Sleep Apnea

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Definition and Types

Sleep apnea, sometimes spelled “apnoea” – one of the most potentially dangerous sleep disorders – is when the patient stops breathing during regular sleep. The term apnea literally means “without breath”. The period of stoppage is usually short (a few seconds) before breathing resumes. The seriousness of apnea varies considerably and depends on how long the sleep stoppages are how many happen. Also referred to as sleep-disordered breathing, or SDB, apnea occurs widely in adults and children. Experts estimate apnea affects 1 in 15 people or 18 million Americans. Men are more susceptible to sleep apnea than women. “All-cause” mortality risk increases significantly with apnea. The worse the apnea, the higher the risk of death from a number of factors.

There are three types of sleep apnea: central sleep apnea, obstructive sleep apnea, and complex sleep apnea. Obstructive sleep apnea is the most common type.

Obstructive sleep apnea (OSA) is an obstruction of the airway passage that results in a decreased level of oxygen in the blood. The obstructions cause a choking or gasping along with loud snoring during sleep. These choking and gasping episodes briefly arouse the person and can happen as frequently as 20 to 30 times per hour. For this reason a person with sleep apnea cannot get a good night’s rest. Apnea can also cause a headache in the morning, a dry mouth, tiredness during the day, and reduced libido. Central sleep apnea has similar characteristics to OSA, but lacks the loud snoring aspect. In both cases the person awakes suddenly during the night choking or gasping for air.

The reasons why some people are afflicted with sleep apnea are not well understood. Researchers believe there are genetic components. Identification of a single gene is not likely and the current theory points to multiple genes as a plausible cause. One study demonstrated a correlation between obstructive sleep apnea and developing hypertension. The researchers followed individuals with OSA and those that had more than 15 obstructive wake-ups per hour were more likely to develop hypertension within the next 4 years. They also found that those who did not receive treatment had an increased risk for cardiovascular morbidity and mortality. A more recent study suggests that the relationship between apnea and hypertension is because of obesity. Obesity is a major factor in both conditions, while apnea might sometimes be the cause of the hypertension, this condition is more likely caused by high body weight and other factors. High blood pressure and apnea are “co-morbidities”. People with moderate-to-severe OSA can have extensive brain changes, possibly because of the repeated hypoxia. A study presented at the International Stroke Conference in 2012 found that apnea patients have a higher risk of strokes and brain lesions. Many apnea patients also have abnormal swallowing while asleep, although this problem does not typically reach a magnitude where it is considered clinically significant.

Apnea increases the risk of hypertension, regardless of the person’s age, sex, or level of obesity. An article by Greek doctors even playfully called apnea and resistant hypertension “sparring partners”.

Obstructive sleep apnea is correlated with metabolic syndrome, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978322/ although some of the components of metabolic syndrome – diabetes and high cholesterol – did not show correlation with apnea at levels high enough to be considered statistically significant.

Central sleep apnea is much less common, but potentially very dangerous. Central sleep apnea is caused by the failure of brain to transmit signals to the body to breathe, in contrast to obstructive sleep apnea is due to a physical block that obstructs air flow to the lungs.

Cheyne-Stokes respiration is when there is a crescendo – decrescendo pattern of respiration. It occurs in people with congestive heart failure or stroke. Drug or substance abuse, especially over consumption of a respiratory depressant drug may cause central sleep apnea. Alcohol, opiates, benzodiazepines, barbiturates, and some kinds of tranquilizers are respiratory depressants. Breathing at high altitude also causes sleep apnea. In some cases the causes are not known, these cases are “idiopathic central sleep apnea”.

People with certain heart and neuromuscular disorders are also in danger of central sleep apnea.

During an incident of central sleep apnea if the intervals in breathing are too spread apart, the oxygen level in the bloodstream falls below the normal level and the amount of carbon dioxide increases. These abnormal blood levels can cause negative effects on a range of organs; if oxygen level remains low for a long time it can lead to brain damage or even death. The severity of the apnea and the physical fitness of the patient are factors in how well the body can withstand the apnea. Lack of oxygen can cause seizures even in people who have no history of epilepsy and in people with diagnosed epilepsy, but who have it under control, it can cause seizures again and for people with heart diseases it can cause arrhythmias, angina or heart attack.

Complex sleep apnea is a combination of central and obstructive sleep apnea. During complex sleep apnea obstructive apnea and central apnea happen concurrently.

Sleep-related laryngospasm

A related symptom some apnea sufferers get is sleep-related laryngospasm. The sleeper wakes up suddenly and feeling alarmed that he or she is suffocating. Any attempts to speak come out as a wheeze. People who have these spasms often have gastroesophageal reflux, too, leading doctors to hypothesize a connection where the stomach acids reach the larynx and irritate the tissue.

Birth Defects

Cleft lips and palates are the most common birth defects and may affect sleep breathing.  Surgical repair of the airway can help, although sometimes people have apnea and other problems even after surgery.

Treatment of Obstructive Sleep Apnea

The most common treatment for obstructive sleep apnea is termed continuous positive airway pressure or CPAP. The positive pressure is generated by a machine that sits next to the bed and has a mask connected to it that the person wears while sleeping. It forces pressure into the nose and mouth so the airway does not collapse and the person sleeps without choking or gasping awakenings.

CPAP is the most common treatment, but surgery called uvulopalatopharyngoplasty is also an option. Your physician may recommend weight loss, avoidance of alcohol/sedatives, or sleeping in a position other than the back. Removing the tonsils or adenoids also can relieve apnea, especially in children. During the diagnosis process there is a series of tests and the test scores as a measure of severity will determine which course of treatment should be taken. (A sample Berlin Questionairre can be seen here.) For those having trouble with CPAP upon exhaling against the positive pressure there is a modified machine called bilevel positive airway pressure or BiPAP. This device reduces the pressure during exhalation and increases the pressure during inhalation. There have been several pharmacologic treatments tested, but none of them have yielded results similar to treatment with positive airway pressure. If a person is unwilling or unable to use positive airway pressure machines, surgery is an option. The federal government publishes a guideline on “Diagnosis and treatment of obstructive apnea in adults.”

Surgery is not always effective in eliminating the apnea, although it may be beneficial if it reduces the severity of symptoms. Peripheral arterial tonometry – often in a wrist unit the patient can wear to bed – can be used to keep tabs on how the patient is doing following the surgery.

Drugs are not used to directly treat apnea, but there is interest among researchers in developing pharmacological treatment that targets the anatomy and mechanism of the breathing system. A combination of domperidone (normally used to suppress vomiting and nausea) and the antihistimine pseudoephedrine has been tried in a study at a Department of Veterans Affairs hospital. There was also interest in replacing the pseudoephedrine with phenylephrine, a decongestant that is often used in place of pseudoephedrine. This idea was that these drugs would help open passageways for airflow.

Weight loss is often the best way to definitively reduce the effects of apnea, and one advantage is that the patient gets doesn’t have to use the CPAP machine or a mouthguard, both of which tend to be abandoned by patients as being too bothersome.

In 2007 the professional journal Sleep featured a debate about whether mild apnea should be treated. The opposing view (that it should not be treated) rested on low patient compliance with CPAP and the fact that observations of people with mild to moderate apnea who do use the CPAP regularly do not show significant improvements in daytime sleepiness (objective or subjective) and blood pressure.

The author of this article thinks mild apnea should be addressed by trying to get the sleeper to cut alcohol consumption, lose weight, and generally practice good sleep hygiene.

The article advocating treatment, , stated that non-medical intervention is not sufficient and that measures of quality of life improvement due to CPAP are flawed.

Acetazolamide for Apnea

The drug acetazolamide is used to treat mountain sickness (which can include altitude insomnia) and research suggests it might help out people with apnea. The drug, sold under the brand name Diamox, helps increase oxygen levels in the bloodstream. When people ascend to alpine levels, they sometimes have trouble getting enough oxygen. Apnea produces some of the same effects, and Swiss scientists found acetazolamide may help, although this is not yet an accepted treatment.

Treatment of Central Sleep Apnea

Numerous techniques can be used to treat central sleep apnea.Reducing the consumption of respiratory suppressant drugs helps. If the cause is due to a heart or a neuromuscular condition, treatment of the disorder can cure the apnea. Supplemental oxygen and devices like CPAP machines, BiPAP machines, and other ventilators help the respiratory process.

Sleeping in the lateral position (on your side) has been found to be helpful in cases of central sleep apnea. Medications like acetazolamide and theophylline lower the pH level of the blood and help in respiratio. These are used by some doctors to treat sleep apnea patients. People who display symptoms of central sleep apnea should consult a physician at the earliest since delays in treating this disease may lead to life threatening conditions.

Diagnosis and Warnings

Sleep apnea is highly undiagnosed. According to a National Health Institute estimate, only 25 percent of Americans with apnea symptoms sought medical attention over a 4-year period. Indeed, one of the goals of the government’s Healthy People 2020 initiative is to raise this percentage.

A polysomnography is done to detect sleep apnea. In the test the heart, brain and lung activities are tested during sleep to check for abnormalities. Oximetry might also be done to check the blood oxygen level during sleep. In some cases an MRI might also be done.

If a person is experiencing excessive daytime tiredness along with frequent night arousals accompanied by a choking or gasping for air feeling, they should talk to their clinician about sleep apnea. Excessive tiredness can lead to many side effects such as endangering your life or others when driving. Severe mood changes, mental dysfunction, and libido reduction are also associated with sleep apnea.

How Bad?

The Apnea-Hyponea Index was created to quantify the severity of apnea. Under 5 stoppages is considered normal (no apnea). Mild apnea is 5 to 15 incidences per hour, moderate 15-30, and severe greater than 30. There is some controversy because different ways of measuring apnea lead to different results; this is an area where diagnostic standards could be improved.

The other physiological marker useful in determining the severity of apnea is how much oxygen is in the blood. If the blood is saturated with oxygen (carrying as much as it can), the saturation level is 100%. A level below 90% is a sign that something is wrong and not enough oxygen is getting into the blood. A level between 80% and 90% is a sign of mild apnea and a level below 80% is severe.

State laws may require that doctors who know about excessively sleepy people (clinical name for condition: excessive daytime sleepiness) report them to the motor vehicle bureau. The American Thoracic Society (a professional medical group) does not recommend physicians interfere with driving privileges unless the patient has been in a crash or some other event indicates particularly high risk. The society recommends doctors report patients only if they have been in an accident, has apnea that cannot be treated, or refuses treatment within two months of diagnosis.

Neurogenic Tachypnea

Neurogenic tachypnea is a disorder of breathing – is when people breathe fast and shallow. Neurogenic tachypnea is sometimes the beginnings of neurodegenerative disease.  Which is why it is important that your doctor check you out.

Seasonality of Sleep Apnea

Recent epidemiological work has shown that apnea symptoms are worse during the winter. Part of the increase in disordered breathing may be due to allergies and seasonal weight gain (many people get heavier in the winter.) Weather conditions such as high atmospheric pressure (more common in winter), high humidity (more common in summer) and carbon monoxide (more common in urban areas) make apnea worse. Colds and general irritation of the respiratory system are worse in the winter, which can exacerbate apnea symptoms.

Pickwickian Syndrome

In his novel The Pickwick Papers, Charles Dickens describes an obese character Joe The Fat Boy who is sleepy during the daytime and falls asleep at inappropriate times and was difficult to wake up.

A modern writer has identified Joe’s condition as cor pulmonale.

In the 1950’s a medical writer coined the term Pickwickian syndrome to describe sleep-disordered breathing. The character Joe did not appear to actually have apnea as we currently understand it. However, you sometimes see Pickwickian syndrome used to describe sleep disordered breathing.

Medication?

A 2007 article in the Journal of the American Academy of Pain Medicine talks about the connection between opioid medication and sleep apnea. Researchers looked at patients taking opioids for chronic pain and found they had a higher incidence of apnea. This is not surprising as opioids relax the muscles and that includes the throat area. However, these patients did not have the crescendo-decrescendo breath size pattern characteristic of people with central sleep apnea.

There is some evidence that the antidepressant medication mirtazapine (Remeron) helps relieve apnea. This is the most effective drug for apnea found so far, but the evidence is based only on a small trial. Mirtazapine is not used widely in apnea treatment.

Apnea also leads to memory problems. For a long time doctors thought the decline in short term memory ability was due to sleep deprivation. New findings indicate the apnea actually causes shrinkage in areas of the brain important to memory. Use of CPAP machines and regular exercise seems to help.

Scientific Papers:

Epidemiology

It is estimated that sleep apnea affects 100 million people worldwide. Approximately 80 percent of those people are currently undiagnosed. This is most probably due to mild and ambiguous symptoms (in less severe cases) that neither the patients or doctors attribute to apnea.

Prevalence in the United States

According to a 2009 study, seven percent of Americans suffer from sleep apnea. Adults make up most of the sufferers, with nearly 20 percent of adult males and nine percent of adult females afflicted with some form of the disease at some time in their lives. Moderate-to-severe apnea affects nine percent of males and four percent of females. Two percent of children are also affected by sleep apnea, most of these children being infants under one year of age. Another source (Medicinenet.com) says 4% of men and 2% of women have OSA and refers to a study showing apnea develops in 1.5% of adults every year. The federal government estimates only a quarter of those with obstructive apnea sought medical evaluation in the 2005-2008 period.

Changes in Prevalence

Apnea has been on the rise in the United States, partly because of better diagnosis and partly because of increased obesity rates. In the early 90’s, approximately 3 percent of the general population had apnea. In 2002, a study printed in the “American Journal of Respiratory and Critical Care Medicine” found that number had risen to five percent. A 2009 survey found the percentage had increased again by two percent. This shows us that sleep apnea has increased more than twofold in a little under twenty years. The increase in apnea is directly correlated with the rise in obesity within the United States although increased awareness and better diagnosis is part of it, too. The government’s Healthy People initiative claims that 25.5% of Americans with the symptoms of OSA seek medical attention.

Differences in Populace Based on Age, Race, and Gender

Sleep apnea is most prevalent in middle-aged males. Males are between two and three times as likely to develop apnea than women. This appears to be due, at least in part, to physiological and anatomical differences between the genders. Males typically have a larger neck circumference and a longer pharyngeal airway, which make them more susceptible to sleep apnea. Males also have a higher apneic threshold, due to certain male hormones, according to a study done by Safwan Badr in 2005 (Reference 4).

There are also differences between ethnic groups. African Americans are more than twice as likely to get apnea than Caucasians. This difference has been found to be caused by genetic factors and is independent of other respiratory or weight-related illnesses, says the American Lung Association. Pacific Islanders and Hispanics also develop sleep apnea at a higher rate, though it appears to be due to increased obesity rates in those ethnic groups. Prevalence in Asians is similar to that in Caucasians, but the causation is different. In Asians, sleep apnea more often develops due to faciocranial features and is not associated with obesity.

The incidence of obstructive sleep apnea goes up with age and is most commonly seen in people between the ages of 40 and 60. Curiously, after age 60, incidence goes down. People in their 70s have only twice the incidence of 20-year-olds. Children sometimes have apnea, although it is more rare than in adults. Children born with facial deformities can get apnea. Childhood apnea is often solved by removing the tonsils.

At Risk Groups

Pregnant women, smokers and those suffering from obesity have higher rates of apnea.

A staggering 78 percent of pregnant women experienced symptoms indicative of sleep apnea at some point in their pregnancy, most of them in the third trimester. This seems to be due to a combination if enlarged blood vessels, effects of hormonal changes on the body, and weight gain.

Smokers face an elevated risk. They are three times as likely to develop apnea as nonsmokers. The increase is the result of
increased upper airway inflammation and fluid retention, both of which are caused by smoking. The increased risk, however, is temporary, and goes away once a smoker quits smoking.

The biggest correlate of sleep apnea is obesity. Moderate to severe sleep apnea can be found in 40 percent of obese individuals and 70 percent of sleep apnea sufferers are medically defined as obese. There is no solid evidence as to why obesity has such a profound effect on apnea, but a variety of factors are theorized to come in to play. Research indicates increased hormones found in obese individuals negatively impact chemoreflex, while increased weight and fat deposits affect airway anatomy and function.

Antioxidants and Sleep Apnea and Other Disorders

Scientists have found that the punctuated breathing in apnea imposes oxidative stress on the body, and that antioxidants in the diet can actually improve sleep quality. (Although a recent Polish study concluded otherwise.)

Experiments where animals were forced to experience intermittent hypoxia (to simulate apnea) found the animals suffer problems in memory and learning, and that at a cellular level these animals have more reactive oxygen species floating around.  This oxidative stress leads to tissue damage, inflammation, and apoptotic neuronal cell death.  Treatment with antioxidants might help protect brain cells. The evidence is unclear. We don’t mean to hedge, but when it comes to antioxidants and antioxidant supplements science has yet to find definitive answers about so much.

In any case, what is the person with apnea to do?

Researchers at the University of Louisville reviewed the effects of the antioxidant compounds, known as polyphenols, found in green tea and concluded that drinking several cups of green tea each day may help to ward of cognitive problems and memory loss in people who have the sleep disorder.

More specifically they concluded catechin polyphenols may relieve neurobehavioral deficits  caused by intermittent hypoxia.

This was concluded from animal experiments, but if you scale up the regimens used it is the equivalent of a human drinking six to 10 cups of green tea each day.  Rats that were given green tea-infused water to drink consistently and significantly outperformed their plain water counterparts on tests of memory and spatial learning.

In recent years, there has been a considerable amount of research conducted on green tea and some even claim it can slow the progression of memory decline experienced in Alzheimer’s patients.

Another study of N-acetylcysteine supplements found they may have the potential to help apnea patients fend off damage from apnea-induced oxidants.

Waking imposes an oxidative stress on the brain and part of the “housekeeping” function of sleep is repair and protection against this stress.  Prolonged sleep deprivation activates an adaptive stress pathway that the body uses to protect against oxidative compounds. The body therefore acts as its own anti-oxidant producer. This pathway is similar to the processes the body uses to protect itself against neurodegenerative diseases.

Does this mean you should take antioxidant supplements to help you sleep?  Experts aren’t ready to go that far, but it is safe to say a healthy diet rich in fruits and vegetables can help maintain overall health.There is also evidence that eating anti-oxidant rich kiwi fruit can help improve sleep quality.

And of course melatonin, the neurohormone so important in the
regulation of the sleep cycle, acts as an antioxidant in the body.

References:

  • Foster, B., 2008, Uncovering Sleep Apnea Misconceptions, The Nurse Practitioner, 33(6):23-28
  • Pagel, J., 2008, The Burden of Obstructive Sleep Apnea and Associated Excessive Sleepiness, The Journal of Family Practice, 57(8):S3-S7
    Ballard, R., 2008, Management of Patients With Obstructive Sleep Apnea, The Journal of Family Practice, 57(8):S24-S30
  • Riha, R., Diefenbach, K., Jennum, P., McNicholas, W., 2008, Genetic Aspects of Hypertension and Metabolic Disease in the Obstructive Sleep Apnoea-Hypoponea, Sleep Medicine, 12:49-63
  • Smith, I., Lasserson, T., Wright, J., 2006, Drug Therapy for Obstructive Sleep Apnea in Adults, Cochrane Database of Systematic Reviews, Issue 3
  • Black, J. and Hirshkowitz, M., 2005, Modafinil for Treatment of Residual Excessive Sleepiness in Nasal Continuous Positive Airway Pressure-Treated Obstructive Sleep Apnea/Hypopnea Syndrome, 28(4):464-471
  • “Epidemiology in Obstructive Sleep Apnea Syndrome”; Current Opinion
    in Pulmonary Medicine; November, 1995
  • “Epidemiology of Obstructive Sleep Apnea: A Population Health
    Perspective”; American Journal of Respiratory and Critical Care
    Medicine; 200
  • Infant & Children Sleep Apnea Awareness Foundation: Awareness –
    http://www.kidssleepdisorders.org/awareness.html#adults
  • “Gender Differences in Sleep Apnea”; RT-For Decision Makers in
    Resiratory Care; Safwan Badr, MD; June, 2005
  • American Lung Association; Obstructive Sleep Apnea or
    Sleep-Disordered Breathing –
    http://www.lungusa.org/assets/documents/publications/solddc-chapters/osa.pdf
  • “Epidemiology, Risk Factors, and Consequences of Obstructive Sleep
    Apnea and Short Sleep Duration”; Progress in Cardiovascular Diseases;
    Nabil M. Al Lawati, Sanjay R. Patel, Najib T. Ayas; June, 2009
  • Shift Work Disorder News: Global Sleep Apnea Diagnostic and
    Therapeutic Devices Market Projected to Reach US$5.8 Billion by 2015,
    According to New Report by Global Industry Analysts –
    http://www.shiftworkdisorder.com/global-sleep-apnea-diagnostic-and-therapeutic-devices-market-projected-to-reach-us5-8-billion-by-2015-according-to-new-report-by-global-industry-analysts-101601.html
  • “Effects of Age on Sleep Apnea in Men”; American Journal of
    Respiratory and Critical Care Medicine; Edward O. Bixler, Alexandros
    N. Vgontzas, Thomas Ten Have, Kathy Tyson, and Anthony Kales; January,
    2005
  • National Sleep Foundation: Pregnancy and Sleep –
    http://www.sleepfoundation.org/article/sleep-topics/pregnancy-and-sleep
  • Baby Center: Sleep Problems: Sleep Apnea –
    http://www.babycenter.com/0_sleep-problem-sleep-apnea_7547.bc”
  • Obesity, Sleep Apnea, and Hypertension”; Hypertension; Robert
    Wolk; Abu S.M. Shamsuzzaman; Virend K. Somers; November 2003
  • Mayo Clinic: Sleep Apnea: Risk Factors –
    http://www.mayoclinic.com/health/sleep-apnea/DS00148/DSECTION=risk-factors
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