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|Classification and external resources|
Obstructive sleep apnea
|Classification and external resources|
Obstructive sleep apnea
Sleep apnea (or sleep apnoea in British English; //) is a type of sleep disorder characterized by pauses in breathing or instances of shallow or infrequent breathing during sleep. Each pause in breathing, called an apnea, can last from at least ten seconds to several minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally shallow breathing event is called a hypopnea. Sleep apnea is classified as a dyssomnia, meaning abnormal behavior or psychological events occur during sleep. When breathing is paused, carbon dioxide is building up the bloodstream. Chemoreceptors in the blood stream note the high carbon dioxide levels. The brain is signaled to wake the person sleeping and breathe in air. Breathing normally will restore oxygen levels and the person will fall asleep again. Sleep apnea is often diagnosed with an overnight sleep test called a polysomnogram, or "sleep study".
There are three forms of sleep apnea: central (CSA), obstructive (OSA), and complex or mixed sleep apnea (i.e., a combination of central and obstructive) constituting 0.4%, 84% and 15% of cases respectively. In CSA, breathing is interrupted by a lack of respiratory effort; in OSA, breathing is interrupted by a physical block to airflow despite respiratory effort, and snoring is common. According to the National Institutes of Health, 12 million Americans have OSA. There are more cases of sleep apnea still because people either do not report the condition or do not know they have sleep apnea.
Regardless of type, an individual with sleep apnea is rarely aware of having difficulty breathing, even upon awakening. Sleep apnea is recognized as a problem by others witnessing the individual during episodes or is suspected because of its effects on the body (sequelae). Symptoms may be present for years (or 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.
Sleep apnea affects not only adults but some children as well. As stated by El-Ad, "patients complain about excessive daytime sleepiness (EDS) and impaired alertness". In other words, common effects of sleep apnea include daytime fatigue, a slower reaction time, and vision problems. OSA may increase risk for driving accidents and work-related accidents. If OSA is not treated, one has an increased risk of other health problems such as diabetes. Even death could occur from untreated OSA due to lack of oxygen to the body. Moreover, patients are examined using “standard test batteries” in order to further identify parts of the brain that are affected by sleep apnea. Tests have shown that certain parts of the brain cause different effects. The “executive functioning” part of the brain affects the way the patient plans and initiates tasks. Second, the part of the brain that deals with attention causes difficulty in paying attention, working effectively and processing information when in a waking state. Thirdly, the part of the brain that uses memory and learning is also affected. Due to the disruption in daytime cognitive state, behavioral effects are also present. This includes moodiness, belligerence, as well as a decrease in attentiveness and drive. Another symptom of sleep apnea is waking up in sleep paralysis. In severe cases, the fear of sleep due to sleep paralysis can lead to insomnia. These effects become very hard to deal with, thus the development of depression may transpire. There is also evidence that the risk of diabetes among those with moderate or severe sleep apnea is higher. There is also increasing evidence that sleep apnea may also lead to liver function impairment, particularly fatty liver diseases (see steatosis). Finally, because there are many factors that could lead to some of the effects previously listed, some patients are not aware that they suffer from sleep apnea and are either misdiagnosed, or just ignore the symptoms altogether.
Sleep Apnea Awareness Day is April 18 every year. April 18 recognizes Colin Sullivan's invention of the CPAP machine and technology. In 1981 he released his study with results of five patients suffering from sleep apnea and successfully used the CPAP machine. The American Sleep Apnea Association (ASAA) believes the CPAP machine greatly changed the treatment and regulation of sleep apnea. Research found using this sleep technology allowed for a better night's sleep and reduced related conditions like diabetes, depression, and hypertension.
The diagnosis of sleep apnea is based on the conjoint evaluation of clinical symptoms (e.g. excessive daytime sleepiness and fatigue) and of the results of a formal sleep study (polysomnography, or reduced channels home based test). The latter aims at establishing an "objective" diagnosis indicator linked to the quantity of apneic events per hour of sleep (Apnea Hypopnea Index(AHI), or Respiratory Disturbance Index (RDI)), associated to a formal threshold, above which a patient is considered as suffering from sleep apnea, and the severity of their sleep apnea can then be quantified. Mild OSA (Obstructive Sleep Apneas) ranges from 5 to 14.9 events per hour of sleep, moderate OSA falls in the range of 15–29.9 events per hour of sleep, and severe OSA would be a patient having over 30 events per hour of sleep.
Nevertheless, due to the number and variability in the actual symptoms and nature of apneic events (e.g., hypopnea vs apnea, central vs obstructive), the variability of patients' physiologies, and the intrinsic imperfections of the experimental setups and methods, this field is opened to debate. Within this context, the definition of an apneic event depends on several factors (e.g. patient's age) and account for this variability through a multi-criteria decision rule described in several, sometimes conflicting, guidelines. One example of a commonly adopted definition of an apnea (for an adult) includes a minimum 10 second interval between breaths, with either a neurological arousal (a 3-second or greater shift in EEG frequency, measured at C3, C4, O1, or O2) or a blood oxygen desaturation of 3–4% or greater, or both arousal and desaturation.
Oximetry, which may be performed overnight in a patient's home, is an easier alternative to formal sleep study (polysomnography). In one study, normal overnight oximetry was very sensitive and so if normal, sleep apnea was unlikely. In addition, home oximetry may be equally effective in guiding prescription for automatically self-adjusting continuous positive airway pressure.
Obstructive sleep apnea (OSA) is the most common category of sleep-disordered breathing. The muscle tone of the body ordinarily relaxes during sleep, and at the level of the throat the human airway is composed of collapsible walls of soft tissue which can obstruct breathing during sleep. Mild occasional sleep apnea, such as many people experience during an upper respiratory infection, may not be important, but chronic severe obstructive sleep apnea requires treatment to prevent low blood oxygen (hypoxemia), sleep deprivation, and other complications.
Individuals with low muscle tone and soft tissue around the airway (e.g., because of obesity) and structural features that give rise to a narrowed airway are at high risk for obstructive sleep apnea. The elderly are more likely to have OSA than young people. Men are more likely to suffer sleep apnea than women and children are, though it is not uncommon in the last two population groups.
The risk of OSA rises with increasing body weight, active smoking and age. In addition, patients with diabetes or "borderline" diabetes have up to three times the risk of having OSA.
Some treatments involve lifestyle changes, such as avoiding alcohol or muscle relaxants, losing weight, and quitting smoking. 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 in the lateral position. Some people benefit from various kinds of oral appliances to keep the airway open during sleep. Continuous positive airway pressure (CPAP) is the most effective treatment for severe obstructive sleep apnea but oral appliances are considered a first line approach equal to CPAP for mild to moderate sleep apnea according to the AASM parameters of care. There are also surgical procedures to remove and tighten tissue and widen the airway.
Snoring is a common finding in people with this syndrome. Snoring is the turbulent sound of air moving through the back of the mouth, nose, and throat. Although not everyone who snores is experiencing difficulty breathing, snoring in combination with other conditions such as overweight and obesity has been found to be highly predictive of OSA risk. The loudness of the snoring is not indicative of the severity of obstruction, however. If the upper airways are tremendously obstructed, there may not be enough air movement to make much sound. Even the loudest snoring does not mean that an individual has sleep apnea syndrome. The sign that is most suggestive of sleep apneas occurs when snoring stops.
Other indicators include (but are not limited to): hypersomnolence, obesity BMI >30, large neck circumference (16 in (410 mm) in women, 17 in (430 mm) in men), enlarged tonsils and large tongue volume, micrognathia, morning headaches, irritability/mood-swings/depression, learning and/or memory difficulties, and sexual dysfunction.
The term "sleep-disordered breathing" is commonly used in the U.S. to describe the full range of breathing problems during sleep in which not enough air reaches the lungs (hypopnea and apnea). Sleep-disordered breathing is associated with an increased risk of cardiovascular disease, stroke, high blood pressure, arrhythmias, diabetes, and sleep deprived driving accidents. When high blood pressure is caused by OSA, it is distinctive in that, unlike most cases of high blood pressure (so-called essential hypertension), the readings do not drop significantly when the individual is sleeping. Stroke is associated with obstructive sleep apnea.
It has been revealed that people with OSA show tissue loss in brain regions that help store memory, thus linking OSA with memory loss. Using magnetic resonance imaging (MRI), the scientists discovered that sleep apnea patients' mammillary bodies were nearly 20 percent smaller, particularly on the left side. One of the key investigators hypothesized that repeated drops in oxygen lead to the brain injury.
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In pure central sleep apnea or Cheyne–Stokes respiration, the brain's respiratory control centers are imbalanced during sleep. Blood levels of carbon dioxide, and the neurological feedback mechanism that monitors them, do not react quickly enough to maintain an even respiratory rate, with the entire system cycling between apnea and hyperpnea, even during wakefulness. The sleeper stops breathing and then starts again. There is no effort made to breathe during the pause in breathing: there are no chest movements and no struggling. After the episode of apnea, breathing may be faster (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases and absorb more oxygen.
While sleeping, a normal individual is "at rest" as far as cardiovascular workload is concerned. Breathing is regular in a healthy person during sleep, and oxygen levels and carbon dioxide levels in the bloodstream stay fairly constant. The respiratory drive is so strong that even conscious efforts to hold one's breath do not overcome it. Any sudden drop in oxygen or excess of carbon dioxide (even if tiny) strongly stimulates the brain's respiratory centers to breathe.
In central sleep apnea, the basic neurological controls for breathing rate malfunction and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. If the pause in breathing is long enough, the percentage of oxygen in the circulation will drop to a lower than normal level (hypoxaemia) and the concentration of carbon dioxide will build to a higher than normal level (hypercapnia). In turn, these conditions of hypoxia and hypercapnia will trigger additional effects on the body. Brain cells need constant oxygen to live, and if the level of blood oxygen goes low enough for long enough, the consequences of brain damage and even death will occur. Fortunately, central sleep apnea is more often a chronic condition that causes much milder effects than sudden death. The exact effects of the condition will depend on how severe the apnea is and on the individual characteristics of the person having the apnea. Several examples are discussed below, and more about the nature of the condition is presented in the section on Clinical Details.
In any person, hypoxia and hypercapnia have certain common effects on the body. The heart rate will increase, unless there are such severe co-existing problems with the heart muscle itself or the autonomic nervous system that makes this compensatory increase impossible. The more translucent areas of the body will show a bluish or dusky cast from cyanosis, which is the change in hue that occurs owing to lack of oxygen in the blood ("turning blue"). Overdoses of drugs that are respiratory depressants (such as heroin, and other opiates) kill by damping the activity of the brain's respiratory control centers. In central sleep apnea, the effects of sleep alone can remove the brain's mandate for the body to breathe.
Some people with sleep apnea have a combination of both types. When obstructive sleep apnea syndrome is severe and longstanding, episodes of central apnea sometimes develop. The exact mechanism of the loss of central respiratory drive during sleep in OSA is unknown but is most commonly related to acid–base and CO2 feedback malfunctions stemming from heart failure. There is a constellation of diseases and symptoms relating to body mass, cardiovascular, respiratory, and occasionally, neurological dysfunction that have a synergistic effect in sleep-disordered breathing. In some cases, a side effect from the lack of sleep is a mild case of Excessive Daytime Sleepiness (EDS) where the subject has had minimal sleep and this extreme fatigue over time takes its toll on the subject. The presence of central sleep apnea without an obstructive component is a common result of chronic opiate use (or abuse) owing to the characteristic respiratory depression caused by large doses of narcotics.
Complex sleep apnea has recently been described by researchers as a novel presentation of sleep apnea.[dubious ] Patients with complex sleep apnea exhibit OSA, but upon application of positive airway pressure the patient exhibits persistent central sleep apnea. This central apnea is most commonly noted while on CPAP therapy after the obstructive component has been eliminated. This has long been seen in sleep laboratories and has historically been managed either by CPAP or BiLevel therapy. Adaptive servo-ventilation (ASV) modes of therapy have been introduced to attempt to manage this complex sleep apnea. Studies have demonstrated marginally superior performance of the adaptive servo ventilators in treating Cheyne–Stokes breathing; however, no longitudinal studies have yet been published, nor have any results been generated that suggest any differential outcomes versus standard CPAP therapy. At the AARC 2006 in Las Vegas, NV, researchers reported successful treatment of hundreds of patients on ASV therapy; however, these results have not been reported in peer-reviewed publications as of July 2007[update].
It is suggested that transient central apnea produced during CPAP titration (the so-called "complex sleep apnea") is "…transient and self-limited." The central apneas may in fact be secondary to sleep fragmentation during the titration process. As of July 2007[update], there has been no alternate convincing evidence produced that these central sleep apnea events associated with CPAP therapy for obstructive sleep apnea are of any significant pathophysiologic importance.[dated info]
It has been proposed to add dead space to positive airway pressure for treatment of complex sleep-disordered breathing.
Treatment often starts with behavioral therapy. Many patients are told to avoid alcohol, sleeping pills, and other sedatives, which can relax throat muscles, contributing to the collapse of the airway at night. As sleep apnea is inherently worse in the supine position for many patients (positional sleep apnea), sleeping on one's side is often advised.
Possibly owing to changes in pulmonary oxygen stores, sleeping on one's side (as opposed to on one's back) has been found to be helpful for central sleep apnea with Cheyne–Stokes respiration.
For moderate to severe sleep apnea, the most common treatment is the use of a continuous positive airway pressure (CPAP) or automatic positive airway pressure (APAP) device which 'splints' the patient's airway open during sleep by means of a flow of pressurized air into the throat. The patient typically wears a plastic facial mask, which is connected by a flexible tube to a small bedside CPAP machine. The CPAP machine generates the required air pressure to keep the patient's airways open during sleep. While pure CPAP machines require one to input a desired pressure (usually determined in an overnight sleep study), an APAP machine will automatically titrate the air pressure as needed to minimize apneas and hypopneas. Advanced models may warm or humidify the air and monitor the patient's breathing to ensure proper treatment.
Retail cost for CPAP machines is between $300–$2,000. This is without insurance payment. Many health plans cover part of CPAP machines and masks costs. The extra CPAP supplies include the mask, tubes, and filters averaging between $300–$800 per year. CPAP machine costs may be higher if a humidifier is included. Humidifiers add comfort to using the device and some reported a decrease in side effects.
Although CPAP therapy is extremely effective in reducing apneas and less expensive than other treatments, some patients find it extremely uncomfortable. Patients complain of feeling trapped, having chest discomfort, and skin or nose irritation. Other side effects a patient may experience are dry mouth, dry nose, nosebleeds, sore lips and gums. Many patients refuse to continue the therapy or fail to use their CPAP machines on a nightly basis, especially in the long term. One way to ensure CPAP therapy remains comfortable and effective for patients is to carefully consider the right CPAP face mask to be used. CPAP masks come in different shapes, sizes and materials to ensure effective treatment for obstructive sleep apnea. It is important to select the right mask to fit each patient.
It is not clear that CPAP reduces hypertension or cardiovascular events in patients who do not have daytime sleepiness; however, the lack of benefit may be partly due to noncompliance with therapy.
In 2014 the U.S. Food and Drug Administration granted pre-market approval for use of an upper airway stimulation system in patients who cannot use a continuous positive airway pressure device. The system senses respiration and increases muscle tone at the back of the tongue by delivering a mild electrical pulse so that the tongue will not block the airway. Patients use a handheld controller to switch the device on before sleep. Stimulation is provided by an implantable pulse generator, analogous to the power supply of a heart pacemaker. Prior to approval of this neuromodulation device, a clinical trial was conducted with results appearing in the New England Journal of Medicine. 
There is limited evidence for medication but acetazolamide "may be considered" for the treatment of central sleep apnea; it also found that zolpidem and triazolam may be considered for the treatment of central sleep apnea, but "only if the patient does not have underlying risk factors for respiratory depression". Low doses of oxygen are also used as a treatment for hypoxia but are discouraged due to side effects.
General dentists can fabricate an oral appliance. The oral appliance, called a mandibular advancement splint, is a custom-made mouthpiece that shifts the lower jaw forward and opens the bite slightly, which opens up the airway. Oral appliance therapy (OAT) is usually successful in patients with mild to moderate obstructive sleep apnea. OAT is a relatively new treatment option for sleep apnea in the United States, but it is much more common in Canada and Europe.
Several surgical procedures (sleep surgery) are used to treat sleep apnea, although they are normally a second line of treatment for those who reject CPAP treatment or are not helped by it. Surgical treatment for obstructive sleep apnea needs to be individualized to address all anatomical areas of obstruction. Often, correction of the nasal passages needs to be performed in addition to correction of the oropharynx passage. Septoplasty and turbinate surgery may improve the nasal airway. Tonsillectomy and uvulopalatopharyngoplasty (UPPP or UP3) are available to address pharyngeal obstruction. Base-of-tongue advancement by means of advancing the genial tubercle of the mandible may help with the lower pharynx. Many other treatments are available, including hyoid bone myotomy and suspension and various radiofrequency
Other surgery options may attempt to shrink or stiffen excess tissue in the mouth or throat; procedures done at either a doctor's office or a hospital. Small shots or other treatments, sometimes in a series, are used for shrinkage, while the insertion of a small piece of stiff plastic is used in the case of surgery whose goal is to stiffen tissues.
The Pillar Procedure is a minimally invasive treatment for snoring and obstructive sleep apnea. This procedure was FDA indicated in 2004. During this procedure, three to six or more Dacron (the material used in permanent sutures) strips are inserted into the soft palate, using a modified syringe and local anesthetic. While the procedure was initially approved for the insertion of three "pillars" into the soft palate, it was found that there was a significant dosage response to more pillars, with appropriate candidates. After this brief and virtually painless outpatient operation, which usually lasts no more than 30 minutes, the soft palate is more rigid and snoring and sleep apnea can be reduced. This procedure addresses one of the most common causes of snoring and sleep apnea — vibration or collapse of the soft palate (the soft part of the roof of the mouth). If there are other factors contributing to snoring or sleep apnea, such as the nasal airway or an enlarged tongue, it will likely need to be combined with other treatments to be more effective.
The Stanford Center for Excellence in Sleep Disorders Medicine achieved a 95% cure rate of sleep apnea patients by surgery. Maxillomandibular advancement (MMA) is considered the most effective surgery for sleep apnea patients, because it increases the posterior airway space (PAS). The main benefit of the operation is that the oxygen saturation in the arterial blood increases. In a study published in 2008, 93.3.% of surgery patients achieved an adequate quality of life based on the Functional Outcomes of Sleep Questionnaire (FOSQ). Surgery led to a significant increase in general productivity, social outcome, activity level, vigilance, intimacy, and intercourse. Overall risks of MMA surgery are low: The Stanford University Sleep Disorders Center found 4 failures in a series of 177 patients, or about one out of 44 patients. However, health professionals are often unsure as to who should be referred for surgery and when to do so: some factors in referral may include failed use of CPAP or device use; anatomy which favors rather than impeding surgery; or significant craniofacial abnormalities which hinder device use. Maxillomandibular advancement surgery is often combined with Genioglossus Advancement, as both are skeletal surgeries for sleep apnea.
Several inpatient and outpatient procedures use sedation. Many drugs and agents used during surgery to relieve pain and to depress consciousness remain in the body at low amounts for hours or even days afterwards. In an individual with either central, obstructive or mixed sleep apnea, these low doses may be enough to cause life-threatening irregularities in breathing or collapses in a patient’s airways. Use of analgesics and sedatives in these patients postoperatively should therefore be minimized or avoided.
Surgery on the mouth and throat, as well as dental surgery and procedures, can result in postoperative swelling of the lining of the mouth and other areas that affect the airway. Even when the surgical procedure is designed to improve the airway, such as tonsillectomy and adenoidectomy or tongue reduction, swelling may negate some of the effects in the immediate postoperative period. Once the swelling resolves and the palate becomes tightened by postoperative scarring, however, the full benefit of the surgery may be noticed.
A sleep apnea patient undergoing any medical treatment must make sure his or her doctor and anesthetist are informed about the sleep apnea. Alternative and emergency procedures may be necessary to maintain the airway of sleep apnea patients. If an individual suspects he or she may have sleep apnea, communication with their doctor about possible preprocedure screening may be in order.
Other studies have also suggested that strengthening the muscles around the upper airway may combat sleep apnea. A 2001 study investigated changes after Tongue Muscle Training (ZMT®) in respiratory parameters during night-time sleep of patients with increased respiratory disease index. 40 sleep apnea patients, which up to this time had been treated with nCPAP, underwent electrostimulation of the suprahyoidal musculature for 5 weeks with a special EMS-device. The apnea, hypopnea and desaturation indexes were reduced in 26 of the 40 patients (65%) by an average of approximately one half. A 2005 study in the British Medical Journal found that learning and practicing the didgeridoo helped reduce snoring and sleep apnea as well as daytime sleepiness. This appears to work by strengthening muscles in the upper airway, thus reducing their tendency to collapse during sleep. A 2009 study published in the American Journal of Respiratory and Clinical Care Medicine found that patients who practiced a series of tongue and throat exercises for 30 minutes a day showed a marked decline in sleep apnea symptoms after three months. Patients experienced an average of 39% fewer apnea episodes after successfully completing the treatments. 
Cannabis derivatives have also been studied in the treatment of sleep apnea. A 2002 study found that orally administered THC was able to stabilize respiration in rats and bulldogs during all sleep stages, decreasing apnea indexes during NREM and REM sleep stages by 42% and 58% respectively. A 2013 proof of concept trial found that dronabinol (synthetic THC) was able to reduce apnea indexes by 32% on average in the 17 human subjects that were studied. Lead study author David Carley subsequently received a $5 million grant from the National Institutes of Health (NIH) to conduct a Phase II clinical trial.
The Wisconsin Sleep Cohort Study estimated in 1993 that roughly one in every 15 Americans was affected by at least moderate sleep apnea. It also estimated that in middle-age as many as nine percent of women and 24 percent of men were affected, undiagnosed and untreated.
The costs of untreated sleep apnea reach further than just health issues. It is estimated that in the U.S. the average untreated sleep apnea patient's annual health care costs $1,336 more than an individual without sleep apnea. This may cause $3.4 billion/year in additional medical costs. Whether medical cost savings occur with treatment of sleep apnea remains to be determined.
A 2012 study has shown that hypoxia (an inadequate supply of oxygen) that characterizes sleep apnea promotes angiogenesis which increase vascular and tumor growth, which in turn results in a 4.8 times higher incidence of cancer mortality.
The clinical picture of this condition has long been recognized as a character trait, without an understanding of the disease process. The term "Pickwickian syndrome" that is sometimes used for the syndrome was coined by the famous early 20th century physician, William Osler, who must have been a reader of Charles Dickens. The description of Joe, "the fat boy" in Dickens's novel The Pickwick Papers, is an accurate clinical picture of an adult with obstructive sleep apnea syndrome.
The early reports of obstructive sleep apnea in the medical literature described individuals who were very severely affected, often presenting with severe hypoxemia, hypercapnia and congestive heart failure.
The management of obstructive sleep apnea was revolutionized with the introduction of continuous positive airway pressure (CPAP), first described in 1981 by Colin Sullivan and associates in Sydney, Australia. The first models were bulky and noisy, but the design was rapidly improved and by the late 1980s CPAP was widely adopted. The availability of an effective treatment stimulated an aggressive search for affected individuals and led to the establishment of hundreds of specialized clinics dedicated to the diagnosis and treatment of sleep disorders. Though many types of sleep problems are recognized, the vast majority of patients attending these centers have sleep-disordered breathing.
Sleep apnea affects all ages including children. There are some specific factors that could increase one's chance of acquiring sleep apnea and include: male, overweight, obese, over the age of 40, large neck size (greater than 16-17 inches), enlarged tonsils, enlarged tongue, small jaw bone, family history of sleep apnea, gastroesophogeal reflux, deviated septum causing nasal obstruction, allergies, and sinus problems. The use of alcohol, sedative or tranquilizers will endure relaxation of the throat. People who smoke are three times more likely to suffer from sleep apnea than a nonsmoker. All the factors above may contribute to Obstructive Sleep Apnea. Central Sleep Apnea is more influenced by being male, being older than 65 years, having heart disorders such as atrial fibrillation, and stroke or brain tumor. Brain tumors may cause the brain's ability regulate normally breathing.