Humans spend almost 30% of their lives sleeping. Since the 1970s, physicians have begun to recognize many of the detrimental consequences of sleep disturbances produced by abnormal breathing patterns, termed sleep-disordered breathing (SDB). ¹ Sleep apnea and other sleep-related breathing disorders constitute the greatest number of sleep disorders seen by pulmonologists and general practitioners in the outpatient setting. SDB has been associated with considerable morbidity.

SDB comprises a wide spectrum of sleep-related breathing abnormalities; those related to increased upper airway resistance include snoring, upper airway resistance syndrome (UARS), and obstructive sleep apnea–hypopnea syndrome (OSAHS). ² Many clinicians regard SDB as a spectrum of diseases. ³ This concept suggests that a person who snores may be exhibiting the first manifestation of SDB and that snoring should not be viewed as normal. A patient can move gradually through the continuum, for example, with weight gain and eventual development of pickwickian syndrome or with alcohol or sedative use, which can cause a person who snores to turn into a snorer with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) can be effective in treating apnea, but the patient may be left with continued residual UARS or snoring. ⁴ Therefore, the clinician must recognize the continuum state of this disease entity because patients can continue to suffer from symptoms caused by one aspect of SDB while being treated for another aspect of SDB.

Snoring

Snoring is one of the most common aspects of SDB and has been described throughout history. In the past, snoring generally had been considered a social nuisance without no consequences for the snorer, only for the suffering bed partner. After sleep apnea syndrome was recognized, snoring began being viewed as an important clinical symptom. Although it is by far the most common symptom of sleep apnea and is usually the main reason for a patient visit, not all patients who snore have sleep apnea.

Definition

Although the definition of snoring may differ depending on the “ear of the beholder,” it is defined by the Random House Dictionary of the English Language as “breathing during sleep with hoarse or harsh sounds as caused by the vibrating of the soft palate.” ⁵ The International Classification of Sleep Disorders: Diagnostic and Coding Manual defines primary snoring (ICSD 786.09) as “loud upper airway breathing sounds in sleep, without episodes of apnea or hypoventilation.” ⁶

Prevalence

It is clearly recognized that snoring is common in the general population, but estimates vary widely of its prevalence in different populations. These differences mainly are due to subjective perception, depending on who is reporting the snoring (the snorer or the bed partner) and how the question is asked by the clinician. Overall, snoring is reported to affect 19% to 37% of the general population and more than 50% of middle-aged men. ⁷ Male predominance has been noted in all snoring epidemiologic studies, possibly due to the differences in perception of snoring by men and women. Other possible reasons for increased male predominance include differences in pharyngeal anatomy and function, hormonal differences and their effects on upper airway muscles, and differences in body fat distribution.

Pathophysiology

Snoring is a result of the changes in the configuration and properties of the upper airway (from the nasopharynx to the laryngopharynx) that occurs during sleep. This sound can be produced by any membranous portion of the airway that lacks cartilaginous support, including the soft palate, uvula, and the pharyngeal walls. Snoring is usually an inspiratory sound, but it can also occur in expiration. ⁸ Snoring can occur during any stage of sleep but is more common during stages 2, 3, and 4. This is because airway elastance and muscle tone due to sympathetic activity and neural output to the upper airway walls are different during rapid eye movement (REM) and non-REM sleep. Multiple predisposing factors can lead to a snoring abnormality, including age (middle or advanced), regional obesity, body posture, use of alcohol and muscle relaxants, retrognathia, nasal blockage, and smoking. ⁹

Signs and Symptoms

A primary snorer is usually asymptomatic and does not suffer from cardiovascular disease. Snoring in this population is usually an annoyance to the bed partner, and the snorer might deny any symptoms of daytime somnolence or difficulty with concentration. In contrast, snoring also can occur in conjunction with a disordered sleep pattern and may be associated with a range of symptoms, including overt OSAHS.

Bed partners, family members, or friends who have shared a room with the sleeping patient initially might complain of loud or disruptive noises. Patients sometimes complain of snoring themselves, a feeling of tiredness on waking, excessive sleepiness during the day, poor work performance, and difficulty with concentration.

Diagnosis

A complete history and careful physical examination are paramount in assessing whether sleep apnea is present in a patient with snoring symptoms. The history and examination results also guide the clinician in deciding whether a nocturnal polysomnogram is necessary and in determining appropriate treatment.

The history should be obtained in the presence of the bed partner, who usually initiates the visit, because the snorer often is unaware of snoring. The clinician also should assess the degree of social disruption caused by the snoring. He or she should ask the bed partner the number of years' duration of the snoring, frequency of snoring (every night or intermittent), postural dependence (lying on side or back), and the association of posture with cessation of breathing.

The patient's risk factors should be assessed, including male gender, increase in weight, ingestion of alcohol, allergies, nasal obstruction, trauma, use of muscle-relaxing medications, and smoking. An assessment of daytime functioning, including concentration levels, work performance, and sleepiness, should be documented. The Epworth Sleepiness Scale (Table 1 ), which assesses the level of daytime sleepiness, has been used to distinguish primary snoring from OSAHS. ¹⁰ A history should be sought of previous surgery or trauma to the upper airways (any site between the nose and the larynx) because the compliance of the airways may be affected. A family predisposition to snoring has been described, and many snorers admit to other family members of having a history of snoring if asked. ¹¹

Laboratory tests for hypothyroidism or acromegaly are indicated only if clinical signs suggest the presence of these disorders. The decision to order other laboratory investigations should be based on the possible medical consequences of the patient's snoring, the probability that apnea is present, and factors that can influence successful treatment.

The two main studies usually used to evaluate snoring are nocturnal polysomnography and an airway assessment. In a position statement, the American College of Chest Physicians and the Association of Sleep Disorders Centers have declared that only snorers suspected of having sleep apnea syndrome should undergo poly-somnography. ¹² The American Thoracic Society has declared in its position statement that snoring alone is not an indication for a sleep study. ¹³

In symptomatic snorers with daytime somnolence, reduced performance, reduced attention, and tiredness, a full nocturnal polysomnogram is needed to establish a diagnosis of sleep apnea or UARS. Nocturnal polysomnography with a recording of sleep architecture and arousals is necessary.

Polysomnography remains the gold standard for diagnosing SDB. A complete polysomnography is often termed a full sleep study. Sleep is recorded from a number of electrophysiologic signals as well as from breathing and limb movement electrodes. This includes an electroencephalogram (EEG) with two leads, electromyography, electro-oculography, respiratory signals from airflow measurements from nasal pressure, nasal temperature, expired carbon dioxide, ventilation from thoracoabdominal movements or nasal pressure, oxygenation levels, and possibly esophageal balloon pressures. Other signals include an electrocardiogram tracing during sleep, pulse rate, position, esophageal pH, and video recording. A detailed airway assessment of upper airway volume and area is not done routinely because it does not predict successful surgical outcomes in a nonapneic snorer. If surgery is being considered, further radiographic imaging can provide an airway assessment and may include cephalometric measurements, computed tomography, or magnetic resonance imaging.

Treatment

Because snoring and sleep apnea are contained within a spectrum of disease states, the treatment of snoring and sleep apnea can overlap. Treatment of snoring should be directed at improving sleep apnea or UARS. In the snorer without sleep apnea or in the primary snorer, initiation of treatment can improve quality of life. Lifestyle modification should be addressed in all patients who snore, including reduction of risk factors such as obesity, alcohol consumption, and use of muscle relaxants.

Noninvasive treatments should be recommended initially, including nasal dilators, tongue-retaining devices, and mandibular advancement appliances that can be fixed or adjusted. Used to treat apneic snorers, tongue-retaining devices hold the tongue in a forward position by applying negative pressure. Subsequently, obstruction at the base of the tongue is relieved and nasal breathing is promoted. In 1995, the Task Force for the Standards of Practice Committee of the American Sleep Disorders Association recommended offering oral appliances to all nonapneic snorers. ¹⁴

Nonsurgical methods such as treating coexisting allergies or nasal congestion, reducing weight, changing sleeping positions, and using ear plugs have met with limited success. Although many of these modalities are anecdotally successful, their efficacy has not been demonstrated in a randomized controlled setting. ¹⁵

Patients should be counseled that CPAP carries the greatest guarantee that snoring will be abolished. Application of nasal CPAP via a nasal mask has significantly altered the medical treatment of sleep apnea, because CPAP can almost completely eliminate snoring. Most nonapneic snorers are reluctant to commit to nasal CPAP, and compliance can become an issue that leads to limited efficacy in this population.

Surgical approaches should be discussed only with patients who suffer from obvious anatomic abnormalities, including nasal or pharyngeal obstruction. Discussions in conjunction with a surgical team should focus on improvement of symptoms; patients should not expect complete resolution of snoring through surgical techniques. Nasal surgery for the relief of nasal obstruction due to septal deviation or polyps may be associated with improvement in snoring in up to 75% of patients. ¹⁶ It is believed that nasal surgery alone is unlikely to cure snoring, but it can improve breathing, allowing patients to better tolerate therapies such as nasal CPAP. Uvulopalatopharyngoplasty (UPPP) (Fig. 1) and laser-assisted palatal surgery each have reported success rates of greater than 70% for primary snoring. ¹⁷

Laser-assisted uvulopalatoplasty (LAUP) is similar to conventional UPPP but is performed in an outpatient setting under local anesthesia. Less adjacent palatal tissue is resected and only partial uvulectomy is performed. LAUP is a sequential procedure that usually takes three or four outpatient visits to complete. ¹⁸

Outcomes

The best ways to assess snoring treatment outcomes are through the subjective method (by asking the bed partner or the snorer about the effects of therapy) and through the objective method, which is also problematic because no standardized measurement techniques and data analysis protocols exist. With these limitations, it is more appropriate to assess treatment outcomes subjectively using a well-designed questionnaire answered by the person who can best assess the state of snoring before and after the intervention.

Back to Top

Upper airway resistance syndrome

UARS can cause symptoms similar to those found in OSA, yet this syndrome is considerably different due to the lack of oxygen desaturation found during sleep studies. Upper airway resistance syndrome was a term first applied to patients who were found to have excessive daytime sleepiness without a clear cause on a multiple sleep latency test, which was further documented by an overnight polysomnogram. These patients were often said to have idiopathic hypersomnia. After many of these patients were further tested with invasive polysomnography (including an esophageal balloon transducer and full pneumotachograph), they were found to have increased upper airway resistance. Resistance was indicated by increased negative esophageal inspiratory pressure. ²

Definition

UARS is characterized by repeated arousals, due to upper airway resistance, that lead to excessive daytime sleepiness. This disorder often produces a snoring pattern termed crescendo snoring. When the crescendo snoring episode ends, an arousal occurs with rapid decrease in upper airway resistance; the snoring then disappears and stops for a period. UARS events are noted to be typically short: one to three breaths in duration. These events have been termed respiratory effort-related arousals (RERAs). In UARS, unlike in OSAHS, there is no evidence of oxygen desaturation. ² For the measurement criteria to be classified as a RERA, there must be a pattern of progressively increased negative esophageal pressure that is terminated by a sudden change in the pressure to a less-negative level and a sleep arousal. Furthermore, the event must last 10 seconds or longer.

Prevalence

The prevalence of UARS in the general adult population is unknown, yet it has been estimated to be as high as 10% to 15% when the definition is applied to adults who suffer from snoring and excessive daytime sleepiness. ¹⁹ It has been suggested that UARS occurs in a less-obese younger population and more commonly in women than does OSAHS. ²

Pathophysiology

Guilleminault and coworkers ²⁰ demonstrated that many nonapneic patients show a reduction in cross-sectional area of the pharynx during sleep. Reduction in airway area is sufficient to avoid hypopneas and apnea but enough to increase upper airway resistance. Patients with UARS suffer from increased airway resistance, which generates snoring and then leads to arousal episodes and ultimately to excessive daytime sleepiness.

Signs and Symptoms

Although patients with UARS share no standard clinical presentation, the cardinal symptom of UARS is excessive daytime sleepiness or fatigue. Some patients also complain of difficulty with concentration, morning headaches, impotence, difficulty sleeping, or restless sleep. They often report having repetitive nightmares, such as choking or being buried alive, which can suggest difficulty with breathing. Again, snoring is not a necessary feature of this syndrome because the upper airway resistance is due to a partial decrease in airway cross-sectional area; therefore, the airway walls do not have to vibrate and produce a snoring sound. ³

Diagnosis

UARS should not be overdiagnosed. Three essential clinical features consistently have been used by investigators and authors to diagnose UARS: excessive daytime somnolence; an elevated EEG arousal index, with the arousal related to increased respiratory efforts; and a normal respiratory disturbance index (RDI) of less than five events per hour of sleep. ²¹

UARS is present only if there are documented elevations in upper airway resistance, sleep fragmentation, and daytime dysfunction or excessive daytime sleepiness. The clinical complaint of fatigue or daytime sleepiness can be documented by an abnormal increase in the Epworth Sleepiness Scale (see Table 1 ) score to a value greater than 10 or by use of another validated sleep questionnaire. A low RDI is also needed to distinguish UARS from OSAHS. The elevated EEG arousal index related to increased respiratory efforts is the specific measurement that distinguishes UARS from idiopathic hypersomnolence. ²² The clinical complaint of snoring (including crescendo snoring), increase in snoring intensity before EEG arousals, and clinical improvement with a short-term trial of nasal CPAP can be regarded as supporting a diagnosis of UARS.

The diagnosis of UARS requires full polysomnography. Although measurements of upper airway resistance were first used, based on the original definition of UARS, substitute measurements of effort and ventilation may be used as long as there is no evidence of hypopneas or apneas. A normal apnea-hypopnea index (AHI) of less than five events per hour of sleep should be seen on the polysomnograph. Additionally, EEG arousals should occur at a rate of more than 10 per hour of sleep and must be associated with increased respiratory effort (usually made by nocturnal esophageal pressure monitoring).

Current literature supports that esophageal pressures greater than −10 cm H₂O are abnormal. The measurement of esophageal pressure is the gold standard for measuring respiratory effort and is the only consistent measurement reported for the diagnosis of UARS. Substitute measurements can include inductive plethysmography, strain gauges, oronasal temperature measurements, nasal pressures, and the carbon monoxide levels in exhaled gas. Arousals are documented from the EEG tracings and electromyography, although changes in heart rate, ventilation, and other measurements of autonomic activity may play some role in the future. ³

Treatment

CPAP, surgery, oral appliances, and weight loss are possible treatment options for UARS. Ideally, the recommended treatment of UARS should be effective, relieve symptoms, and produce normalized studies after therapy. These therapies also should be covered by health insurance and have long-term effectiveness. Thus far, however, none of the proposed treatments has fully met these criteria.

Outcomes

Data in the sleep literature are not clear-cut regarding the efficacy, safety, and compliance of UARS treatment modalities, including weight loss, nasal CPAP, oral appliances, and surgery.

Back to Top

Obstructive sleep apnea-hypopnea syndrome

OSAHS is not a new clinical entity but is one that has been recognized only recently. Evolving from the historical accounts of sleep apnea to the present day, the most significant development in the diagnosis of sleep-disordered breathing is the publication of the American Academy of Sleep Medicine's report on recommendations for syndrome definition and measurement techniques in clinical research. Within this report, the older term obstructive sleep apnea was appropriately changed to the newer term obstructive sleep apnea-hypopnea syndrome. ²² The complications and potential consequences of OSAHS include increased risks of hypertension and cardiovascular events as well as cerebrovascular events. OSAHS affects not only the health of the sufferer but also the bed partner's sleep state. ²³

Definition

OSAHS is characterized by recurrent episodes of partial or complete airway obstruction during sleep due to repetitive collapse of the pharynx, necessitating recurrent awakenings or arousals to re-establish airway patency. This airway obstruction or partial obstruction manifests in a reduction in airflow, termed hypopnea, or in a complete cessation of airflow, termed apnea, despite ongoing inspiratory effort. Hypopnea is defined in adults as a 10-second event during which there is continued breathing but in which ventilation during sleep is reduced by at least 50% from baseline. Apnea is total cessation of airflow for at least 10 seconds. Apnea can be obstructive or central. Obstructive apnea is defined as cessation of airflow but with continued respiratory effort, whereas central apnea is a state in which airflow and respiratory effort are both absent. Apnea also can be both central and obstructive, although obstructive apnea is more common. Hypopnea can produce clinical sequelae similar to those of apnea, but in general, apnea may be associated with a greater fall in oxygen saturations.

For sleep-disordered breathing to be diagnosed as OSAHS, the patient must have at least five obstructed breathing events per hour (or 30 events per 6 hours of sleep). These events can be a combination of OSA, hypopnea, or respiratory effort-related arousals. The patient must also have either excessive daytime sleepiness or at least two of choking or gasping from sleep, recurrent awakenings from sleep, feeling unrefreshed after sleep, daytime fatigue, or poor concentration. This second group of signs and symptoms must not be better explained by other factors. ²

The RDI (or AHI) is the number of apneas plus hypopneas per hour of sleep. This index has now become the standard by which to define and quantify the severity of OSAHS. An RDI of greater than 15 events per hour indicates possible OSAHS. Generally, as the RDI increases, the severity of apnea increases.

Prevalence

Most apnea studies have indicated that OSAHS is a relatively common disorder. In a large U.S. epidemiologic study in subjects ages 30 to 60 years, 24% of men and 9% of women had abnormal AHI indices. ² Overall, it has been estimated that more than 158 million adults ages 25 years and older suffer from sleep apnea and that more than 10 million men and women currently go untreated for the disorder in the United States. Currently, the prevalence of OSAHS is conservatively estimated to be 1% to 2% in middle-aged men and one half that, or approximately 0.5% to 1%, in middle-aged women. ²⁴ It is estimated that only 1% of OSAHS patients are receiving appropriate treatment for their disease. ²⁵

Pathophysiology

OSAHS occurs due to a narrowing of the upper airway during sleep. The site of the narrowing is usually at the level of the pharynx. ²⁶ Airway occlusion is noted to be limited to inspiration, which exerts negative pharyngeal pressure and reduces the tone of the genioglossus muscle. This theory remains the cornerstone of understanding OSAHS.

Upper airway size in OSAHS patients is smaller than in normal subjects, as assessed by CT scan and resistance measurements. Patients with OSAHS also have been noted to have a more elliptical upper airway shape than normal subjects, but this may be due to increased body mass as well. The difference in airway size in OSAHS patients is due to fat deposition and facial bone structure. Obese patients with OSAHS have fat deposits lateral to the pharynx. Although this fat deposit might not be substantial, it can predispose patients to OSAHS. ²⁷ Retroposition of the maxilla and mandible predisposes patients to OSAHS due to a narrowing of the pharynx caused by posterior displacement of the tongue and palate. These facial traits also are more common in families with OSAHS. ²⁸ Patients with OSAHS also have increased palatal muscle bulk, which usually responds to positive pressure.

Genetics might play an important role in the pathophysiology of OSAHS. The disorder is more common among family members suffering from OSAHS than in the general population. This relation seems to be independent of familial obesity tendencies. ⁸

Signs and Symptoms

The dominant symptoms of OSAHS are sleepiness and daytime somnolence. Other symptoms include difficulty with concentration, fatigue, unrefreshing sleep, nocturnal choking, nocturia, depression, and decreased libido. Bed partners might report snoring, apneas, restless sleep, or irritability. In investigating sleepiness, note whether the patient falls asleep frequently against his or her will or in a dangerous situation, such as when driving.

Although there is no gold standard definition for sleepiness, the Epworth Sleepiness Scale can assist the clinician in documenting this symptom. A score of greater than 12 of 24 points on the Epworth scale is defined as abnormally sleepy (see Table 1 ). Morning headache was initially reported as a feature of OSAHS, but its true association is debatable. ²⁹ Patients should also be asked about weight gain and the relation of developing symptoms to any gain in weight.

Although physical examination has not proved helpful in identifying patients with SDB, BMI and neck circumference (indicators of obesity) appear to be good clinical predictors for OSAHS. BMI (weight in kg/height in meters) is the most commonly used clinical predictor for OSAHS. Obesity is defined as a BMI greater than 30 kg/m². Upper body obesity also may be associated with a higher risk for OSAHS.

Physical findings of OSAHS can include obesity, increased neck circumference, crowding of the upper airway, macroglossia, enlarged tonsils, nasal obstruction, retrognathia, hypertension, lower limb edema, and signs of cor pulmonale. Laboratory investigations can include secondary polycythemia, proteinuria respiratory failure, nocturnal cardiac arrhythmia, and gastroesophageal reflux disease.

Diagnosis

Because many of the symptoms of OSA are nonspecific, the index of clinical suspicion for OSAHS needs to be high to make the diagnosis. The differential diagnosis for OSAHS should include primary snoring, chronic hypoventilation syndrome, and central sleep apnea and Cheyne-Stokes respiration.

Patients suspected to have OSAHS should undergo polysomnography. Because night-to-night variability can occur in mild cases of the disorder, misdiagnosis can occur. Therefore, a negative first-night test is insufficient to rule out OSAHS in patients in whom there is a high clinical suspicion of the disease.

Many other types of sleep studies are available, with varying settings and parameters measured. A complete level I study is performed in the laboratory; partial and limited studies can be conducted in the home. However, the American Sleep Disorders Association advises that standard polysomnography is the accepted test for diagnosing and determining the severity and treatment of OSA. The association recommends that portable or unattended recordings are an acceptable alternative only when clinical symptoms are severe and indicate sleep apnea, initiation of treatment is urgent and a standard polysomnography is not readily available, the patient cannot be studied in a sleep laboratory, or follow-up studies are needed to evaluate therapy response.

Treatment

Adequate treatment of OSAHS results in improvement of symptoms and can alter morbidity and mortality outcomes. Current therapies in the treatment of sleep apnea are aimed at widening the pharyngeal airway, making it less apt to collapse, or at pneumatically splinting the airway open using CPAP. CPAP is very effective in eliminating pharyngeal collapse, improving overall symptoms, and reducing cardiovascular sequelae, making it the treatment of choice for OSAHS.

Bilevel positive airway pressure (BiPAP) allows the clinician to set different pressures for inspiratory and expiratory breaths. This may be beneficial for patients who occasionally complain of feeling excessive air pressure or of having the sensation of exhaling against positive pressure. The routine use of BiPAP has not been shown to increase compliance, but in patients who have high CPAP requirements, BiPAP may be a more comfortable option.

Oral appliances can enlarge the pharyngeal airway during sleep by moving either the tongue or the mandible anteriorly, partially relieving apnea. Such appliances are probably more useful in patients with mild apnea than in those with severe apnea.

Upper airway surgery, including radiofrequency ablation of the tongue or soft palate (somnoplasty), LAUP, UPPP, or genioglossal advancement with hypoid myotomy, bimaxillary advancement, or maxillomandibular advancement, aims to enlarge the pharyngeal space and prevent airway collapse. Success rates range from 30% for the less aggressive interventions to 90% for the more aggressive procedures. Common side effects include pain, alteration in taste, and nasal regurgitation.

The role of pharmacotherapy for sleep apnea remains controversial. Experimental evidence suggests that serotoninergics at certain doses improve sleep efficiency; however, sufficient data are not available to support their routine use.

Outcomes

OSAHS outcomes, including feelings of vitality, energy, and mental summary scores, all improve with treatment. Significant study data have accumulated demonstrating reductions in cardiovascular morbidity and mortality with CPAP therapy for OSAHS. In fact, health care use is significantly reduced when patients adhere to CPAP therapy, resulting in fewer physician claims and hospital stays.

Summary

• Sleep-disordered breathing refers to a wide spectrum of sleep-related breathing abnormalities; those related to increased upper airway resistance include snoring, upper airway resistance syndrome, and obstructive sleep apnea-hypopnea syndrome.
• Polysomnography remains the gold standard for diagnosing sleep-disordered breathing.
• Lifestyle modifications should be addressed in all patients suffering from snoring, including reduction of risk factors such as obesity and use of alcohol and muscle relaxants.
• Patients should be counseled that continuous positive airway pressure carries the greatest assurance that snoring will be abolished.
• Surgical approaches should be discussed with only a limited number of patients, mainly those who suffer from obvious anatomic abnormalities

Back to Top

Suggested Readings

• International Classification of Sleep Disorders, revised: Diagnostic and Coding Manual. 2001; ;Chicago. 195.
• Risk factors in a general population for snoring. Importance of cigarette smoking and obesity. Chest. 93: 1988; 678-683.
• Snoring and sleep disordered breathing. Lee-Chiong T, Sateia M , Carskadon M. Sleep Medicine. 2002; ;Philadelphia. 349-355.
• Theory and measurements of snores. J Appl Physiol. 74: 1993; 2828-2837.
• Some epidemiological data on snoring and cardiocirculatory disturbances. Sleep. 3: 1980; 221-224.
• Snoring: Pathogenic, clinical, and therapeutic aspects. Kryger M, Roth T , Dement W. Principles and Practice of Sleep Medicine. 2nd ed 1994; ;Philadelphia. 621-629.
• American Thoracic Society Consensus Conference on indications and standards for cardiopulmonary sleep studies. Am Rev Respir Dis. 139: 1989; 559-568.
• The Random House Dictionary of the English Language. 2001; ;New York.
• Sleep apnea syndromes. Fishman AP. Fishman's Pulmonary Diseases and Disorders. 3rd ed 1998; ;New York. 1617-1646.
• The impact of sleep disordered breathing on other diseases. Presented at 98th International Conference of the American Thoracic Society, Atlanta, May 17-22, 2002. Available at www.medscape.com/viewarticle/437261 (accessed January 14, 2008)