- Obstructive sleep apnea
Obstructive sleep apnea Classification and external resources
Obstructive sleep apnea
ICD-10 G47.3 ICD-9 327.23 eMedicine ped/2114 MeSH D012891
Obstructive sleep apnea (OSA) or obstructive sleep apnea syndrome is the most common type of sleep apnea and is caused by obstruction of the upper airway. It is characterized by repetitive pauses in breathing during sleep, despite the effort to breathe, and is usually associated with a reduction in blood oxygen saturation. These pauses in breathing, called apneas (literally, "without breath"), typically last 20 to 40 seconds.
The individual with OSA is rarely aware of having difficulty breathing, even upon awakening. It is recognized as a problem by others witnessing the individual during episodes or is suspected because of its effects on the body (sequelae). OSA is commonly accompanied with snoring.
Symptoms may be present for years, even decades without identification, during which time the sufferer may become conditioned to the daytime sleepiness and fatigue associated with significant levels of sleep disturbance. Persons who sleep alone without a long-term human partner may not be told about their sleep disorder symptoms.
Since the muscle tone of the body ordinarily relaxes during sleep, and since, at the level of the throat, the human airway is composed of walls of soft tissue, which can collapse, it is easy to understand how breathing can be obstructed during sleep. Although a very minor degree of OSA is considered to be within the bounds of normal sleep, and many individuals experience episodes of OSA at some point in life, a much smaller percentage of people are afflicted with chronic, severe OSA.
Many people experience episodes of OSA for only a short period of time. This can be the result of an upper respiratory infection that causes nasal congestion, along with swelling of the throat, or tonsillitis that temporarily produces very enlarged tonsils. The Epstein-Barr virus, for example, is known to be able to dramatically increase the size of lymphoid tissue during acute infection, and OSA is fairly common in acute cases of severe infectious mononucleosis. Temporary spells of OSA syndrome may also occur in individuals who are under the influence of a drug (such as alcohol) that may relax their body tone excessively and interfere with normal arousal from sleep mechanisms.
- 1 Signs and symptoms
- 2 Risk factors
- 3 Epidemiology
- 4 Causes
- 5 Pathophysiology
- 6 Diagnosis
- 7 Treatment
- 8 Prognosis
- 9 See also
- 10 References
- 11 External links
Signs and symptoms
Common signs of OSA include unexplained daytime sleepiness, restless sleep, and loud snoring (with periods of silence followed by gasps). Less common symptoms are morning headaches; insomnia; trouble concentrating; mood changes such as irritability, anxiety and depression; forgetfulness; increased heart rate and/or blood pressure; decreased sex drive; unexplained weight gain; increased urination and/or nocturia; frequent heartburn or gastroesophageal reflux disease; and heavy night sweats.
In adults, the most typical individual with OSA syndrome suffers from obesity, with particular heaviness at the face and neck. Obesity is not always present with OSA; in fact, a significant number of adults with normal body mass indices (BMIs) have decrease in muscle tone causing airway collapse and sleep apnea. The cause of this decreased tone is not presently understood. The hallmark symptom of OSA syndrome in adults is excessive daytime sleepiness. Typically, an adult or adolescent with severe long-standing OSA will fall asleep for very brief periods in the course of usual daytime activities if given any opportunity to sit or rest. This behavior may be quite dramatic, sometimes occurring during conversations with others at social gatherings.
The hypoxia (absence of oxygen supply) related to OSA may cause changes in the neurons of the hippocampus and the right frontal cortex. Research using neuro-imaging revealed evidence of hippocampal atrophy in people suffering from OSA. They found that some sufferers have problems in mentally manipulating non-verbal information and in executive function.
Although this so called "hypersomnolence" (excessive sleepiness) may also occur in children, it is not at all typical of young children with sleep apnea. Toddlers and young children with severe OSA instead ordinarily behave as if "over-tired" or "hyperactive." Adults and children with very severe OSA also differ in typical body habitus. Adults are generally heavy, with particularly short and heavy necks. Young children, on the other hand, are generally not only thin, but may have "failure to thrive", where growth is reduced. Poor growth occurs for two reasons: the work of breathing is intense enough that calories are burned at high rates even at rest, and the nose and throat are so obstructed that eating is both tasteless and physically uncomfortable. OSA in children, unlike adults, is often caused by obstructive tonsils and adenoids and may sometimes be cured with tonsillectomy and adenoidectomy.
This problem can also be caused by excessive weight in children. In this case, the symptoms are more like the symptoms adults feel: restlessness, exhaustion, etc.
Children with OSA may experience learning and memory deficits and OSA has also been linked to lowered childhood IQ scores.
Old age is often accompanied by muscular and neurological loss of muscle tone of the upper airway. Decreased muscle tone is also temporarily caused by chemical depressants; alcoholic drinks and sedative medications being the most common. Permanent premature muscular tonal loss in the upper airway may be precipitated by traumatic brain injury, neuromuscular disorders, or poor adherence to chemical and or speech-therapy treatments.
Individuals with decreased muscle tone, increased soft tissue around the airway, and structural features that give rise to a narrowed airway are at high risk for OSA. Men, in which the anatomy is typified by increased mass in the torso and neck, are at increased risk of developing sleep apnea, especially through middle age and later. Women suffer typically less frequently and to a lesser degree than do men, owing partially to physiology, but possibly also to differential levels of progesterone. Prevalence in post-menopausal women approaches that of men in the same age range. Women are at greater risk for developing OSA during pregnancy.
OSA also appears to have a genetic component; those with a family history of it are more likely to develop it themselves. Lifestyle factors such as smoking may also increase the chances of developing OSA as the chemical irritants in smoke tend to inflame the soft tissue of the upper airway and promote fluid retention, both of which can result in narrowing of the upper airway. An individual may also experience or exacerbate OSA with the consumption of alcohol, sedatives, or any other medication that increases sleepiness as most of these drugs are also muscle relaxants.
OSA is more frequent than central sleep apnea and is the most common category of sleep-disordered breathing. It is a common condition in many parts of the world.
If studied carefully in a sleep lab by polysomnography (formal "sleep study"), it is believed by some authorities that approximately 1 in 5 American adults would have at least mild OSA. The precise prevalence of OSA among the adult population in western Europe and North America, however, has not been confidently established. In the mid-1990s it was estimated to be 3-4% of women and 6-7% of men.
Most cases of OSA are believed to be caused by:
- old age (natural or premature),
- brain injury (temporary or permanent),
- decreased muscle tone,
- increased soft tissue around the airway (sometimes due to obesity), and
- structural features that give rise to a narrowed airway.
Decreased muscle tone can be caused by drugs or alcohol, or it can be caused by neurological problems or other disorders. Some people have more than one of these issues. There is also a theory that long-term snoring might induce local nerve lesions in the pharynx in the same way as long-term exposure to vibration might cause nerve lesions in other parts of the body. Snoring is a vibration of the soft tissues of the upper airways, and studies have shown electrophysiological findings in the nerves and muscles of the pharynx indicating local nerve lesions.
There are patterns of unusual facial features that occur in recognizable syndromes. Some of these craniofacial syndromes are genetic, others are from unknown causes. In many craniofacial syndromes, the features that are unusual involve the nose, mouth and jaw, or resting muscle tone, and put the individual at risk for OSA syndrome.
Down Syndrome is one such syndrome. In this chromosomal abnormality, several features combine to make the presence of obstructive sleep apnea more likely. The specific features in Down Syndrome that predispose to obstructive sleep apnea include: relatively low muscle tone, narrow nasopharynx, and large tongue. Obesity and enlarged tonsils and adenoids, conditions that occur commonly in the western population, are much more likely to be obstructive in a person with these features than without them. Obstructive sleep apnea does occur even more frequently in people with Down Syndrome than in the general population. A little over 50% of all people with Down Syndrome suffer from obstructive sleep apnea (de Miguel-Díez, et al. 2003), and some physicians advocate routine testing of this group (Shott, et al. 2006).
In other craniofacial syndromes, the abnormal feature may actually improve the airway, but its correction may put the person at risk for obstructive sleep apnea after surgery, when it is modified. Cleft palate syndromes are such an example. During the newborn period, all humans are obligate nasal breathers. The palate is both the roof of the mouth and the floor of the nose. Having an open palate may make feeding difficult, but generally does not interfere with breathing, in fact - if the nose is very obstructed an open palate may relieve breathing. There are a number of clefting syndromes in which the open palate is not the only abnormal feature, additionally there is a narrow nasal passage - which may not be obvious. In such individuals, closure of the cleft palate- whether by surgery or by a temporary oral appliance, can cause the onset of obstruction.
Skeletal advancement in an effort to physically increase the pharyngeal airspace is often an option for craniofacial patients with upper airway obstruction and small lower jaws (mandibles). These syndromes include Treacher Collins Syndrome and Pierre Robin Sequence. Mandibular advancement surgery is often just one of the modifications needed to improve the airway, others may include reduction of the tongue, tonsillectomy or modified uvulopalatoplasty.
OSA is a also serious post-operative complication that seems to be most frequently associated with pharyngeal flap surgery, compared to other procedures for treatment of velopharyngeal inadequacy (VPI). In OSA, recurrent interruptions of respiration during sleep are associated with temporary airway obstruction. Following pharyngeal flap surgery, depending on size and position, the flap itself may have an "obturator" or obstructive effect within the pharynx during sleep, blocking ports of airflow and hindering effective respiration. There have been documented instances of severe airway obstruction, and reports of post-operative OSA continue to increase as healthcare professionals (i.e. physicians, speech language pathologists) become more educated about this possible dangerous condition. Subsequently, in clinical practice, concerns of OSA have matched or exceeded interest in speech outcomes following pharyngeal flap surgery.
The surgical treatment for velopalatal insufficiency may cause obstructive sleep apnea syndrome. When velopalatal insufficiency is present, air leaks into the nasopharynx even when the soft palate should close off the nose. A simple test for this condition can be made by placing a tiny mirror at the nose, and asking the subject to say "P". This p sound, a plosive, is normally produced with the nasal airway closed off - all air comes out of the pursed lips, none from the nose. If it is impossible to say the sound without fogging a nasal mirror, there is an air leak - reasonable evidence of poor palatal closure. Speech is often unclear due to inability to pronounce certain sounds. One of the surgical treatments for velopalatal insufficiency involves tailoring the tissue from the back of the throat and using it to purposefully cause partial obstruction of the opening of the nasopharynx. This may actually cause OSA syndrome in susceptible individuals, particularly in the days following surgery, when swelling occurs (see below: Special Situation: Anesthesia and Surgery).
The normal sleep/wake cycle in adults is divided into REM (rapid eye movement) sleep, non-REM (NREM) sleep, and consciousness. NREM sleep is further divided into Stages 1, 2 and 3 NREM sleep. The deepest stage (stage 3 of NREM) is required for the physically restorative effects of sleep, and in pre-adolescents this is the period of release of human growth hormone. NREM stage 2 and REM, which combined are 70% of an average person's total sleep time, are more associated with mental recovery and maintenance. During REM sleep in particular, muscle tone of the throat and neck, as well as the vast majority of all skeletal muscles, is almost completely attenuated, allowing the tongue and soft palate/oropharynx to relax, and in the case of sleep apnea, to impede the flow of air to a degree ranging from light snoring to complete collapse. In the cases where airflow is reduced to a degree where blood oxygen levels fall, or the physical exertion to breathe is too great, neurological mechanisms trigger a sudden interruption of sleep, called a neurological arousal. These arousals rarely result in complete awakening, but can have a significant negative effect on the restorative quality of sleep. In significant cases of OSA, one consequence is sleep deprivation due to the repetitive disruption and recovery of sleep activity. This sleep interruption in stage 3 (also called slow-wave sleep), and in REM sleep, can interfere with normal growth patterns, healing, and immune response, especially in children and young adults.
Diagnosis of OSA is often based on a combination of patient history and tests (lab- or home-based). These tests range, in decreasing order of cost, complexity and tethering of the patient (number and type of channels of data recorded), from lab-attended full polysomnography ("sleep study") down to single-channel home recording. In the USA, these categories are associated with insurance classification from Type I down to Type IV. Reimbursement rules vary among European countries.
AHI Rating <5 Normal 5-15 Mild 15-30 Moderate >30 Severe
Polysomnography in diagnosing OSA characterizes the pauses in breathing. As in central apnea, pauses are followed by a relative decrease in blood oxygen and an increase in the blood carbon dioxide. Whereas in central sleep apnea the body's motions of breathing stop, in OSA the chest not only continues to make the movements of inhalation, butt the movements typically become even more pronounced. Monitors for airflow at the nose and mouth demosntrate that efforts to breathe are not only present, but that they are often exaggerated. The chest muscles and diaphragm contract and the entire body may thrash and struggle.
An "event" can be either an apnea, characterised by complete cessation of airflow for at least 10 seconds, or a hypopnea in which airflow decreases by 50 percent for 10 seconds or decreases by 30 percent if there is an associated decrease in the oxygen saturation or an arousal from sleep . To grade the severity of sleep apnea, the number of events per hour is reported as the apnea-hypopnea index (AHI). An AHI of less than 5 is considered normal. An AHI of 5-15 is mild; 15-30 is moderate and more than 30 events per hour characterizes severe sleep apnea.
In patients who are at high likelihood of having OSA, a randomized controlled trial found that home oximetry (a non-invasive method of monitoring blood oxygenation) may be adequate and easier to obtain than formal polysomnography. High probability patients were identified by an Epworth Sleepiness Scale (ESS) score of 10 or greater and a Sleep Apnea Clinical Score (SACS) of 15 or greater. Home oximetry, however, does not measure apneic events or respiratory event-related arousals and thus does not produce an AHI value.
There are a variety of treatments for OSA; use is determined by an individual patient's medical history, the severity of the disorder and, most importantly, the specific cause of the obstruction.
In acute infectious mononucleosis, for example, although the airway may be severely obstructed in the first 2 weeks of the illness, the presence of lymphoid tissue (suddenly enlarged tonsils and adenoids) blocking the throat is usually only temporary. A course of anti-inflammatory steroids such as prednisone (or another kind of glucocorticoid drug) is often given to reduce this lymphoid tissue. Although the effects of the steroids are short term, in most affected individuals, the tonsillar and adenoidal enlargement are also short term, and will be reduced on its own by the time a brief course of steroids is completed. In unusual cases where the enlarged lymphoid tissue persists after resolution of the acute stage of the Epstein-Barr infection, or in which medical treatment with anti-inflammatory steroids does not adequately relieve breathing, tonsillectomy and adenoidectomy may be urgently required.
OSA in children is sometimes due to chronically enlarged tonsils and adenoids. Tonsillectomy and adenoidectomy is curative. The operation may be far from trivial, especially in the worst apnea cases, in which growth is retarded and abnormalities of the right heart may have developed. Even in these extreme cases, the surgery tends to cure not only the apnea and upper airway obstruction, but allows normal subsequent growth and development. Once the high end-expiratory pressures are relieved, the cardiovascular complications reverse themselves. The postoperative period in these children requires special precautions (see "Surgery and obstructive sleep apnea syndrome" below).
The treatment of OSA in adults with poor oropharyngeal airways secondary to heavy upper body type is varied. Unfortunately, in this most common type of OSA, unlike some of the cases discussed above, reliable cures are not the rule.
Some treatments involve lifestyle changes, such as avoiding alcohol and medications that relax the central nervous system (for example, sedatives and muscle relaxants), losing weight, and quitting smoking. Some people are helped by special pillows or devices that keep them from sleeping on their backs, or oral appliances to keep the airway open during sleep. For those cases where these conservative methods are inadequate, doctors can recommend continuous positive airway pressure (CPAP), in which a face mask is attached to a tube and a machine that blows pressurized air into the mask and through the airway to keep it open. There are also surgical procedures intended to remove and tighten tissue and widen the airway, but none has been reproducibly successful. Some individuals may need a combination of therapies to successfully treat their condition.
The most widely used current therapeutic intervention is positive airway pressure whereby a breathing machine pumps a controlled stream of air through a mask worn over the nose, mouth, or both. The additional pressure splints or holds open the relaxed muscles, just as air in a balloon inflates it. There are several variants:
- (CPAP), or continuous positive airway pressure, in which a computer controlled air flow generator, generates an airstream at a constant pressure. This pressure is prescribed by the patient's physician, based on an overnight test or titration. Newer CPAP models are available which slightly reduce pressure upon exhalation to increase patient comfort and compliance. CPAP is the most common treatment for obstructive sleep apnea.
- (VPAP), or variable positive airway pressure, also known as bilevel or BiPAP, uses an electronic circuit to monitor the patient's breathing, and provides two different pressures, a higher one during inhalation and a lower pressure during exhalation. This system is more expensive, and is sometimes used with patients who have other coexisting respiratory problems and/or who find breathing out against an increased pressure to be uncomfortable or disruptive to their sleep.
- (APAP), or automatic positive airway pressure, is the newest form of such treatment. An APAP machine incorporates pressure sensors and a computer which continuously monitors the patient's breathing performance. It adjusts pressure continuously, increasing it when the user is attempting to breathe but cannot, and decreasing it when the pressure is higher than necessary. Although FDA approved, these devices are still considered experimental by many, and are not covered by most insurance plans under a APAP specific code. Auto CPAP machines can be covered at rate of a CPAP machine.
A second type of physical intervention, a Mandibular advancement splint (MAS), is sometimes prescribed for mild or moderate sleep apnea sufferers. The device is a mouthguard similar to those used in sports to protect the teeth. For apnea patients, it is designed to hold the lower jaw slightly down and forward relative to the natural, relaxed position. This position holds the tongue farther away from the back of the airway, and may be enough to relieve apnea or improve breathing for some patients. The FDA accepts only 16 oral appliances for the treatment of sleep apnea. A listing is available at its website.
Oral appliance therapy is less effective than CPAP, but is more 'user friendly'. Side-effects are common, but rarely is the patient aware of them.
There are no effective drug-based treatments for obstructive sleep apnea that have FDA approval. However, a clinical trial of mirtazapine, has shown early promise at the University of Illinois at Chicago. This small, early study found a 50% decrease in occurrence of apnea episodes and 28% decrease in sleep disruptions in 100% of patients (twelve patients) taking them. Nonetheless, due to the risk of weight gain and sedation (two risk factors and consequences of sleep apnea) it is not recommended. An effort to improve the effects of mirtazapine by combining it with another existing medication was cancelled during Phase IIa trials in 2006. Dr. David Carley and Dr. Miodrag Radulovacki, the sleep researchers who were behind the initial clinical trial of mirtazapine are now working on a new treatment that consists of two other existing medications taken off-label together for treatment of sleep apnea.
Oral administration of the methylxanthine theophylline (chemically similar to caffeine) can reduce the number of episodes of apnea, but can also produce side effects such as heart palpitations and insomnia. Theophylline is generally ineffective in adults with OSA, but is sometimes used to treat central sleep apnea (see below), and infants and children with apnea.
When other treatments do not completely treat the OSA, drugs are sometimes prescribed to treat a patient's daytime sleepiness or somnolence. These range from stimulants such as amphetamines to modern anti-narcoleptic medicines. The anti-narcoleptic medicine modafinil is seeing increased use in this role as of 2004[update].
In most cases, weight loss will reduce the number and severity of apnea episodes. In the morbidly obese, a major loss of weight (such as what occurs after bariatric surgery) can sometimes cure the condition.
Some researchers believe that OSA is at root a neurological condition, in which nerves that control the tongue and soft palate fail to sufficiently stimulate those muscles, leading to over-relaxation and airway blockage. A few experiments and trial studies have explored the use of pacemakers and similar devices, programmed to detect breathing effort and deliver gentle electrical stimulation to the muscles of the tongue.
This is not a common mode of treatment for OSA patients as of 2004, but it is an active field of research.
A number of different surgeries are available to improve the size or tone of a patient's airway. For decades, tracheostomy was the only effective treatment for sleep apnea. It is used today only in rare, intractable cases that have withstood other attempts at treatment. Modern operations employ one or more of several options, tailored to each patient's needs. Success rates are directly proportional to the accuracy in the initial diagnosis of the site of obstruction.
- Nasal surgery, including turbinectomy (removal or reduction of a nasal turbinate), or straightening of the nasal septum, in patients with nasal obstruction or congestion which reduces airway pressure and complicates OSA.
- Tonsillectomy and/or adenoidectomy in an attempt to increase the size of the airway.
- Removal or reduction of parts of the soft palate and some or all of the uvula, such as uvulopalatopharyngoplasty (UPPP) or laser-assisted uvulopalatoplasty (LAUP). Modern variants of this procedure sometimes use radiofrequency waves to heat and remove tissue.
- Reduction of the tongue base, either with laser excision or radiofrequency ablation.
- Genioglossus Advancement, in which a small portion of the lower jaw that attaches to the tongue is moved forward, to pull the tongue away from the back of the airway.
- Hyoid Suspension, in which the hyoid bone in the neck, another attachment point for tongue muscles, is pulled forward in front of the larynx.
- Maxillomandibular advancement (MMA). MMA is the most effective sleep apnea surgical procedure currently available, with reduction of the AHI to less than 15 in over 90% of patients, and reduction of AHI to <5 in ~45% of patients. MMA was once thought to be fairly invasive, but has shown to be less painful, in general, than a UPPP soft palate procedure. The associated surgical risks are low, including bleeding, infection, malocclusion, and permanent numbness of the chin and lip. In general, patient perceptions of surgical outcome have been very favorable.
The role of surgery in the treatment of sleep apnea has been questioned repeatedly as the long term success rate of the procedures has come into question. Patient selection in the past was oftentimes quite poor, resulting in poor overall results. Potential surgical candidates should now be extensively examined to assure the site of obstruction is clearly evident prior to any surgical intervention.The patient's age, weight and other factors may make them a bad candidate for surgery. When a patient can tolerate it, positive air pressure treatment is the gold standard. However, surgical intervention is a viable option for those patients who cannot, or refuse, to utilize CPAP.
A small randomized controlled trial reported that compression stockings reduced the number of apneas and hypopnea, perhaps by "prevention of fluid accumulation in the legs during the day, and its nocturnal displacement into the neck at night."
Oropharyngeal muscle exercises
One study showed that playing the didgeridoo may reduce snoring and daytime sleepiness due to OSA. Since OSA is sometimes caused by hypotonicity (low tone) in the muscles of the throat, playing the didgeridoo may improve symptoms of sleep apnea by exercising muscles of the throat and increasing tone.
A study published in 2009 tested the effect of a set of oropharyngeal exercises developed from exercises used by speech-language pathologists to improve swallowing function. Participants with moderate OSA who performed the exercises every day showed a significant decrease in snoring frequency, snoring intensity, daytime sleepiness, sleep quality score, neck circumference, and AHI score when compared with a control group who performed sham exercises. The improvement in OSA shown by this group was comparable to the improvement shown in patients who use oral appliances to treat this condition.
Although this study was not designed to determine which specific exercises were beneficial, an editorial response to this study in the same journal argues that only 2 of the set of exercises were likely capable of effecting the improvements they reported. These 2 exercises included sucking the tongue upward against the palate for a total of 3 minutes throughout the day, and inflating a balloon by blowing forcefully and then breathing in deeply through the nose, repeated 5 times without removing the balloon from the mouth. The tongue exercise is intended to increase the strength of tongue protrusion, and the balloon exercise is intended to increase the strength of the pharyngeal wall. Although more research is needed to clarify the effects of oropharyngeal exercise on OSA, this recent study suggests a promising new approach to treating the condition.
Many people benefit from sleeping at a 30 degree elevation of the upper body or higher, as if in a recliner. Doing so helps prevent the gravitational collapse of the airway. Lateral positions (sleeping on a side), as opposed to supine positions (sleeping on the back), are also recommended as a treatment for sleep apnea, largely because the gravitational component is smaller than in the lateral position. A 30 degree elevation of the upper body can be achieved by sleeping in a recliner, an adjustable bed, or a bed wedge placed under the mattress. This approach can easily be used in combination with other treatments and may be particularly effective in very obese people.
Many studies indicate that it is the effect of a "fight or flight" response on the body that happens with each apneic event that increases health risks and consequences in OSA. The fight or flight response causes many hormonal changes in the body; those changes, coupled with the low oxygen saturation level of the blood, cause damage to the body over time.
Although it takes some trial and error, most patients find a combination of treatments which reduce apnea events and improve their overall health, energy, and well-being. Without treatment, the sleep deprivation and lack of oxygen caused by sleep apnea increases health risks such as cardiovascular disease, high blood pressure, stroke, diabetes, clinical depression, weight gain and obesity.
The most serious consequence of untreated OSA is to the heart. Sleep apnea sufferers have a 30% higher risk of heart attack or death than those unaffected. In severe and prolonged cases, there are increases in pulmonary pressures that are transmitted to the right side of the heart. This can result in a severe form of congestive heart failure known as cor pulmonale. One prospective study showed that patients with OSA, compared with healthy controls, initially had statistically significant increases in vascular endothelial growth factor (P=.003) and significantly lower levels of nitrite-nitrate (P=.008), which might be pathogenic factors in the cardiovascular complications of OSA. These factors reversed to normal levels after 12 weeks of treatment by CPAP, but further long-term trials are needed to assess the impact of this therapy.
Elevated arterial pressure (i.e., hypertension) can be a consequence of OSA syndrome. When hypertension is caused by OSA, it is distinctive in that, unlike most cases (so-called essential hypertension), the readings do not drop significantly when the individual is sleeping. Stroke is also known to be associated with OSA.
- Marfan syndrome
- Respiratory disturbance index (RDI)
- Upper airway resistance syndrome, related condition whose existence is questioned
- ^ AASM (2001). The International Classification of Sleep Disorders, Revised. Westchester, Illinois: American Academy of Sleep Medicine,. pp. 52–8. http://www.esst.org/adds/ICSD.pdf. Retrieved 2010-09-11.
- ^ Gale SD, Hopkins RO (2004). "Effects of hypoxia on the brain: neuroimaging and neuropsychological findings following carbon monoxide poisoning and obstructive sleep apnea". J Int Neuropsychol Soc 10 (1): 60–71. doi:10.1017/S1355617704101082. PMID 14751008. http://journals.cambridge.org/abstract_S1355617704101082.
- ^ Halbower AC, Degaonkar M, Barker PB, et al. (August 2006). "Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury". PLoS Med. 3 (8): e301. doi:10.1371/journal.pmed.0030301. PMC 1551912. PMID 16933960. http://dx.plos.org/10.1371/journal.pmed.0030301.
- ^ Natalie Edwards, Colin E. Sullivan, Sleep-Disordered Breathing in Pregnancy, Sleep Medicine Clinics, Volume 3, Issue 1, March 2008, Pages 81-95, ISSN 1556-407X, 10.1016/j.jsmc.2007.10.010. (http://www.sciencedirect.com/science/article/pii/S1556407X0700121X)
- ^ Sleep Apnea: Risk Factors, Mayo Clinic, June 29, 2010, Retrieved November 4, 2010.
- ^ Shamsuzzaman AS, Gersh BJ, Somers VK (October 8, 2003). "Obstructive sleep apnea: implications for cardiac and vascular disease". Journal of the American Medical Association 290 (14): 1906–14. doi:10.1001/jama.290.14.1906. PMID 14532320.
- ^ Sloan GM (March 2000). "Posterior pharyngeal flap and sphincter pharyngoplasty: the state of the art". Cleft Palate Craniofac. J. 37 (2): 112–22. doi:10.1597/1545-1569(2000)037<0112:PPFASP>2.3.CO;2. PMID 10749049.
- ^ Pugh, M.B. et al. (2000). Apnea. Stedman's Medical Dictionary (27th ed.) Retrieved June 18, 2006 from STAT!Ref Online Medical Library database.
- ^ Liao YF, Noordhoff MS, Huang CS, et al. (March 2004). "Comparison of obstructive sleep apnea syndrome in children with cleft palate following Furlow palatoplasty or pharyngeal flap for velopharyngeal insufficiency". Cleft Palate Craniofac. J. 41 (2): 152–6. doi:10.1597/02-162. PMID 14989690.
- ^ McWilliams, Betty Jane; Peterson-Falzone, Sally J.; Hardin-Jones, Mary A.; Karnell, Michael P. (2001). Cleft palate speech (3rd ed.). St. Louis: Mosby. ISBN 0-8151-3153-4.
- ^ FAQ on www.sleepeducation.com
- ^ http://www.sleep-journal.com/article/S1389-9457(10)00379-5/abstract
- ^ American Academy of Sleep Medicine Task Force, 1999
- ^ Mulgrew AT, Fox N, Ayas NT, Ryan CF (2007). "Diagnosis and initial management of obstructive sleep apnea without polysomnography: a randomized validation study". Ann. Intern. Med. 146 (3): 157–66. PMID 17283346. http://www.annals.org/cgi/content/full/146/3/157/. [dead link]
- ^ Flemons WW, Whitelaw WA, Brant R, Remmers JE (1994). "Likelihood ratios for a sleep apnea clinical prediction rule". Am. J. Respir. Crit. Care Med. 150 (5 Pt 1): 1279–85. PMID 7952553.
- ^ Whitelaw WA, Brant RF, Flemons WW (2005). "Clinical usefulness of home oximetry compared with polysomnography for assessment of sleep apnea.". Am J Respir Crit Care Med 171 (2): 188–93. doi:10.1164/rccm.200310-1360OC. PMID 15486338. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15486338. Review in: ACP J Club. 2005 Jul-Aug;143(1):21
- ^ Littner M, Hirshkowitz M, Davila D, Anderson WM, Kushida CA, Woodson BT et al. (2002). "Practice parameters for the use of auto-titrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome. An American Academy of Sleep Medicine report.". Sleep 25 (2): 143–7. PMID 11902424.
- ^ "First Effective Drug For Sleep Disorder Identified". ScienceDaily.com. June 2003. http://www.sciencedaily.com/releases/2003/06/030605081837.htm.
- ^ Easier Treatment For Sleep Apnea: Healthy For Life from the Eyewitness News Newsroom
- ^ Antidepressant Is Promising for Sleep Apnea
- ^ Carley DW, Olopade C, Ruigt GS, Radulovacki M (January 2007). "Efficacy of mirtazapine in obstructive sleep apnea syndrome". Sleep 30 (1): 35–41. PMID 17310863.
- ^ StreetInsider.com - Cypress Bioscience (CYPB) Says Phase IIa Trials Don't Support Continuing Development Program to Evaluate Combinations of Mirtazapine
- ^ "Novel Drug Therapy For Sleep Apnea". ScienceDaily.com. October 2004. http://www.sciencedaily.com/releases/2004/10/041005073612.htm.
- ^ Veasey SC (2003). "Serotonin agonists and antagonists in obstructive sleep apnea: therapeutic potential". Am J Respir Med 2 (1): 21–9. PMID 14720019.
- ^ Hanzel DA, Proia NG, Hudgel DW (August 1991). "Response of obstructive sleep apnea to fluoxetine and protriptyline". Chest 100 (2): 416–21. doi:10.1378/chest.100.2.416. PMID 1864117. http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=1864117.
- ^ Schmidt HS (1983). "L-tryptophan in the treatment of impaired respiration in sleep". Bull Eur Physiopathol Respir 19 (6): 625–9. PMID 6360258.
- ^ Brownell LG, West P, Sweatman P, Acres JC, Kryger MH (October 1982). "Protriptyline in obstructive sleep apnea: a double-blind trial". N. Engl. J. Med. 307 (17): 1037–42. doi:10.1056/NEJM198210213071701. PMID 6750396. http://content.nejm.org/cgi/content/abstract/307/17/1037.
- ^ Li KK, Powell NB, Riley RW, et al. (2000). "Long-term results of maxillomandibular advancement surgery". Sleep Breath 4 (10 Pt 1): 137–9. doi:10.1055/s-2000-11564. PMID 11037825.
- ^ Sleep apnea
- ^ Redolfi S, Arnulf I, Pottier M, Lajou J, Koskas I, Bradley TD et al. (2011). "Attenuation of Obstructive Sleep Apnea by Compression Stockings in Subjects With Venous Insufficiency.". Am J Respir Crit Care Med. doi:10.1164/rccm.201102-0350OC. PMID 21836140. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21836140.
- ^ Puhan MA, Suarez A, Lo Cascio C, Zahn A, Heitz M, Braendli O (February 2006). "Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial". BMJ 332 (7536): 266–70. doi:10.1136/bmj.38705.470590.55. PMC 1360393. PMID 16377643. http://www.bmj.com/cgi/content/full/332/7536/266.
- ^ a b c Guimaraes KC, Drager LF, Genta PR, Marcondes BF, Lorensi-Filhol G (February 2009). "Effects of Oropharyngeal Exercises on Patients with Moderate Obstructive Sleep Apnea Syndrome". Am J Respir Crit Care Med 179 (10): 962–966. doi:10.1164/rccm.200806-981OC. PMID 19234106. http://ajrccm.atsjournals.org/cgi/content/short/200806-981OCv1?ck=nck.
- ^ Steele CM (February 2009). "On the Plausibility of Upper Airway Remodeling as an Outcome of Orofacial Exercise". Am J Respir Crit Care Med 179 (10): 858–859. doi:10.1164/rccm.200901-0016ED. PMID 19423718. http://ajrccm.atsjournals.org/cgi/content/full/179/10/858.
- ^ Neill AM, Angus SM, Sajkov D, McEvoy RD (January 1997). "Effects of sleep posture on upper airway stability in patients with obstructive sleep apnea". Am. J. Respir. Crit. Care Med. 155 (1): 199–204. PMID 9001312. http://ajrccm.atsjournals.org/cgi/content/abstract/155/1/199.
- ^ The Study Of The Influence Of Sleep Position On Sleep Apnea
- ^ Positioner–a method for preventing sleep apnea
- ^ Szollosi I, Roebuck T, Thompson B, Naughton MT (August 2006). "Lateral sleeping position reduces severity of central sleep apnea / Cheyne-Stokes respiration". Sleep 29 (8): 1045–51. PMID 16944673.
- ^ www.yale.edu
- ^ "Cellular Link Between Sleep Apnea And Atherosclerosis Found". ScienceDaily.com. April 2002. http://www.sciencedaily.com/releases/2002/04/020403025512.htm.
- ^ http://www.schlaflabor-breisgau.de/Bild_gif/Peppard.pdf
- ^ "Sleep Apnea May Increase Risk Of Diabetes". ScienceDaily.com. May 2007. http://www.sciencedaily.com/releases/2007/05/070520183530.htm.
- ^ Schröder CM, O'Hara R (2005). "Depression and Obstructive Sleep Apnea (OSA)". Ann Gen Psychiatry 4 (1): 13. doi:10.1186/1744-859X-4-13. PMC 1181621. PMID 15982424. http://www.annals-general-psychiatry.com/content/4//13.
- ^ N.A. Shah, M.D., N.A. Botros, M.D., H.K. Yaggi, M.D., M., V. Mohsenin, M.D., New Haven, Connecticut (May 20, 2007). "Sleep Apnea Increases Risk of Heart Attack or Death by 30%". American Thoracic Society. http://www.thoracic.org/sections/publications/press-releases/conference/articles/2007/press-releases/sleep-apnea-increases-risk-of-heart-attack-or-death-by-30.html.
- ^ Cifci TU, et al (January 2011). "Consequences of hypoxia-reoxygenation phenomena in patients with obstructive sleep apnea syndrome". Annals of Saudi Medicine 31 (1): 14–18. doi:10.4103/0256-4947.75772.
- ^ Bahammam A (January 2011). "Obstructive sleep apnea: From Simple Upper Airway Obstruction to Systemic Inflammation". Annals of Saudi Medicine 31 (1): 1–2. doi:10.4103/0256-4947.75770.
- ^ Silverberg DS, Iaina A and Oksenberg A (January 2002). "Treating Obstructive Sleep Apnea Improves Essential Hypertension and Quality of Life". American Family Physician 65 (2): 229–36. PMID 11820487. http://www.aafp.org/afp/20020115/229.html.
- ^ Grigg-Damberger M. (2006-02). "Why a polysomnogram should become part of the diagnostic evaluation of stroke and transient ischemic attack". Journal of Clinical Neurophysiology 23 (1): 21–38. doi:10.1097/01.wnp.0000201077.44102.80. PMID 16514349.
- ^ Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V (November 2005). "Obstructive sleep apnea as a risk factor for stroke and death". N. Engl. J. Med. 353 (19): 2034–41. doi:10.1056/NEJMoa043104. PMID 16282178. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16282178&promo=ONFLNS19.
Pathology of the nervous system, primarily CNS (G04–G47, 323–349) InflammationBoth/either Brain/
encephalopathyBasal ganglia disease: Parkinsonism (PD, Postencephalitic, NMS) · PKAN · Tauopathy (PSP) · Striatonigral degeneration · Hemiballismus · HD · OADyskinesia: Dystonia (Status dystonicus, Spasmodic torticollis, Meige's, Blepharospasm) · Chorea (Choreoathetosis) · Myoclonus (Myoclonic epilepsy) · AkathesiaEpisodic/
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