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Asthma in Children and Adolescents
Description: An in-depth report on how asthma is diagnosed, treated, and managed in children.
Prevention
Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (that is, they do not relax the airways) and have little effect on symptoms. Instead, they work over time to reduce inflammation and prevent permanent injury in the lungs. Many studies have now shown that the use of inhaled corticosteroids in patients with moderate to severe asthma significantly reduce the rate of rehospitalizations and deaths from asthma. Nevertheless, they are still significantly underprescribed in the patients who need them most.
Inhaled Corticosteroids. Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (Oral steroids have considerable side effects.) They are currently recommended as the primary therapy under the following circumstances:
For any asthmatic condition more serious than occasional episodes of mild asthma. (Low-doses of inhaled steroids may even be safe and effective for some people with mild asthma, particularly those who find themselves using beta2-agonists daily.)
When treatment with bronchodilators is not effective.
Examples of inhaled corticosteroids are the following (not all are available to children):
The most recent generation of inhaled steroids include (in order of potency) fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer agents, are more powerful than the older generation of inhaled agents. Budesonide (Pulmicort Respules) is available in a jet nebulizer for children from 12 months to 8 years. It is, in fact, the first such medication to be approved for children in this age group.
The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhalers that use very fine sprays (e.g., QVAR, Autohaler) deliver the agents deep into the lungs may prove to be as effective as the newer, more potent steroids.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are now available.
Evidence strongly suggests that early treatment with corticosteroids is important for children with severe asthma to prevent deterioration in lung function.
Side effects of inhaled steroids are the following:
- The most common side effects are throat irritation, hoarseness, and dry mouth. These effects can be minimized or prevented by using a spacer device and rinsing the mouth after each treatment.
- Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible but are not common with inhalators.
- Some children experience changes in mood, memory, and behavior. They are not are not permanent.
- Some studies have suggested a higher risk for gum inflammation.
- It is well known that oral steroids reduce bone density and research now reports that inhaled steroids--both older and newer agents--also may affect bone growth and density. Of some comfort are a number of studies reporting only a slightly less (about half an inch) effect on children's growth, which may be only temporary. It is still unknown if these drugs have any significant long-term effect on bone density. Calcium supplements appear to help prevent bone loss due to inhaled steroids.
- It is not yet known, however, whether inhaled steroids affect lung growth in very young children. Steroids administered using nebulizers are of particular concern.
- There is also some concern that the more potent agents, particularly fluticasone, suppress the adrenal system to a greater degree than other steroid inhalants. This effect in turn reduces levels of natural steroids--notably cortisol, the major stress hormone. (This is a serious side effect of oral steroids.) Of note, sudden changes in consciousness may suggest hypoglycemia, which can occur with adrenal insufficiency and was reported in a few children taking high doses of fluticasone. A 2002 study also observed abnormally lower morning levels of cortisol in children taking fluticasone.
Because the newer potent agents, particularly fluticasone, may produce major side effects similar to oral steroids, it is important to aim for the lowest effective dose possible. Fortunately, some studies suggest that low doses of fluticasone may achieve the same benefits as with high ones, thus reducing risks for serious side effects. Better delivery methods may also allow lower doses. For example, an encouraging 2002 study suggested that administering lower doses of beclomethasone using an Autohaler, which delivers the drug in an extra-fine spray, were as effective as higher doses delivered with an MDI. At this time experts caution against corticosteroids for infants and toddlers with mild asthma and urge close monitoring especially for children under five with severe asthma who are receiving high doses.
Oral Corticosteroids. Oral agents are usually the last drugs to be added to an asthma treatment program and the first to be removed. Common oral corticosteroids include prednisone/prednisolone, dexamethasone, methylprednisolone, and hydrocortisone. They reduce inflammation very effectively, but children generally take them only for five days after hospitalization for an acute attack. Compliance among children can be low, however, since these agents have a bitter taste and can cause vomiting. Taking oral dexamethasone for two days may be as effective and more tolerable than the standard a five-day regimen of prednisone/prednisolone. Prolonged use of oral steroids has widespread and sometimes serious side effects, and so they are not generally give to children for longer than a few days.
Long-Acting Beta2-Agonists and Corticosteroid Combinations
Long-acting beta2-agonists, including salmeterol (Serevent) and formoterol (Foradil) plus inhaled corticosteroids are now the preferred preventive treatment for adults and children with moderate to severe asthma. Long-acting beta2-agonists are used for preventing an asthma attack (not for treating symptoms). The effects of one dose of a long-acting beta2-agonist last for about 12 hours, so they are particularly effective during the night. These agents also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.
In comparison studies, salmeterol and formoterol appear to be equally beneficial. Formoterol has a much faster action, however, and may achieve better control of nighttime asthma. Formoterol, in fact, works almost as fast as the short-acting albuterol and is sometimes used to treat asthma symptoms. Salmeterol should never be used for treatment of acute episodes. For this purpose, short-acting bronchodilators should be used. (Formoterol has a faster action and may, in some cases, be used for treating symptoms, but patients should check with their physician.)
Long-acting forms are not used alone on any regular on basis, since they may reduce the effectiveness of the short-acting beta2-agonists (the mainstays for treating acute attacks). In patients with moderate to severe asthma, the long-acting beta2 agonists are best used in combination with anti-inflammatory drugs. In fact, unlike short-acting forms, these beta2-agonists may even have anti-inflammatory properties. A single inhaler (Advair Diskus) that combines both long-acting beta2-agonists and corticosteroids is now available for children over age 12. This inhaler appears to be safe and possibly more effective that either agent used alone for patients who do not respond well to other treatments.
Studies indicate that these are safe for children and may, in fact, be particularly effective for them. In one year-long study of children with mild to moderate asthma, salmeterol was not as effective as the corticosteroid beclomethasone, but it did reduce asthma symptoms without retarding growth.
Side Effects. Side effects of long-acting beta2-agonists are similar to the short-acting agents.
Specific Warning on Salmeterol. In 2003 a black box warning was added to product packaging for drugs that contain salmeterol, including Serevent Inhalation Aerosol, Serevent Diskus, and Advair Diskus. The warning urges caution based on a 2003 study that demonstrated a higher incidence of serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo. Salmeterol requires up to 20 minutes to achieve effectiveness, and there is a danger of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. (Overdose has been fatal only in rare cases.) The risk for serious asthma episodes with salmeterol appears to be highest in African-American and elderly patients with severe asthma.
Salmeterol should never be used for stopping an attack. Patients should NOT stop taking salmeterol as long-acting treatment without first talking to their physician.
Cromolyn and Similar Drugs
Cromolyn sodium (Intal) serves as both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Cromolyn has been the anti-inflammatory agent of choice for prevention of asthma attacks in children over four with chronic moderate asthma. It is not as effective as inhaled corticosteroids, however, for reducing hospitalization rates, improving symptoms, and reducing the use of beta beta2-agonists in children with persistent asthma. Still, cromolyn has a well-known long-term safety record, while the long-term adverse effects of corticosteroids in children are still not fully known. Many children who need asthma maintenance therapy will still do well on cromolyn. (It may not provide any real benefit for children under four.)
Nedocromil (Tilade) is similar to cromolyn and only needs to be taken once a day. It also prevents asthmatic reactions to cold and exercise. It is not used in very young children. A cromolyn nasal spray called Nasalcrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Asthmatic patients should not use it for self-medication without the advice of a physician.
Side Effects. Side effects of cromolyn include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. Nedocromil has an unpleasant taste and some people have complained of nausea, headache, and spasms in the airways, but no serious side effects have been reported.
Leukotriene-Antagonists
Leukotriene-antagonists (also called anti-leukotrienes) are oral medications that block leukotrienes, powerful immune system factors that, in excess, produce a battery of damaging chemicals that can cause inflammation and spasms in the airways of people with asthma. As with other anti-inflammatory agents, leukotrienes are used for prevention and not for treating acute asthma attacks.
The leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These agents are proving to be effective for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID)-induced asthma. Unfortunately, most studies to date are still reporting better success with inhaled corticosteroids than with the leukotriene-antagonists. Their anti-inflammatory actions are different from those of steroids, however, and combinations of the two agents are being tried. A 2002 analysis of 13 studies, however, reported only modest benefits when anti-leukotrienes were added to corticosteroids. The combination did improve asthma control in some of the studies, but they did no reduce corticosteroid use. (In all but one of these studies the subjects were adults. It is not clear if these results are applicable to children.)
Nevertheless, studies suggest that montelukast, which comes in a chewable tablet, may be particularly useful for managing asthma in small children (ages two to five) with asthma, since they have trouble with inhaled steroids. As suggested by another 2000 study on the effects of zafirlukast, they may also reduce the severity of cat allergies, regardless of whether or not asthma is also present.
Side Effects and Complications. Gastrointestinal distress is the most common side effect of leukotriene-antagonists. Very few other side effects have been reported. In general, these agents appear to be safe and well tolerated.
Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. In fact, usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotrienes-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.
Other concerns are indications of liver injury in patients taking zileuton and zafirlukast when taken at higher than standard doses. No adverse effects on the liver have been reported to date with montelukast.
Xolair
Omalizumab (Xolair) is now FDA approved for patients age 12 and older who have moderate to severe persistent allergic asthma. The first agent of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), or a genetically developed agent designed to attack very specific targets.
Omalizumab prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies have shown excellent benefits of the drug, including a reduced need for corticosteroids, fewer hospitalizations, and significant symptomatic improvements. Because IgE may play an important role in causing childhood asthma, omalizumab may prove to be even more helpful for children than adults; further study is underway.
Omalizumab is administered by injection every two to four weeks. Because of its high cost, it is presently being reserved for patients with severe asthma and whose symptoms are difficult to control even with corticosteroids. Experts predict that the applications of this therapy will likely expand in time, however, because it is a powerful modifier of severe seasonal and food allergies (in patients with or without asthma).