The U.S. National Asthma Education and Prevention Program (NAEPP) guidelines for the diagnosis and management of asthma recommend
Symptoms of asthma include:
The word asthma comes from an ancient Greek word meaning panting. Essentially, asthma is an inflammatory lung condition that makes it difficult to breathe properly.
When people inhale, the air travels through the following body structures:
Asthma is a chronic condition in which these airways undergo changes that are usually triggered by allergens, other environmental triggers, or by infection. Such changes appear to be two specific responses:
These actions in the airways cause coughing, wheezing, and shortness of breath (dyspnea), the classic symptoms of asthma.
In the hyperreactive response, smooth muscles in the airways constrict and narrow excessively in response to inhaled allergens or other irritants. This sudden contraction in the muscle walls of the bronchioles is called a bronchospasm.
Bronchospasms can result from many different health conditions (allergies, bronchitis, and chronic obstructive pulmonary disease) but asthma is the most common cause.Everyone's airways constrict when exposed to allergens or irritants, but there are major differences in the hyperreactive response that occurs in people with asthma:
The hyperreactive stage is followed by the inflammatory response, which generally contributes to asthma in the following way:
Inflammation appears to be present in the lungs of all patients with asthma, even those with mild cases, and plays a key role in all forms of the disease.
Doctors don’t fully understand the causes of asthma. They believe the disorder is most likely caused by a combination of genetic (inherited) factors and environmental triggers (such as allergens and infections). Asthma tends to run in families. Children whose parents have asthma are more likely to develop it themselves.
Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70 - 85% of children with asthma also have allergies. While only a small percentage of children with allergies have asthma, some of these children may develop asthma as adults. .
In people with allergies, the immune system overreacts to exposure to allergens. Allergic asthma is triggered by inhaling certain substances (allergens), such as:
An asthma attack can be triggered or aggravated by direct irritants to the lungs. Studies indicate that the more indoor allergens to which a child is allergic, the higher the child's risk for severe asthma. Important irritants include:
The role of early childhood respiratory and intestinal infections is very complex. Viral respiratory infections certainly worsen existing asthma, but the most common ones are unlikely to cause childhood asthma. In fact, early respiratory and intestinal infections may offer some protection against asthma. The “hygiene hypothesis” theorizes that early exposure to dirt, germs, and certain infections may help stimulate the immune system to help prevent childhood asthma.
Studies suggest that most respiratory infections are not important causes of asthma in children, except in certain cases. An important exception is the respiratory syncytial virus (RSV), which is associated with the development of asthma. RSV is the major viral cause of infant pneumonia. Studies also indicate that infants who have reduced lung function within a few days after birth are at increased risk of developing asthma by the time they are 10 years old.
Common respiratory infection viruses that cause colds (such as the rhinovirus) may be associated with the development of asthma in some people. More likely, these viruses do not directly cause asthma, but they worsen asthma in children who already have it. Rhinovirus is the most common infection associated with asthma attacks.
Research indicates that children who have viral-induced wheezing during infancy may be at increased risk for later development of asthma. However, many children outgrow attacks of intermittent wheezing.
Asthma affects about 7 million American children. Asthma has dramatically increased over the past few decades in both developed and developing countries around the world. It is now the most common chronic childhood illness.
Most children develop asthma symptoms before they are 5 years old.
Among younger children, asthma is twice as common in boys as in girls, but after puberty it is more common in girls.
African-American children have significantly higher rates of asthma than Caucasian children. Hispanic children are also at higher risk. Both groups of minority children are more likely to have fatal asthma than Caucasian children. Ethnicity and genetics are, however, less likely to play a role in these differences than socioeconomic factors, such as having less access to optimal health care and a greater likelihood of living in an urban area (another risk factor for asthma). Caucasian children who live in cities also face a higher risk for asthma.
Certain pregnancy and perinatal factors may possibly be associated with increased risk for asthma, although none are very well studied or proven. Results from studies include:
There is a strong association between obesity and asthma. People who are overweight (body mass index greater than 25) also have more difficulty getting their asthma under control. Weight loss in anyone who is obese and has asthma or shortness of breath helps reduce airway obstruction and improve lung function.
Patients with asthma often also have gastroesophageal reflux disease (GERD), which is associated with acid reflux. It is not entirely clear which condition causes the other or whether they are both due to common factors. Acid reflux can worsen asthma symptoms. Treating GERD may help improve asthma in some patients.
Aspirin-induced asthma (AIA) is a condition in which asthma gets worse after taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). AIA often develops after a viral infection. It is a particularly severe asthmatic condition, associated with many asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.
Patients with aspirin-induced asthma (AIA) should avoid aspirin and other NSAIDs, including ibuprofen (Advil and other brands, generic) and naproxen (Aleve, generic). Some research indicates that acetaminophen (Tylenol, generic) may also trigger or worsen asthma, particularly in children. Although this link is not yet proven, parents whose children have asthma should be alert for this possible effect.
Asthma is the third leading cause of hospitalization in children under age 15. The condition can be very serious in children, particularly those younger than age 5, because their airways are very narrow.
Asthma death rates have steadily declined, and asthma is now only rarely fatal in children. Even low mortality numbers are unacceptable, however, since asthma deaths are largely preventable.
Factors associated with an increased risk of death from asthma in children include:
African-American children have more than six times the death rate of Caucasians in the age groups of 4 years and younger and 15 - 24 years. Hispanic children also have a higher risk.
Asthma generally improves as children get older, although most school-age children with persistent asthma will still experience symptoms through adolescence. Some children outgrow their asthma by adulthood. In general, the more severe the childhood asthma, the greater the likelihood that it will persist.
Severe asthma can cause long-lasting damage and possibly permanent scarring in some patients. The risk for such injury is highest when asthma strikes children in their first 3 - 5 years. There does not appear to be any significant risk for long-term lung damage for children who develop mild-to-moderate persistent asthma between ages 5 - 12. Children adapt well to living with asthma, and even with severe asthma they can function as well as healthy children in virtually all areas of life.
In children with asthmatic symptoms, it is important to first consider as a possible cause inhaled foreign objects such as peanuts; viral infections such as croup; and bacterial infections, which may be accompanied by high fever and progress rapidly. Any child who has frequent coughing or respiratory infections should be checked for asthma.
The classic symptoms of an asthma attack include:
Any of these symptoms may worsen with exercise, viral infections, exposure to irritants, stress, or changes in weather.
The end of an attack is often marked by a cough that produces thick, stringy mucus. After an initial acute attack, inflammation lasts for days to weeks, often without symptoms. (The inflammation itself must still be treated, however, because it usually causes relapse.)
The following signs and symptoms may indicate a life-threatening situation:
Asthma often progresses very slowly, but it may sometimes develop to a fatal or near-fatal attack within a few minutes. It is very difficult to predict when an attack will become very serious. Any symptoms that suggest a serious attack should be immediately treated with a rescue bronchodilator. If symptoms persist, call for emergency help.
Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath. This condition generally occurs in children and young adults, most often during intense exercise in cold dry air. Symptoms are generally most intense about 10 minutes after exercising, then gradually resolve.
EIA is triggered only by exercise and is distinct from ordinary allergic asthma in that it does not produce a long period of airway hyperactivity, as allergic asthma does. (However, some people have both forms of asthma.) People who have only EIA do not need long-term maintenance therapy.
Many patients experience a worsening of their asthma symptoms during the nighttime, especially during sleep. Attacks often occur between 2 and 4 a.m. Factors that increase the risk for nocturnal asthma include allergen exposure, sinus problems, GERD, chronic obstructive lung diseases, and the sleep-disordered breathing associated with obstructive sleep apnea.
Your child’s doctor will want to know any patterns or triggers associated with asthma symptoms. Be sure to let the doctor know:
If symptoms and a patient's history strongly suggest asthma, the doctor will usually perform lung (pulmonary) function tests to confirm the diagnosis and determine the severity of the disease.
A standard test uses a spirometer, an instrument that measures the amount of air taken into and exhaled out from the lungs. The patient breathes into a tube that is connected into a machine. The spirometer can give several measures of airflow::
If the airways are obstructed, these measurements will fall. Depending on the results, the doctor will take the following steps:
The doctor may recommend skin or blood allergy tests, particularly if a specific allergen is suspected. Allergy skin tests may help diagnose allergic asthma, although they are not recommended for people with year-round asthma.
A stepwise approach is recommended for treating asthma. Medications and dosages are increased when needed, and decreased when possible. Based on a patient’s age and asthma severity, there are specific recommendations regarding whether to use long-term control medications and which ones to use. Patient education, environmental control measures, and management of any other conditions are also included.
In choosing therapy, doctors also consider a patient's risk for more severe exacerbations. Contributing factors include parental history of asthma, atopic dermatitis, and known sensitivity to different allergens or foods. Patients should be reevaluated within 2 - 6 weeks of starting therapy to assess response.
While medications play an essential role in the management of asthma, appropriate management of asthma also involves:
Doctors classify asthma based on factors such as symptom frequency, nighttime awakenings, lung function, medication need, and normal activity functioning. Asthma severity is generally classified into four groups:
Once asthma severity is classified, there is a recommended treatment approach that takes into consideration three age groupings:
Key points regarding recommendations for children 4 years old and younger include:
Key points regarding recommendations for children 5 years and older include:
The variation between age groups consists mostly of which medications are recommended and how soon to start various medications and treatments.
Medications for asthma fall into two categories:
The goal of asthma therapy is to maximize long-term control of the illness with medications and other treatment approaches, thereby minimizing the frequency of asthma symptoms and asthma attacks. Parents can greatly reduce the frequency and severity of their children’s asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time.
Unfortunately, many patients do not understand the difference between medications that provide rapid, short-term relief and those that are used for long-term symptom control. It is important not to overuse short-term rescue medications or underuse long-term control corticosteroid medications. .
These are the signs of well-controlled asthma:
Most asthma drugs are inhaled. The basic devices used for inhalation are the metered-dose inhaler (MDI), dry powder inhalers, and nebulizers.
Metered-Dose Inhaler. The standard device for administering asthma medication is the metered-dose inhaler (MDI). The medicine comes in a pressurized canister, which is placed inside a plastic inhaler. MDIs, particularly when used with a spacer, allows precise doses to be delivered directly to the lungs.
The spacer is a tube that is attached to the inhaler. It serves as a holding chamber for the medication that is sprayed by the inhaler. The spacer makes it easier and more efficient for the medication to reach the lungs. For children who are too young to breathe into the tube, a face mask can be attached to the spacer.
Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2-agonists or corticosteroids directly into the lungs. Unlike an MDI, dry powder inhalers do not contain a propellant and do not require a spacer. Some patients find that they are more difficult to manage than MDIs. Humidity or extreme temperatures can affect DPIs' performance, so they should not be stored in humid places (bathroom cabinets) or locations subject to high temperatures (glove compartments during summer months).
Dry-powder may cause tooth erosion. Children should rinse their mouths out with a fluoride mouthwash right after using these inhalers.
Nebulizers. A nebulizer is a machine that delivers a fine spray of medication-containing liquid. Nebulizers are often used for children younger than 3 years and sometimes for older children who have difficulty using the MDI. It takes 5 - 10 minutes to administer medication using a nebulizer. Because the spray is less targeted than with the inhaler, it must deliver large amounts of the drug. This increases the risk for toxicity and severe side effects. In general, children who can.
Quick-relief (rescue) medications work immediately to relax airways and quickly control acute asthma attacks. They are not useful for preventing attacks or controlling inflammation in the airways.
The standard quick-relief medication is a beta2-agonist inhaler. Beta2-agonists serve as bronchodilators, relaxing and opening constricted airways during an acute asthma attack. A short-acting inhaled beta2-agonist, taken as needed, is often the only medication used by children with chronic mild asthma.
Albuterol (Proventil, Ventolin), called salbutamol outside the U.S., is the standard short-acting beta2-agonist in the United States.
Short-acting bronchodilators are usually administered through inhalation and are effective for 3 - 6 hours. They relieve the symptoms of acute attacks, but they do not control the underlying inflammation. If asthma continues to worsen with the use of these drugs, a doctor may prescribe corticosteroids or other drugs to treat underlying inflammation.
Side Effects of Beta2-Agonists. Side effects of all beta2-agonists may include:
Loss of Effectiveness and Overdose. Short-acting beta2-agonists become less effective when taken regularly over time, which increases the risk for overuse. Overdose can be serious and in rare cases even life threatening.
Two inhaled drugs, ipratropium bromide (Atrovent) and tiotropium (Spiriva), act as bronchodilators over time. Neither is highly beneficial for acute asthma attacks. Moreover, the drugs are not approved specifically for asthma. Some parents, however, report these drugs are helpful for treating wheezing in infants. The drugs are also sometimes used in the emergency room to treat children with severe asthma to enhance the effects of intravenous beta2-agonists.
Common oral corticosteroids include prednisone/prednisolone, dexamethasone, methylprednisolone, and hydrocortisone. They reduce inflammation very effectively. They are most commonly prescribed for asthma flare-ups that do not respond to inhaler medications. Doctors may provide a written prescription for patients to keep on hand, with specific instructions about when to fill it. Usually, the dosage starts out higher and is gradually reduced over a 5 - 7 day period. Prolonged use of oral steroids has widespread and sometimes serious side effects, so they are not generally given to children for longer than 5 - 7 days.
Asthmanefrin is an over-the-counter (non-prescription) rescue bronchodilator that contains a form of epinephrine called racepinephrine. The medication is inhaled through an atomizer. Asthmanefrin came on the market in 2012 as a replacement for Primatene Mist. (Primatene Mist was discontinued because its inhaler used chloroflurocarbon (CFC) propellant. CFCs are banned because of environmental concerns.) Asthmanefrin does not use CFC and is approved for patients ages 4 years and older. However, many doctors have safety concerns regarding the use of epinephrine products for asthma. In particular, this medication can be risky if overused. In general, patients are much better off seeing a healthcare provider and using inhalers that are prescribed.
Long-term control (maintenance) medications are taken on a regular basis to prevent asthma attacks, control inflammation in the airways, and manage chronic symptoms.
Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (they do not relax the airways) and have little immediate effect on symptoms. Instead, they work over time to reduce inflammation and prevent permanent injury in the lungs. They can also help prevent asthma attacks from occurring.
Taking a corticosteroid drug through an inhaler makes it possible to provide effective local anti inflammatory activity in the lungs with very few side effects elsewhere in the body. (By contrast, oral steroids have considerable side effects throughout the body.) Inhaled corticosteroids are recommended as the primary therapy for any patient needing long-term control medications for persistent asthma.
Examples of inhaled corticosteroids:
Inhaled corticosteroids are the preferred first-line therapy for children with asthma. However, doctors caution against corticosteroids for infants and toddlers with mild asthma and urge close monitoring, especially for children under age 5 with severe asthma who are receiving high doses.
Inhaled corticosteroids and growth in children is a common concern. However, a number of studies report only a slight effect (about half an inch) on children's growth, which may be only temporary. These growth changes are mostly when higher doses are being used. Poorly controlled asthma can also affect growth.
Side effects of inhaled steroids may include:
Long-acting beta2-agonists (LABAs) are used for preventing an asthma attack (not for treating attack symptoms). These drugs should never be used alone in the treatment of asthma in adults or children. They can be dangerous when used alone, because they can mask asthma symptoms, and they can increase the risk of asthma death unless paired with an inhaled steroid. LABAs should only be used in combination with an asthma controller medication, such as an inhaled corticosteroid. LABAs should be used for the shortest time possible, and should only be used by patients whose asthma is not adequately controlled by asthma controller medications.
Salmeterol-fluticasone (Advair), formoterol-budesonide (Symbicort), and mometasone-formoterol (Dulera) are long-acting beta2 agonists products combined with a steroid in a single inhaler that are used for treatment of moderate-to-severe asthma. Advair is approved for children ages 4 years and older, and Symbicort and Dulera are approved for children ages 12 years and older.
Leukotriene antagonists (also called anti-leukotrienes or leukotriene modifiers) are oral medications used for prevention, NOT for treating acute asthma attacks.
Leukotriene antagonists include montelukast (Singulair, generic), zafirlukast (Accolate, generic), and zileuton (Zyflo). These drugs are considered an alternative for long-term control of asthma. Other potential uses include preventing exercise-induced asthma.
Side Effects and Complications. Upset stomach, headache, and sore throat are the most common side effects of leukotriene antagonists. Because these drugs can raise liver enzyme levels, patients may need periodic liver tests.
Leukotriene antagonists may cause mental health and behavioral changes. Mood problems include agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, tremor, and suicidal thinking. Patients who take a leukotriene antagonist drug should be monitored for signs of behavioral and mood changes. Doctors should consider discontinuing the drug if patients exhibit any of these symptoms.
Omalizumab (Xolair) is FDA-approved for patients age 12 and older. It should be considered only for children over 12 years who have moderate-to-severe persistent asthma related to allergies and for adults who have severe asthma and allergies. Omalizumab is a biologic drug that targets and blocks the antibody immunoglobulin E (IgE), a chemical trigger of the inflammatory events associated with an allergic asthma attack.
Omalizumab is given by injection every 2 - 4 weeks. It is used only to treat patients whose symptoms are not controlled by inhaled corticosteroids.
Side Effects and Complications. About 1 in 1,000 patients who take omalizumab develop anaphylaxis (a life-threatening allergic reaction). Patients can develop anaphylaxis after any dose of omalizumab, even if they had no reaction to a first dose. Anaphylaxis may occur up to 24 hours after the dose is given.
Omalizumab should always be injected in a doctor’s office and health care providers should observe patients for at least 2 hours after an injection. Patients should also carry emergency self-treatment for anaphylaxis (such as an Epi-Pen) and know how to use it. With an Epi-Pen, or similar auto-injector device, patients can quickly give themselves a life-saving dose of epinephrine.
Anaphylaxis symptoms include:
The FDA is currently reviewing whether omalizumab may be associated with increased risk for heart and vascular problems (ischemic heart disease, arrhythmias, cardiomyopathy, heart failure, pulmonary hypertension, and blood clots).
Theophylline relaxes the muscles around the bronchioles and also stimulates breathing. Since the introduction of inhaled corticosteroids and long-acting beta2-agonists, theophylline is not used as often for asthma treatment. It may still be used in some circumstances, such as for treating nocturnal asthma. Theophylline is available in tablet, liquid, and injectable forms. Theophylline should not be used by people with peptic ulcers or GERD, and should be used with caution by anyone with heart disease, liver disease, high blood pressure, or seizure disorders.
If a child is taking theophylline on an ongoing basis, the doctor should monitor the drug level at the start of therapy and at regular intervals thereafter.
Children older than 6 months should receive an influenza vaccination every year. All children should receive pneumococcal vaccination. The pneumococcal conjugate vaccination (PCV13) is recommended for children younger than 5 years old. Children age 2 years and older who are at high risk for pneumococcal disease should also get the pneumococcal polysaccharide vaccine (PPSV23). .
Patients with asthma and chronic allergic rhinitis may need daily medications. Patients with severe seasonal allergies may need to start taking medications a few weeks before the pollen season, and to continue them until the season is over.
Immunotherapy ("allergy shots") may help reduce asthma symptoms, and the use of asthma medications, in patients with known allergies. They may also help prevent the development of asthma in children with allergies. Immunotherapy poses some risk for severe allergic reactions, especially for children with poorly controlled asthma, so it is important that the doctor carefully evaluates the child’s asthma condition.
Researchers are studying an oral form of immunotherapy that uses a sublingual (under-the-tongue) tablet. Recent studies indicate that sublingual therapy may be helpful for asthma in particular, and may also be beneficial for allergic rhinitis. However, many questions remain including dosage and duration of treatment. At this time, sublingual immunotherapy is not considered standard practice in the United States.
Respiratory infections, including the common cold, can interact with allergies to worsen asthma. People with asthma should try to minimize their risk for respiratory tract infections. Using alcohol-based hand rubs and washing hands are simple but effective preventive measures. Vaccines are also very important for prevention.
Children with obvious symptoms of reflux (heartburn) or children who have difficulty managing asthma may consider the following lifestyle changes:
Many people with asthma turn to alternative therapies including high-dose vitamins, homeopathic remedies, probiotics, and herbal supplements. There is no evidence that any of these treatments are helpful for asthma.
However, because stress can worsen asthma symptoms and make breathing more difficult, alternative therapies that focus on relaxation and stress reduction may be helpful. These modalities include:
The more allergies a child has, the more severe the asthma. Making lifestyle changes to reduce allergy attacks and other triggers is extremely important.
Asthma action plans create a written document for patients and parents to manage asthma during stable times and to more easily identify when asthma is worsening. Important components of a home program include:
A peak flow meter is a handheld plastic device for measuring peak expiratory flow rate (PEFR). PEFR measures how fast you can expel air out of your lungs and is an indication of lung functioning. Changes in the PEFR may indicate problems with asthma control even before symptoms appear. If your child’s PEFR is lower than normal, it may mean that rescue medications are needed.
It is a good idea to keep a written record of your child’s peak flow meter readings. This data can help the doctor adjust medications and recognize problems before they become serious.
To use a peak flow meter, set the meter to zero and have your child stand or sit upright, take a deep breath and exhale hard and fast into the meter. Write down the number that appears on the meter.
House dust is a reservoir for pollen and dust mites. It is important to control household allergens and pollutants in the home.
Controlling for Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particular Air (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. In fact, vacuuming stirs up both mites and cat allergens. If possible, avoid carpets and rugs.
Controlling Pets. For children who have an existing allergy to pets:
Bedding, Curtains, and Bedroom Environment.
Exterminating Pests (Cockroaches and Mice).
Reducing Humidity in the House. Living in a damp environment is counterproductive. Humidity levels should not exceed 30 - 50%.
Preventing Exposure to Cigarette and Cooking Smoke. Parents who smoke are strongly urged to quit. Studies indicate that exposure to second-hand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children. Even smoky cooking can worsen asthma.
Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:
Parents should make sure that their child’s school has a copy of the written asthma action plan. The plan should contain a list of medications the child takes (including which ones need to be taken during school hours), identified asthma triggers, and emergency contact numbers. Parents should also make sure that the school staff is trained in the steps to take in case of an asthma attack.
Asthma is no reason to avoid exercise. Historically, about 10% of Olympic athletes have asthma. Some studies indicate that long-term exercise may help control asthma and reduce hospitalization. Exercise can help control weight, which can help with asthma symptoms.
Encourage children with asthma to swim and play sports, such as baseball, that will be less difficult for them. Intense activities lasting less than 2 minutes, such as sprinting or competitive swimming, may cause fewer problems than longer-lasting exercises.
Young people who enjoy running should probably choose an indoor track to avoid pollutants. Swimming is excellent for people with asthma. Yoga, which uses stretching, breathing, and meditation techniques, may also have particular benefits.
Patients should consult their doctors before starting any exercise program. Exercise-induced asthma (EIA) is a limited condition that has specific recommendations.
Hints for Reducing Exercise-Induced Asthma (EIA). EIA occurs only after exercise and is more likely to occur with regular paced activities in cold, dry air. The following are some suggestions for reducing its impact:
Asthma can trigger a difficult emotional-physical cycle:
Caregivers must first focus on reducing their own anxiety, which can heighten a child's own fears. The next step is to help the child relax. One method for this is as follows:
This exercise both relaxes the child and discourages shallow, oxygen-poor breathing. Massaging the child in gentle circles on the chest is relaxing and may also loosen mucus.
Other recommendations to provide relief include:
Home visits by a nurse or other healthcare provider may be helpful if your family is having trouble managing your child's asthma or following prescribed treatments. It is also a good idea to have your home evaluated for allergic triggers.
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Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Bethanne Black, and the A.D.A.M. Editorial team.