to adhere to PAP use. Similarly, a variety of upper airway surgical procedures, particularly uvulopalatalpharyngoplasty (UPPP) can be used to treat mild OSA or as salvage therapy. In obese patients, weight loss can be helpful.
According to the International Classification of Sleep Disorders, 2nd Edition (ICSD-2), there are no identifiable subtypes of OSA. Three types of respiratory events may occur in any given patient with OSA: frank obstructive apneas, characterized by essentially absent airflow despite continued inspiratory effort; hypopneas, with reduced airflow despite continued inspiratory effort, resulting in oxyhemoglobin desaturation and/or arousal from sleep; and respiratory-effort-related arousals, in which increased inspiratory effort maintains normal degrees of airflow despite reduced airway caliber and increased upper airway resistance, but the increased effort results in arousal.
For purposes of syndrome definition, the ICSD-2 does not distinguish among the three types of events. However, many experts consider upper airway resistance syndrome (UARS) a sleep disorder not identical to OSAS. A symptomatic patient who demonstrates a respiratory disturbance index (RDI apneas+hypopneas+RERAs per hour of sleep) greater than a defined threshold (which some authors set at five per hour and others at fifteen per hour), accompanied by a normal AHI, defines UARS in the view of these practitioners.
In younger children (i.e., eight years of age or less), adenotonsillar hypertrophy and craniofacial dysmorphologies constitute the most frequent disorders that predispose to OSA.
Obesity, which may well be considered a disease, is strongly associated with OSA in older children and in adults. The mechanism that leads to the development of OSA in the obese individual remains controversial, with evidence implicating the deposition of adipose tissue adjacent to the upper airway that leads to reduced caliber and changed orientation of the lumen, and other evidence suggesting that abdominal fat deposition (as judged by waist circumference or waist:hip ratio) is the more important factor, possibly mediated by reduced functional residual capacity or altered levels of adipokines.
OSA is highly prevalent in patients with trisomy 21 and in individuals who have undergone surgical repair for a cleft palate. The prevalence of OSA increases in association with certain other disorders (T2DM, stroke, congestive heart failure), but since causality is almost certainly bidirectional between these conditions and obstructive sleep-disordered breathing, they are not currently viewed as OSA subtypes.
A variety of neurological and neuromuscular diseases may also directly cause OSA by inducing weakness of the upper airway dilator muscles. Those reported to cause OSA in this way include amyotrophic lateral sclerosis (ALS), muscular dystrophies, and myasthenia gravis. A few neurological disorders (multiple system atrophy, syringomyelia/syringobulbia) may produce OSA with obstruction at the vocal cords (an atypical site, never involved in idiopathic OSA) or in the more common pharyngeal locations.
Are you sure your patient has obstructive sleep apnea? What should you expect to find?
By far the most common symptom of OSA is snoring. However, population-based studies have shown that even this is not a universally endorsed symptom in polysomnographically proven OSA. For instance, the seminal Sleep Heart Health Study (SHHS) of 5,615 individuals found that 30 percent of subjects with an AHI of five or more per hour considered themselves to be non-snorers.
Much of the difficulty lies in objectively characterizing snoring; it is truly “in the ear of the beholder,” such that one observer’s loud snoring may be another’s normal breathing sounds. Moreover, some individuals live in situations where no one has had the opportunity to listen while they sleep–in the SHHS, 29 percent of the subjects did not know if they snored–so the absence of snoring has uncertain negative predictive value. Snoring also has limited positive predictive value; 30 percent of habitual snorers in the SHHS had a normal AHI lower than five.
Regardless of these uncertainties, the practical clinician will seek additional information with respect to any reported snoring. Intermittent (suggesting the absence of respiratory sounds during apneas), or resuscitative (consistent with compensatory hyperpnea after cessation of a respiratory event) snoring may increase the pre-test probability of OSA.
Arguably, the most common sign of OSA is obesity; approximately 70 percent of patients with OSA are overweight. Here again, however, the presence of a common sign is no guarantee that the disease exists in a given individual. Again referencing the SHHS, 31 percent of the subjects in the highest quartile of body mass index (BMI) had normal values of AHI. That said, weight gain exerts a significant influence on the likelihood of developing OSA. The Wisconsin Sleep Cohort Study (WSCS), a large population-based study of adult working men and women demonstrated that a 10 percent weight gain was associated with an approximately six-fold increase in the odds of developing OSA over the course of four years. The SHHS confirmed this association, albeit with a lesser increase in odds for women compared to men.
Other symptoms, roughly in order of decreasing frequency, include witnessed breathing cessations during sleep, excessive sleepiness, difficulty with concentration and/or memory, headaches upon awakening, feeling sad or blue, frequent nocturnal awakenings (some of which may be associated with shortness of breath, choking, or a snoring sensation), nocturia, sleep-associated symptoms of gastroesophageal reflux (acid brash, heartburn, indigestion), decreased libido in both genders, and erectile dysfunction in men.
The symptom of excessive sleepiness deserves clarification. Although often cited as one of the most common symptoms of OSA, there is considerable variability in the association between sleepiness and severity of OSA, depending on how hypersomnolence is measured. When excessive sleepiness is defined as an Epworth Sleepiness Scale (ESS) score of ten or higher, the SHHS found that only 46 percent of 1,149 subjects with moderate or severe OSA endorsed this symptom. Most, but not all, cross-sectional studies of OSA patients have found a modest correlation between AHI and ESS.
Even when excessive sleepiness is measured more objectively by the multiple sleep latency test (MSLT), a significant minority of patients with OSA in cross-sectional studies exhibit normal results. An early report by Guilleminault et al. found that 24 of one hundred patients with OSA (AHI>10/hour) were not objectively sleepy as defined by a mean sleep latency greater than eight minutes. A more recent study by Punjabi et al. of 741 subjects with an AHI of at least ten per hour demonstrated pathological sleepiness (mean sleep latency<10 minutes) in 79.5 percent overall and in 89.6 percent of the most severe category of patients, those with an AHI of at least sixty per hour. Consequently, an absence of a sleepiness complaint cannot exclude the diagnosis of OSA or even severe OSA in any individual patient.
Other signs, also roughly in order of decreasing frequency, include neck circumference of more than sixteen inches in women and more than seventeen inches in men; oropharyngeal crowding, which is associated with excess posterolateral oropharyngeal tissue, large uvula, or tonsillar hypertrophy; low-lying palate, which is often quantified using the Mallampati score with tongue protruded or a modified Mallampati score without tongue protrusion; narrow, high-arched palate; retruded or small mandible (retrognathia or overjet may or may not be described depending on the presence of any maxillary retrusion); and macroglossia.
Systemic hypertension may be considered a sign of OSA in some patients. Signs of cor pulmonale (pedal edema, ascites, right ventricular heave or gallop, loud P2) may be appreciated if an independent cause of diurnal hypoxemia, such as obesity hypoventilation syndrome or chronic obstructive pulmonary disease, accompanies OHA. Cor pulmonale or significant pulmonary hypertension is rarely seen, even in patients with severe OSA, in the absence of awake hypoxemia.
Because no single sign or symptom can reliably predict the presence of OSA, as defined by an elevated AHI, several predictive models have been developed that take into account combinations of these variables, as well as pertinent demographic information. The most popular predictive model is arguably the Berlin Questionnaire, which takes into account changes in weight, the presence and character of snoring, witnessed pauses in breathing, awakening feeling “tired,” “tiredness” during waking hours, falling asleep driving, and a history of hypertension. The Berlin Questionnaire, which is divided into sections termed “categories,” assigns point values to the responses in each category. The sum of point values for each section determines whether a section is “positive” or “negative”; if at least two categories are “positive,” the pretest probability of diagnosing OSA is considered high.
Comparisons between the Berlin Questionnaire’s determination of an OSA diagnosis and that from subsequent sleep testing have varied widely, even in similar groups of subjects. Positive predictive values (PPV) range from 48 percent to 96 percent, and negative predictive values (NPV) range from 44 percent to 81 percent when an AHI diagnostic threshold of five per hour is used.
The next most popular predictive model appears to be the STOP questionnaire used with the STOP-Bang scoring model to classify pre-operative patients as at high or low risk of OSA. On the STOP instrument, yes/no responses are requested to four questions: loud snoring; tired, fatigued, or sleepy during the daytime; observed breathing cessations during sleep; and history of hypertension. The additional information on the STOP-Bang scoring model consists of yes/no data for BMI greater than 35 kg/m2, age higher than fifty years, neck circumference greater than 40 cm, and male gender. Positive responses to three or more items on the STOP-Bang classify the patient as being at high risk for OSA.
Used as a screening instrument in individuals without a history of a sleep disorder, positive predictive value averages 80 percent, and the negative predictive value averages from 44 percent to 61 percent.
Beware: there are other diseases that can mimic obstructive sleep apnea:
Many diseases are associated with hypoxemia that worsens or occurs only during sleep. Primary pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchial asthma, the multitude of interstitial lung diseases, and pulmonary vascular diseases may all exhibit worsening gas exchange during sleep. The pathogenesis of this phenomenon is often hypoventilation from the reduction in ventilatory drive associated with sleep (especially rapid eye movement sleep, stage R) or loss of the accessory respiratory muscles’ contribution to ventilation, also in stage R.
The accessory muscles of respiration (intercostals, sternomastoids, scalenes, abdominals) are skeletal muscles that participate in the hypotonia of all such muscles, which is a hallmark of stage R. The sleeping posture may also worsen gas exchange by shifting functional residual capacity below closing capacity, in effect increasing shunt fraction as a result of absent ventilation of dependent airways during part of each tidal breath.
Similarly, patients with restrictive chest wall diseases that involve reduced thoracic compliance (e.g., kyphoscoliosis and anklyosing spondylitis), mechanical interference with diaphragmatic descent (e.g., obesity and ascites), or ventilatory muscle weakness (e.g., ALS or muscular dystrophies) may exhibit worsening hypoxemia during sleep. Airway caliber is also known to vary in a circadian manner in many asthmatics, with worsening symptoms at night. Typically, these masqueraders of OSA manifest with symptoms of awakening repeatedly during the night (frequently with dyspnea) or of morning headaches, while snoring and excessive sleepiness are usually not prominent.
A special case involves the so-called “overlap” syndrome, in which patients are afflicted with both COPD and OSA. These disorders may coincide in large part because the prevalence of both increases with age, tobacco smoking, and male gender. Such patients usually voice complaints typical of OSA (snoring, sleepiness), and they have other characteristics (obesity, upper airway findings) that lead to a suspicion of OSA in the normal course of expert management.
Finally, systolic or diastolic left heart failure may engender sleep-associated symptoms of paroxysmal nocturnal dyspnea or orthopnea that must be distinguished from awakenings that are due to OSA.
When excessive sleepiness is the most prominent complain, many causes, not just OSA, must be considered. Insufficient sleep syndrome (not allowing enough time for sleep) is extremely common in modern society, and a careful history of sleep habits is invaluable. The myriad causes of insomnia, many of which are psychiatric or psychological, result in sleep loss and may produce sleepiness, fatigue, or impaired functioning during wakefulness. Narcolepsy and other hypersomnias of neurological origin must also be distinguished from OSA, while recognizing that the elevated incidence of OSA in narcolepsy means that some patients may require diagnosis and treatment of both conditions.
Central sleep apnea (CSA) and associated syndromes share some characteristics with OSA. Two general classifications of CSA, hypercapnic and eucapnic (or hypocapnic), are commonly recognized. Individuals who suffer from the former condition have, by definition, a neurological lesion or neuromuscular disease that leads to the intermittent loss of ventilatory effort during sleep. These patients may complain of nocturnal awakenings with shortness of breath or air hunger, awakening headaches, and excessive sleepiness.
The presence of a known or suspected neurological or neuromuscular disease that manifests as either respiratory muscle weakness or impaired respiratory control should prompt laboratory polysomnography. Such a study will demonstrate periods of apnea associated with absent inspiratory effort characteristic of CSA, and a measurement that reflects arterial pCO2 (end-tidal capnography or transcutaneous CO2 monitoring) will reveal sustained hypercapnia.
Patients with eucapnic or hypocapnic CSA also exhibit central apneas during sleep testing, with or without the waxing and waning Cheyne-Stokes pattern of ventilation. These individuals exhibit reductions in arterial pCO2 during sleep to below the apneic threshold; this reduction inhibits inspiratory effort until pCO2 rises above the threshold and stimulates the return of vigorous inspiratory effort. The cycle of apnea, followed by hyperventilation, followed by another apnea may repeat throughout non-rapid eye movement (NREM) sleep.
Two changes in state produce enough separation between arterial pCO2 and the apneic threshold to suppress periodic breathing in CSA: awakening, which lowers the apneic pCO
2 threshold, and transitioning into stage R, which lowers the respiratory drive and drives arterial pCO2 higher. Eucapnic/hypocapnic CSA may be idiopathic, may occur during acclimatization to high altitude, or (most commonly) may be associated with left-sided congestive heart failure or hemispheric stroke. Snoring is usually mild or absent, but awakenings from sleep with or without dyspnea/air hunger and excessive sleepiness may occur.
The proper diagnosis will be made apparent during laboratory polysomnography, at which point a search for the precipitating disease should be initiated if it is not already known.
Finally, one subtype of obesity hypoventilation syndrome (OHS) may be confused with OSA. Obesity hypoventilation syndrome is diagnosed when an obese patient (conventionally, BMI>30 kg/m2) exhibits diurnal hypercapnia that is not attributable to another respiratory disorder. While it has become apparent that, in many cases of OHS, the pathogenesis is directly related to coexistent OSA, some of these patients (up to half in some small case series) do not exhibit OSA or do not correct their awake hypoventilation after successful OSA treatment.
Other than a dearth of symptoms directly attributable to OSA (e.g., loud snoring, witnessed breathing cessations), such patients may be difficult to differentiate from those with sleep-disordered breathing since they are obese and usually present with a chief complaint of hypersomnia.
How and/or why did the patient develop obstructive sleep apnea?
Obesity is the most prominent epidemiogic characteristic of patients with OSA; approximately 70 percent are overweight. However, almost a third of SHHS subjects in the highest quartile of body mass index (BMI) have normal values of AHI. During childhood and young to middle-aged adulthood, males are far more likely to present with OSA than females. However, once women pass through menopause, the prevalence of OSA rapidly rises and becomes equal to that of men (except among women who receive hormone replacement therapy).
In general, OSA prevalence increases with age until late old age, at which point the likelihood of having OSA plateaus or even declines somewhat, a phenomenon thought to be a “survivor” effect. Certain racial and ethnic groups, specifically those of African or Asian ancestry, demonstrate an elevated prevalence of OSA that is thought to be the result of facial and upper airway morphology in these groups. Similarly, since facial and upper airway morphological characteristics that predispose to OSA are often shared by blood relatives, it is not uncommon to observe familial clusters of the disorder.
Certain medical conditions are known to be associated with an elevated likelihood of diagnosing OSA. Hypertension, congestive heart failure, atrial fibrillation and flutter, cerebrovascular disease, coronary artery disease, T2DM, gout, and renal failure are all distinguishable in this regard. It follows that OSA is a common comorbidity to the metabolic syndrome, which, by definition, combines several of these disorders under one rubric.
Trisomy 21 (Down syndrome) carries an extremely high risk of OSA, and the probability of OSA is raised in individuals with acromegaly, certain facial dysmorphologies (e.g., Treacher-Collins syndrome and Robin sequence) and hypothyroidism. Chronic opioid treatment (e.g., methadone maintenance), and abuse of alcohol or tobacco increase the risk for OSA. Finally, OSA incidence increases in neurological or neuromuscular diseases that produce weakness in the upper airway dilator muscle.
Which individuals are at greatest risk of developing obstructive sleep apnea?
In children, the most common predisposing factors are tonsillar hypertrophy, obesity, specific dysmorphologies/genetic disorders (such as trisomy 21 and Robin sequence) and cleft palate repair. All of these conditions are readily identified by history or physical examination. In the case of dysmorphologies/genetic disorders, chromosomal analysis or genetic testing may be confirmatory. In adults, the prototypical OSA patient is male, of middle age or older, and obese, all of which are evident by history and inspection. However, post-menopausal females approach the same level of risk as males.
Individuals diagnosed with hypertension, congestive heart failure, atrial fibrillation and flutter, cerebrovascular disease (particularly after a stroke), coronary artery disease, T2DM, gout, and renal failure have elevated risk for OSA, so appropriate screening questions should be asked. Regular use of opioids, either by prescription or illicitly, and alcohol abuse should prompt the clinician to investigate for symptoms of OSA. Patients with neurological or neuromuscular disorders with demonstrable or suspected upper airway dilator muscle involvement are also at particular risk for sleep-disordered breathing, which may be obstructive and may have elements of a central pathogenesis.
What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?
There are only a few standard laboratory studies that can be helpful in the care of a patient suspected of having OSA. Because of the higher prevalence of OSA in hypothyroidism, a TSH (if not already available from routine laboratory screening of the adult primary care patient) can be considered. Although the overall yield is low, correction of undiagnosed hypothyroidism can result in improvement of OSA.
A hemoglobin and hematocrit determination is useful in screening for secondary polycythemia, which can sometimes complicate OSA. Serum creatinine and blood urea nitrogen are indicated to exclude chronic kidney disease, which is associated with a high prevalence of OSA, and fasting blood glucose and hemoglobin A1c will help screen for T2DM, another condition associated with OSA. Urine or serum toxicology screening should be pursued if opioid abuse is suspected, and echocardiography may be indicated if pulmonary hypertension or congestive heart failure is suspected (although OSA alone is a cause of only mild to moderate degrees of pulmonary hypertension in most cases).
In patients with BMIs greater than 30 kg/m2, it is helpful to determine whether OHS may be a complicating factor. The combination of normal awake pulse oximetry and CO
2 determination from blood chemistry (in the absence of corticosteroid or diuretic treatment) can reasonably exclude diurnal hypercapnia, although this has not been systematically studied. Sleep laboratories that monitor end-tidal pCO2 (in patients without obstructive airways disease) or transcutaneous pCO2 during NPSG can use these results to discern whether OHS is present. An arterial blood gas measurement can be pursued if any question of OHS remains.
What imaging studies will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
Imaging studies are generally not necessary in the usual patient suspected of having OSA. Radiological chest imaging may aid in diagnosing a comorbid pulmonary or cardiac disorder, and lateral head and neck roengenograms, as commonly performed by orthodontists, can be of use when surgical treatment is elected for OSA, but they are not part of the standard evaluation of such patients.
What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
Pulmonary function testing can be helpful if the “overlap” syndrome or another comorbid pulmonary disorder is suspected. An arterial blood gas determination should be obtained in the patient with a BMI greater than 30 kg/m2 if OHS cannot be excluded otherwise.
What diagnostic procedures will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
Nocturnal polysomnography (NPSG) attended by a skilled technologist in the sleep laboratory remains the “gold standard” for diagnosing OSA in both children and adults. In this test, multiple physiological signals are continuously recorded during the patient’s normal sleep period, most commonly using a variety of noninvasive technologies. Under current American Academy of Sleep Medicine (AASM) guidelines, three derivations of electroencephalography (EEG), bilateral electro-oculography (EOG), and submental electromyography (EMG) are used to classify each thirty-second epoch (or page) of the recording as either predominantly wakefulness or one of the four stages of sleep in the adult or older child.
Airflow at the nose and mouth is measured by thermometry. Thermometry responds to the difference between air inhaled at room temperature and air exhaled at body temperature by detecting changes in pressure sampled at the nares, which reflect the degree and direction of airflow through the resistance of the nasal passages. Respiratory effort is most commonly detected by respiratory inductance plethysmography, which employs elastic bands that contain coils of wire stretched around the chest and abdomen.
A microphone is placed near the jugular notch to detect snoring, and a pulse oximeter measures oxyhemoglobin saturation. Bilateral anterior tibialis EMGs are recorded in order to document leg movements, and a position sensor allows for the correlation of respiratory events with sleeping posture. At least one channel of electocardiography is collected to monitor for arrhythmias that may complicate OSA.
Depending on the clinical scenario, additional signals, such as more channels of EMG if a parasomnia or nocturnal seizure disorder is suspected, may be included, and continuous audio-video recording of the patient in bed is a usual practice. The test may be performed under a full-night diagnostic protocol, or various treatment modalities can be employed to determine the best therapy for the patient.
Therapy most frequently takes the form of a CPAP titration, in which the pressure setting is progressively increased until a value is reached that adequately suppresses all manifestations of OSA. Bilevel PAP orvalidation/titration of adaptive servoventilation or auto-titrating CPAP or bilevel PAP devices may also be performed during NPSG, and an oxygen bleed is sometimes added to PAP devices when necessary because of persistent hypoxemia.
The split-night protocol is often utilized in order to implement more rapid treatment. An initial diagnostic phase, usually lasting at least two hours, is followed by a titration (usually with CPAP) if the patient exhibits a minimum degree of OSA severity. Studies have demonstrated that an AHI of at least twenty per hour during the diagnostic phase will enable an adequate titration during the remainder of the night, although some laboratories will split a study at lower thresholds of AHI.
An NPSG is scored by a skilled technologist who examines the raw data from each epoch and designates each epoch as indicating that the patient is either predominantly awake or in one of the four stages of sleep. The technologist also visually identifies respiratory events, periodic limb movements, and other phenomena using fixed criteria. Since most laboratories utilize computerized polysomnograph equipment, software tabulates the events entered by the technologist and automatically computes and displays summary data after staging and scoring are complete.
An NPSG report conventionally includes the following data under the heading of “sleep architecture”: total recording time, time in bed from “lights out” to “lights on” (TIB), total sleep time (TST), sleep latency (time from “lights out” to the first epoch of sleep), REM latency (time from the first epoch of sleep to the first epoch of stage R), sleep efficiency (TST/TIB expressed in percentage), and the percent of TST spent awake and in each of the four sleep stages. The respiratory parameters on a report include at least AHI and an oxyhemoglobin desaturation index (ODI), usually defined as desaturations of 4 percent or greater, and they often include the lowest saturation associated with a respiratory event, the percentage of TST spent with saturations below a certain level, and average saturation. The saturation data may also be displayed separately for the time spent in non-REM stages and stage R.
An additional degree of complexity has been added in the U.S. when scoring laboratory NPSGs because of rules imposed by CMS. The widely accepted (by CMS, the AASM, and others) definition of an apnea consists of a drop in the maximal thermal sensor (airflow) signal excursion of 90 percent or more from baseline for at least 90 percent of the event duration, and a total event duration of at least ten seconds. For many years, hypopneas were defined based on a specified reduction in airflow, followed by either a desaturation to a certain degree or polysomnographic evidence of an arousal from sleep, or both. However, CMS rules now require that a hypopnea be scored only when associated with at least a 4 percent oxyhemoglobin desaturation, without regard to whether an arousal is present.
When not scoring under CMS requirements, most laboratories employ AASM criteria, in which a hypopnea is identified when the nasal pressure (airflow) signal excursion drops by 50 percent or more from baseline, followed by either a desaturation of 3 percent or more or an arousal, or both; or when the nasal pressure exursion drops by at least 30 percent of baseline, followed by a 4 percent or greater desaturation. In both instances, at least 90 percent of the event duration must meet the drop in amplitude criterion, and the total duration must be ten seconds or longer.
Portable monitoring (PM) in the patient’s home is also an option in certain situations. There are currently two classification systems for PM devices, the historical AASM classification and the more recent CMS system. The AASM historically considered four types of sleep testing:
Type 1: full attended polysomnography (≥ 7 channels) in a laboratory setting
Type 2: full unattended polysomnography (≥ 7 channels)
Type 3: limited channel devices (usually using 4–7 channels)
Type 4: 1 or 2 channels usually using oximetry as 1 of the parameters
More recently, the acceptance of PM by the Centers for Medicare and Medicaid Services (CMS) in the U.S. as a valid tool for the diagnosis of OSA led to a revised classification scheme:
Type II devices, which monitor and record a minimum of seven channels: EEG, EOG, EMG, ECG/heat rate, air flow, respiratory movement/effort, and oxygen saturation
Type III devices, which monitor and record a minimum of four channels: respiratory movement/effort, air flow, ECG/heart rate, and oxygen saturation
Type IV devices, which monitor and record a minimum of three channels, one of which is air flow
Other devices that monitor and record a minimum of three channels, including actigraphy, oximetry, and peripheral arterial tone, and for which there is substantive clinical evidence in the published, peer-reviewed medical literature that demonstrates that the results accurately and reliably correspond to an AHI or RDI. This determination is made on a device-by-device basis. WatchPAT (Itamar Medical) is currently the only approved device in this category.
AASM Type 3 or CMS Types III or IV technologies are usually used. These technologies record a more limited subset of signals than laboratory polysomnography does, and they are generally accepted as capable of identifying moderate to severe OSA when a high pre-test probability exists, when no other sleep disorder is suspected, and when there are no significant co-morbidities. These devices commonly record only respiratory signals, although they may also document body position, heart rate, and leg movements, but most do not monitor EEG, EOG, and EMG, so they cannot distinguish wakefulness from sleep during the test.
Consequently, the AHI that is calculated using this technology uses recording time as the denominator rather than total sleep time, and it may underestimate the true value of this severity index. In addition, PM studies are almost always unattended by a technologist, so there is no opportunity to monitor the quality of the recorded signals and make adjustments to leads and sensors as may become necessary during the course of the night to correct malfunctions. The result is that as much as 20 percent of PM recordings cannot be interpreted because of unacceptable data quality.
Other drawbacks to unattended testing include the loss of opportunity to educate the patient concerning OSA and the ability to convert a test into a split-night protocol that assesses the sleep benefits of CPAP therapy so as to determine proper treatment in one night of recording.
What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
Pathologic, cytologic, and genetic tests are not part of the routine evaluation of patients suspected of having OSA. When a previously undiagnosed genetic or dysmorphologic syndrome is suspected, specific laboratory determinations, such as chromosomal analysis for trisomy 21, may be helpful.
If you decide the patient has obstructive sleep apnea, how should the patient be managed?
Once a diagnosis of OSA is made in the adult, a decision must be made concerning whether to institute an active therapeutic modality or to pursue conservative management. With respect to active treatment, the choices include some form of PAP, an oral appliance, or surgical modification of the upper airway. Conservative management consists of weight loss in the obese individual, sleep-position training if respiratory events occur predominantly in the supine position, and avoidance of risk factors.
The most common identifiable factors that are known to exacerbate OSA are alcohol and respiratory-depressant medications near to bedtime (usually defined as within four hours) and tobacco smoking. Sleep position training can be implemented using commercially available sleeping shirts that incorporate inflatable or solid bumpers along the back of the garment such that individuals who wear the garment find it uncomfortable to sleep while supine and learn over time not to sleep in this position (just as most adults have learned not to roll out of bed while asleep). These sleeping shirts can also be created at home by fabricating a cloth pocket on the back of a pajama top, into which is one or more tennis balls are inserted.
Although there is some evidence that even mild degrees of OSA (as defined by AHI) can be risk factors for cardiovascular disease, stroke, and T2DM, conventional practice is to reserve active treatment for individuals who have least moderately severe disease (AHI of at least per hour), regardless of whether they are symptomatic or have sequelae attributable to OSA, and in mild disease (AHI of at least five per hour but less than fifteen hour) only when symptoms or sequelae are present. This algorithm was initially codified in a CMS National Coverage Decision based on early cross-sectional data from the SHHS and other sources, and it was subsequently adopted by many, if not most, commercial third-party payers.
That said, it remains unclear whether it is entirely safe to withhold active treatment from patients who have mild disease (as defined using either CMS or AASM AHI criteria). Evidence thus far shows that mild OSA may result in anatomic changes in blood vessels that may be an early sign of atherosclerosis, functional changes in the ability of blood vessels to dilate that may indicate early atherosclerosis, abnormalities in coagulation parameters consistent with a pro-thrombotic state, increases in pro-inflammatory cytokines, modest increases in blood pressure, and possible increased incidence of diabetes.
However, the evidence is far from conclusive, particularly when larger cross-sectional studies and large prospective studies are examined. Prospective studies have, for the most part, failed to demonstrate an effect of mild OSA on morbidity and mortality overall, although such a difference may eventually be demonstrated after longer follow-up. One study suggests an interaction between smoking and OSA. Other studies routinely adjust their results for other risk factors and do not mention whether an interaction of these factors with OSA was examined. One prospective study in patients with pre-existing CVD demonstrated increased risk of stroke in untreated mild OSA.
Prospective treatment studies of mild OSA are consistent with an improvement in all patients in event-free survival when treated with CPAP. A prospective study of stroke incidence in patients with mild OSA and pre-existing CVD, as well as studies that demonstrate reduced CVD events in patients with mild OSA who receive CPAP, suggests that treatment of mild OSA in patients with known CVD risk factors is warranted.
Once a decision to treat actively is made, the mainstay of therapy remains PAP, usually CPAP. Originally introduced in the early 1980s, PAP pressurizes the upper airway through a nasal, oronasal, or even oral interface that acts as a “pneumatic stent” to maintain upper airway patency despite insufficient dilator muscle tone. A secondary mechanism may relate to increases in intrathoracic volume induced by positive end-expiratory pressure, which increases “tracheal tug” and expands major airways, although this putative effect remains controversial.
A large variety of interfaces are now available, with new models or improved versions of previous models appearing almost weekly. Choices include nasal or oronasal (full face) masks that incorporate a flexible seal that conforms to the contours of the face; “nasal pillows,” consisting of soft, hollow plugs that fit within the nares; and an oral interface consisting of a mouthpiece with an overlying pliable sealing flap. All are held in place by headgear of varying design, some of which are more amenable to side or prone sleeping than others. Most come in an extensive variety of sizes, as well as narrow to wide ratios of height to width.
The CPAP setting that fully suppresses obstructive sleep-disordered breathing is peculiar to each patient. While the pressure that is required generally increases with higher AHI and BMI values, predictive equations based on AHI, BMI, and other variables have not proven to be sufficiently accurate for clinical use. About 80 percent of patients titrate to a pressure between 8 and 12 cm H2O.
The proper setting is most frequently determined during a full-night NPSG specifically ordered for the purpose of titration or during the titration phase of a split-night NPSG. Since the pressure required to suppress events varies with sleeping posture and stage (higher settings are required in the supine position and in stage R), it is important to confirm, if possible, that the setting recommended from a titration NPSG was effective in supine stage R sleep. An effective pressure can be determined in virtually every patient who is able to sleep while the device is applied.
The most vexing problem with employing CPAP for the treatment of OSA remains that of achieving long-term adherence. Using the widely accepted (and CMS mandated) criterion of at least 70 percent of nights and demonstrating usage of four hours or greater per night, overall adherence rates are believed to range between 50 percent and 80 percent of patients who agree to initiate this therapeutic modality.
A variety of factors have been identified as driving this metric: Side effects from the pressure itself, the flow of air, and the interface are major dissatisfiers. These issues include symptoms that are closely related to the level of pressure, such as mask leaks, aerophagia, the sensation of breathing against pressure, and chest discomfort; symptoms attributable to the amount of airflow necessary to maintain a set pressure, such as nasal congestion, sneezing, rhinorrhea, oral/nasal dessication, and blower noise; and a poorly fitting, uncomfortable, and/or leaking interface.
There are effective measures for ameliorating all of these problems, with the possible exception of complaints about the degree of pressure. The strategy for nasal symptoms and oronasal dryness consists of heated humidification of the airstream, a virtual necessity in dry climates and during the winter in locales subject to cold weather. Topical nasal corticosteroids should be added if humidification does not resolve the nasal symptoms. Switching to an oronasal interface or application of a chin strap are also useful strategies, both of which prevent leakage of air out of the mouth when a nasal interface is used. Mouth leakage causes the CPAP generator to increase airflow in order to maintain the set pressure, which results in more nasal symptoms. The wide variety of interface types and sizes usually allows for the resolution of discomfort or leakage complaints. Aerophagia usually resolves over time, but in the interval, strategies consisting of simethicone at bedtime and side-sleeping can be helpful.
The key to adherence has been demonstrated to involve close follow-up of the patient ,including prompt attention to side effects, encouragement, and education concerning the benefits of treatment. Virtually all CPAP generators (as well as other forms of PAP therapy) are available with sockets for semiconductor memory cards that record adherence data on a night-by-night basis, as well as estimates of mask leak and AHI. Proprietary software allows these data to be downloaded in graphic and tabular formats, furnishing the clinician with objective information as to the patient’s adherence to treatment. (It has been well demonstrated that patients’ self-reported usage grossly overestimates actual adherence.) Such information can be critical in obtaining the best possible compliance with therapy.
Pressure generators that implement expiratory pressure relief, said to aid adherence in patients that complain of a sensation of exhaling against excessive force, are widely available. When enabled, the set pressure is reduced briefly at the start of exhalation to ameliorate this unpleasant perception. Another strategy, applicable when the titration demonstrates much higher pressure requirements while supine compared to other sleeping positions, is to combine sleep position training with the lower CPAP setting that is found to be adequate when the patient is not supine. Other strategies resort to more sophisticated PAP generators: auto-titrating CPAP and bilevel PAP.
Auto-titrating CPAP devices derive information about tidal volume and upper airway obstruction using interface pressure and flow to estimate the patient’s air flow. Each device contains a proprietary algorithm that utilizes these parameters to determine the presence of apneas, hypopneas, and (in some) snoring and inspiratory flow limitation. The CPAP setting is increased or decreased in steps depending on whether sleep-disordered breathing is detected: if a disturbance is detected, pressure is increased by a programmed amount, and if no events are sensed for a set period of time, the pressure is decreased by a programmed amount.
Theoretically, such devices track the pressure requirements of different sleep positions and stages, resulting in lower overall settings. Such devices may be useful when a laboratory titration cannot be performed expeditiously because of scheduling difficulties or lack of access in rural areas. It has been widely proposed that the lower average pressure achieved by auto-titrating CPAP may ameliorate the complaints of excessive pressure voiced by some patients and improve adherence, but most studies have not supported this contention.
Bilevel PAP devices add the ability to detect the respiratory phase and switch between a lower pressure during exhalation and a higher pressure during inspiration. The difference in pressure between inspiration and expiration augments ventilation, acting as a positive pressure ventilator in pressure-support mode. Bilevel PAP has proven useful in patients with hypoventilatory disorders in both the chronic and acute settings. In patients with OSA, sufficient pressure during exhalation (expiratory positive airway pressure, or EPAP) acts to suppress obstructive apneas, while an appropriately higher pressure during inhalation (inspiratory positive airway pressure, or IPAP) eliminates obstructive hypopneas, limitations in inspiratory flow, and snoring.
Thus, titrating an OSA patient with bilevel PAP involves raising EPAP until obstructive apneas are no longer detected and then increasing IPAP to levels above EPAP until hypopneas, flow limitation, and snoring are suppressed. Theoretically, this process results in lower average treatment pressures and better adherence to PAP treatment by some patients. As in the case of auto-titrating CPAP, numerous investigations have not proven this to be the case in OSA patients generally, but many clinicians hold to the belief that certain patients achieve better adherence with auto-titrating CPAP or bilevel PAP. Therefore, such modalities are widely invoked when best efforts have not achieved adherence in individual patients.
It may well be that studies have not been sufficiently powered or designed to identify subclasses of patients who are likely to benefit from any of these pressure-moderating devices. Auto-titrating bilevel PAP generators are also available, but their proper role in the treatment of OSA is not well defined.
During titration in the laboratory, it has been increasingly reported that some patients develop recurrent central apneas as the pressure settings increase. This phenomenon is one type of complex sleep apnea, and a variety of mechanisms have been proposed to explain this finding. At times, it is clear that arousals related to the application of PAP in a patient not accustomed to the device results in a central apnea as sleep is re-entered, since the arterial pCO2 set-point is known to be slightly higher during sleep compared to wakefulness. In other cases, this is a less likely explanation, and other respiratory control system abnormalities have been invoked.
For instance, this phenomenon may be more common in patients with heart failure and related to the central sleep apnea sometimes seen in this condition. Management of this complex sleep apnea is controversial: some have demonstrated that the central apneas resolve over time in more than half of these individuals and that only watchful waiting is recommended, while others advocate adding an oxygen bleed to the PAP, changing to bilevel PAP with or without a backup rate, or resorting to more sophisticated PAP devices, such as adaptive servoventilation. Regardless of the strategy chosen, it is incumbent upon the clinician to demonstrate successful treatment during careful observation of the patient in the sleep laboratory.
Oral appliances are reasonable first-line treatment choices in patients with mild or mild to moderate OSA, and as second-line treatments in patients who simply cannot become adherent to PAP therapy. Mandibular advancement devices, by far the most widely used, engage the upper and lower teeth so as to cause protrusion of the jaw and allow anterior movement of the tongue, increasing the posterior airway space. The appliances can be fitted in one visit to the dentist if a “boil and bite” model is chosen, or one can be custom-fabricated in the dental laboratory after impressions are taken. Recent evidence suggests that the custom devices are more effective. In either case, most appliances can be adjusted after fitting to achieve different degrees of jaw protrusion.
In the patient at risk for sequelae of OSA, it is important to demonstrate efficacy of the appliance during an NPSG. If the device is not effective, the degree of protrusion can often be increased to achieve a more satisfactory response. In general, patients with more severe OSA (higher AHI) or greater degrees of obesity are less likely to be adequately treated with an appliance. In addition, mandibular advancement devices are not recommended in patients with temporomandibular joint disease, and they cannot be used effectively in the edentulous individual. They may also be problematic in other patients with extensive dental pathology.
Adherence to this type of therapy is usually superior to that of PAP, but side effects consist of excessive salivation, temporomandibular joint discomfort, and malocclusion of the bite for a time after removing the appliance in the morning. Even so, the devices are generally well tolerated.
Several surgical techniques have been developed to treat OSA. Tracheotomy was the first effective treatment, but it has now been almost completely supplanted by other modalities. Occasionally, a patient with life-threatening OSA because of cardiac arrhythmia or OHS may still benefit, but tracheotomy is usually resisted by the candidate despite the substantial risk of remaining untreated.
Uvulopalatopharyngoplasty (UPPP) consists of excision of the uvula, tonsils (if present), and redundant posterolateral palatal tissue. It may be accomplished using cold steel or application of the surgical laser. This technique addresses obstruction only at the level of the oropharynx, so it carries a response rate (defined as resulting in an AHI below a certain threshold, usually five, ten, or fifteen per hour) that varies between about 30 percent to 70 percent. As in the case of the mandibular advancement device, patients with higher AHI or BMI are less likely to respond.
Several “base of tongue” procedures have been advocated when the patient is thought to have a significant component of obstruction at this level. Most involve applying anterior traction to or displacement of the hyoid bone, which tends to shift the base of the tongue (which attaches to the hyoid) anteriorally. These procedures are not definitive, but they may add a few percent to the success rate. As with oral appliances, these procedures can be chosen as first-line therapy for the patient with mild OSA or as a second-line therapy when PAP is refused or not tolerated.
The most effective technique involves maxillomandibular osteotomies with fixation of these structures in a more anterior position. The group at Stanford University has reported success rates approaching 100 percent after this more radical procedure, which may not be available in some locations and which represents a considerable commitment by the patient to insisting on a surgical treatment.
All of these procedures carry the usual risks of surgery, including those of anesthesia, pain, bleeding, and infection. In addition, UPPP may result in nasopharyngeal incompetence, causing a change in the voice (rhinolalia aperta) or nasopharyngeal reflux when swallowing. Symptoms of nasopharyngeal incompetence are often temporary and resolve with time. A common strategy is to perform these procedures in a stepwise fashion, from the less radical (UPPP, base of tongue) to the more radical, pausing to assess the efficacy of each step by NPSG before consideration is given to advancing to the next procedure.
Other surgical techniques that have been advocated include laser-assisted uvulopalatoplasty (LAUP), implantation of stiffening devices (the Pillar procedure) into the palate, and radio frequency tissue reduction at various sites in the upper airway. The first procedure is a less extensive form of UPPP, said to be amenable to performance in the office setting in a staged (multiple visit) process. It has proven to be far less effective than UPPP, and in some studies OSA actually worsened. When the technique is performed over the course of multiple visits, many patients do not return for the required number of treatments because of the pain they experience.
The Pillar procedure may be effective for simple snoring and may be marginally effective for mild OSA, but the implants do not always stay in place, and not infrequently they must be re-inserted.
Radio frequency tissue reduction involves placing a needle electrode submucosally at a site through which alternating current electricity is introduced into the tissue to denature proteins local to the electrode. Over time, the tissue shrinks and scars, resulting in a smaller, stiffer structure. The most frequent sites to which this technique is applied are the base of the tongue and the posterolateral oropharynx. Results reported thus far suggest that a very modest response can be obtained in mild OSA. Since the targeted mucosa cannot be disinfected, submucosal infection, although comparatively rare, is the most common complication of this procedure.
Palatal implants and radio frequency tissue reduction have not proven to be useful in general except in patients who will not accept more effective treatment modalities.
Finally, the clinician should not forget to consider bariatric surgery in the morbidly obese patient with OSA, particularly when the patient has rejected or failed at other OSA treatment strategies.
Because of lack of demonstrated efficacy, some medical therapies–selective serotonin uptake inhibitors, estrogen, and nasal decongestants–are not recommended for treatment of patients with OSA. Some evidence suggests modest improvements in AHI with the relief of nasal obstruction using topical corticosteroids. Oxygen, although widely used as a temporary treatment by the primary care community while diagnosis and definitive treatment are pursued, is not recommended; while overall oxygenation may improve with such therapy, the effect on the frequency and duration of obstructive events is unpredictable, and one or both may actually increase.
The treatment of OSA in children is differs significantly in several ways from that in adults. First, the normal AHI in the child is much lower than the normal range commonly used in adults: an AHI higher than 1 on an NPSG is commonly used as one criterion for the diagnosis, and prolonged obstructive hypoventilation, as assessed by end-tidal or transcutaneous pCO2, is an added metric.
Adenotonsillectomy is the primary mode of treatment for children if any degree of tonsillar hypertrophy is evident, as resolution of OSA occurs in about 70 percent of children so treated. However, studies of the natural course of these children following adenotonsillectomy suggests that OSA may recur, particularly if obesity supervenes. If adenotonsillectomy is not effective or not indicated, or if OSA returns, treatment options revert to those used for adults with OSA. However, concerns about alterations in facial anatomy that may occur as a result of the pressure of wearing a PAP interface every night have yet to be comprehensively examined. In addition, there or more surgical and/or orthodontic options for children when OSA can be explained by facial anatomy or a dysmorphology.
What is the prognosis for patients managed in the recommended ways?
Prospective evidence from high-quality population studies identifies OSA as a risk factor for cardiovascular disease (including myocardial infarction, systemic hypertension, and congestive heart failure), stroke, and T2DM/glucose intolerance. Overall mortality, as well as mortality from cardiovascular disease, is also increased in patients with OSA.
A variety of cardiac arrhythmias have been observed in association with sleep-disordered breathing events. They include various brady arrhythmias, which are attributed to vagal stimulation from inhalation against an obstructed airway (the Müller maneuver) and hypoxemia, and ventricular arrhythmias, which are most closely correlated with the degree of hypoxemia but are also thought to be related to increased sympathetic tone following arousal. Despite this association, reports of sudden nocturnal death in OSA are rare.
The prognosis for treated OSA includes amelioration of symptoms like excessive sleepiness and improvement in surrogate endpoints that represent risk factors for morbidity and mortality. Almost all research has focused on CPAP treatment, which has been identified as the treatment most capable of normalizing AHI. Multiple high-quality studies (randomized controlled trials) have demonstrated improvement in both subjective sleepiness (usually using the Epworth Sleepiness Scale score) and an objective measure using the maintenance of wakefulness test (MWT).
The MWT assesses the ability to maintain wakefulness in surroundings that would normally promote sleep by placing the subject in such an environment for four or five forty-minute periods with the instruction to stay awake. Using standard EEG, EOG, and EMG monitoring, the amount of time the individual stays awake before exhibiting the first epoch of sleep is determined. (If no sleep occurs, the value is stated as forty minutes.) The average over all periods reflects the balance between wakefulness-promoting and sleep-promoting central nervous system mechanisms. Objective sleepiness measured using the MSLT has not consistently shown significant improvement after treatment. The difference in these objective measures has strengthened the contention that the MWT and MSLT reflect different aspects of sleep/wake control.
Research that examines surrogate endpoints frequently involves less robust methods, but they have demonstrated with some consistency improvement in quality of life, neurocognitive function, inflammatory and pro-coagulation indices, pulmonary artery pressure, systemic blood pressure, daytime sympathetic tone, ejection fraction in patients with coexisting OSA and congestive heart failure, and measures of insulin sensitivity/T2DM control.
Investigators have paid considerable attention to the effect of CPAP treatment on systemic blood pressure. Most studies have shown improvement in mean blood pressure, with an effect size of around 2 to 4 mmHg; The relatively small magnitude of this effect raises a question concerning whether the improvement is clinically significant.
With respect to morbidity, observational studies consistently show a reduction in motor vehicle accidents, cardiovascular events (myocardial infarction and coronary artery revascularization procedures), and stroke after effective treatment of OSA; the rate of these complications usually approaches that of individuals without OSA. In addition, patients with OSA who undergo electrical cardioversion for atrial fibrillation experience fewer recurrences when the OSA is effectively treated. Finally, observational studies of mortality in CPAP-treated OSA patients have demonstrated that death rates attributable to cardiovascular disease decline to that of patients without OSA.
Few data are available with respect to the effect of treatment modalities other than CPAP. Some evidence shows a reduction in blood pressure in patients treated with mandibular advancement devices. It seems likely that, if other therapies achieve AHIs on treatment similar to that of CPAP, then outcomes will also be similar.
What other considerations exist for patients with obstructive sleep apnea?
The occurrence of familial clusters of OSA suggests that genetic factors may play a role in the development of this disorder. A family history of OSA should increase the clinician’s estimate of pre-test probability of OSA in any given patient. However, there are no extant gene-association studies that correlate with OSA risk.
Misconceptions are still prevalent in the general medical community concerning obstructive sleep apnea. It has been said that “sleep apnea is an epidemic spread by physicians”–that is, that OSA is a normal finding turned into a disease that must be diagnosed and treated by physicians with ulterior motives. Clearly, the weight of evidence from high-quality prospective studies has demonstrated unequivocally that OSA is a serious condition with important adverse sequelae, so this calumny should be laid to rest.
The second misconception is that patients do not adhere to treatment for OSA, particularly PAP therapy, so only little effort is worth expending in treating these patients. Several factors argue against this attitude: First, the fact that patients do not act in accordance with prescribed treatments has been a chronically vexing issue in the delivery of health care, even when compliance requires only swallowing a pill daily. Non-adherence has been estimated to result in enormous losses ($100 billion per year) in the U.S. health system.
Singling out PAP as a therapy not worth ordering because adherence is suboptimal lacks justification. Second, expert management of the patient who is prescribed PAP clearly results in better adherence, with objective measures showing that such management can achieve regular and substantial use of these devices. Finally, there is ample evidence that even suboptimal adherence can improve many important outcomes, not the least of which is cardiovascular mortality.
What’s the evidence?
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. vol. 328. 1993. pp. 1230-5. (This report from the Wisconsin Sleep Cohort Study (WSCS) has become one of the most frequently cited papers in the introduction section of any research paper in the field of OSA. The authors performed a population-based study of working-age adults (30-60 years of age) in Wisconsin. A random sample of state employees completed a questionnaire, and all self-reported habitual snorers and 25 percent of the non-snorers underwent NPSG (a total sample of about 1500 subjects). From these data the authors calculated the prevalences of OSA and OSAS by gender and age. This is one of two ongoing population-based prospective studies of OSA that have formed the bedrock of our knowledge in this field; the other is the Sleep Heart Health Study (Young T, Shahar E, Nieto FJ et al. Predictors of sleep-disordered breathing in community-dwelling adults. The Sleep Heart Health Study. Arch Intern Med 2002; 162:893-900). )
Lumeng, JC, Chervin, RD. “Epidemiology of pediatric obstructive sleep apnea”. Proc Am Thorac Soc. vol. 5. 2008. pp. 242-252. (The authors performed a systematic review and meta-analysis of investigations of the epidemiology of OSA in children. From these data they estimated population prevalences for parent-reported "always" snoring, parent-reported apneic events during sleep, OSA diagnosed using various combinations of parent-reported symptoms on questionnaires, and OSA diagnosed by sleep studies using an assortment of criteria.)
“International classification of sleep disorders: diagnostic and coding manual”. 2005. (The definitive nosology of sleep medicine, listing all of the currently-recognized sleep disorders. Each entry includes concise explications of essential and associated features, demographics, predisposing and precipitating factors, inheritance patterns, clinical course, pathophysiology, laboratory findings, differential diagnosis, and criteria for diagnosis. This is the "bible" for practicing sleep medicine clinicians.)
Young, T, Shahar, E, Nieto, FJ, Redline, S, Newman, AB, Gottlieb, DJ. “Predictors of sleep-disordered breathing in community-dwelling adults.The Sleep Heart Health Study.”. Arch Intern Med. vol. 162. 2002. pp. 893-900. (This article is from the second of two seminal population-based prospective studies (the Sleep Heart Health Study, or SHHS) that continue to add important information to our database on OSA. A cohort of more than five thousand adults was assembled out of studies already in progress on cardiovascular disease in general populations throughout the U.S. These studies included the Atherosclerosis Risk in Communities Study (1,750 participants), the Cardiovascular Health Study (1,350 participants), the Framingham Heart Study (1,000 participants), the Strong Heart Study (600 participants), the New York Hypertension Cohorts (1,000 participants), and the Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants).Type 2 (unattended full NPSG) sleep studies were performed on the participants, who also completed comprehensive questionnaires concerning their sleep habits and symptoms. A variety of sub-studies were also performed in which additional testing (e.g., echocardiography) was obtained on smaller groups of the subjects. Extensive cross-sectional and now prospective information from this cohort has greatly expanded our knowledge base in the field of sleep medicine. This paper reports cross-sectional data on the symptoms, demographics, and anthropomorphic characteristics associated with NPSG-diagnosed OSA.)
Peppard, PE, Young, T, Palta, M, Dempsey, J, Skatrud, J. “Longitudinal study of moderate weight change and sleep-disordered breathing”. JAMA. vol. 284. 2000. pp. 3015-3021. (This report of prospective data from the WSCS demonstrates the four-year incidence of a new diagnosis of OSA and the relationship between changes in weight during the four years and AHI. A 10 percent gain in body weight resulted in an increase in AHI of about one third, and a 10 percent decrease in body weight prompted a decline in AHI by about 25 percent. The odds of developing OSA increased 600 percent with a 10 percent increase in body weight.)
Newman, AB, Foster, G, Givelber, R, Nieto, FJ, Redline, S, Young, T. “Progression and regression of sleep-disordered breathing with changes in weight. The Sleep Heart Health Study.”. Arch Intern Med. vol. 165. 2005. pp. 2408-2413. (Prospective data from the SHHS reports anthropomorphic variables and AHI sampled on entry into the study and five years later. Men experienced a greater increment in AHI than women with similar degrees of weight gain, but no other anthropomorphic or demographic variables had an effect on this relationship. As in the data from the WSCS, weight gain was associated with a greater degree of AHI increase than the fall in AHI that occurred with similar degrees of weight loss. In addition, AHI tended to increase over the five years, even with no change in body weight.)
Patil, SP, Schneider, H, Schwartz, AR, Smith, PL. “Adult obstructive sleep apnea. Pathophysiology and diagnosis.”. Chest. vol. 132. 2007. pp. 325-337. (One of a series of review articles published in CHEST over the last few years that summarize what is currently known about the pathogenesis of OSA, diagnostic strategies, and clinical course.)
Punjabi, NM, O’Hearn, DJ, Neubauer, DN, Nieto, FJ, Schwartz, AR, Smith, PL. “Modeling hypersomnolence in sleep-disordered breathing: a novel approach using survival analysis.”. Am J Respir Crit Care Med. vol. 159. 1999. pp. 1703-1709. (These investigators examined clinical and polysomnographic variables and their associations with hypersomnolence as measured by mean sleep latency on an MSLT. In 741 patients with OSA (AHI of at least ten per hour), AHI, the degree of nocturnal hypoxemia, and a measure of sleep fragmentation were independent predictors of this objective measure of hypersomnolence.)
Weaver, TE. “Outcome measurement in sleep medicine practice and research. Part 1: assessment of symptoms, subjective and objective daytime sleepiness, health-related quality of life and functional status”. Sleep Med Rev. vol. 5. 2001. pp. 103-128. (An excellent review of the strengths and weaknesses of the various measurement techniques that have been used to quantify symptoms in patients with OSA.)
Abrishami, A, Khajehdehi, A, Chung, F. “A systematic review of screening questionnaires for obstructive sleep apnea”. Can J Anesth. vol. 57. 2010. pp. 423-438. (A variety of questionnaires have seen widespread use in attempting to estimate a pre-test probability of any given patient's being diagnosed with OSA after definitive sleep testing. The authors performed a systematic review of the most common instruments to assess the quality of their underlying methodologies and their reported predictive values.)
Brown, LK. “Hypoventilation syndromes”. Clin Chest Med. vol. 31. 2010. pp. 249-270. (A comprehensive review of the various hypoventilation syndromes with an extensive discussion on the current state of our knowledge of obesity hypoventilation syndrome.)
Iber, C, Ancoli-Israel, S, Chesson, A, Quan, SF. “The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications”. 2007. (This and the next four publications, sponsored by the American Academy of Sleep Medicine, contain definitive recommendations on various aspects of the diagnosis and treatment of OSA. The recommendations are based on systematic reviews that include assessments of the quality of underlying studies and grading of the strengths of the resulting recommendations.)
Collop, NA, Anderson, WM, Boehlecke, B, Claman, D, Goldberg, R, Gottlieb, DJ. “Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients.”. J Clin Sleep Med. vol. 3. 2007. pp. 737-47.
Kushida, CA, Chediak, A, Berry, RB, Brown, LK, Gozal, D, Iber, C. “Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea.”. J Clin Sleep Med. vol. 4. 2008. pp. 157-71.
Kushida, CA, Morgenthaler, TI, Littner, MR, Alessi, CA, Bailey, D, Coleman, J. “Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances: An update for 2005.”. Sleep. vol. 29. 2006. pp. 240-3.
Aurora, RN, Casey, KR, Kristo, D. “Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults.”. Sleep. vol. 33. 2010. pp. 1408-13.
Pack, AI, Gislason, T. “Obstructive sleep apnea and cardiovascular disease: a perspective and future directions”. Prog Cardiovasc Dis. vol. 51. 2009. pp. 434-51. (A thorough review of known and postulated mechanisms by which OSA acts as a risk factor for cardiovascular disease. Analyzes animal and human data, presents a putative scheme for causality, and discusses the need for and ethical basis of randomized controlled trials in this area.)
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- What every physician needs to know:
- Are you sure your patient has obstructive sleep apnea? What should you expect to find?
- Beware: there are other diseases that can mimic obstructive sleep apnea:
- How and/or why did the patient develop obstructive sleep apnea?
- Which individuals are at greatest risk of developing obstructive sleep apnea?
- What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?
- What imaging studies will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
- What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
- What diagnostic procedures will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
- What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of obstructive sleep apnea?
- If you decide the patient has obstructive sleep apnea, how should the patient be managed?
- What is the prognosis for patients managed in the recommended ways?
- What other considerations exist for patients with obstructive sleep apnea?
- What’s the evidence?