Long-Term Relief Medications

These medications are taken on a regular basis to prevent asthma attacks and control chronic symptoms.

Inhaled Corticosteroids

Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (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:

  • Inhaled steroids include fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer drugs are more powerful than the older generation of inhaled drugs. Budesonide (Pulmicort Respules) is available in a jet nebulizer for children from 12 months to 8 years. It is the first such medication to be approved for children in this age group.
  • The FDA approved a new inhaled corticosteroid, mometasone furoate (Asmanex) was approved in 2005 for patients age 12 and older.
  • 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 (QVAR, Autohaler) to deliver the drugs 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 may include:

  • 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 not common with inhalators.
  • Some children experience changes in mood, memory, and behavior. These changes are not permanent.
  • Some studies have suggested a higher risk for gum inflammation.
  • Oral steroids reduce bone density. Research now reports that inhaled steroids -- both older and newer drugs -- also may affect bone growth and density. However, a number of studies report only a slight effect (about half an inch) 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 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 drugs, 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.) Sudden changes in consciousness may suggest low blood sugar, 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 drugs, 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.

For now, experts 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. However, researchers are continuing to investigate the safety and effectiveness of inhaled corticosteroid use in young children. A small 2005 study found that fluticasone, used twice daily for 6 months, improved lung function and clinical outcomes in children younger than 2 years. A retrospective review of combined inhaled corticosteroid/long-acting beta2-agonist treatment in children younger than 5 years concluded that combination therapy is safe and effective for this age group.

Long-Acting Beta2-Agonists

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 drugs 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 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.

Long-acting forms are not used alone on any regular 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. 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 age 4 years and older. This inhaler appears to be safe and possibly more effective that either drug used alone for patients who do not respond well to other treatments.

Studies indicate that these are safe for children and may 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 drugs.

Specific Warning on Salmeterol and Formoterol. In 2003 a "black box" warning was added to product packaging for drugs that contain salmeterol, including Serevent Diskus, and Advair Diskus. Serevent and Advair are approved for patients age 12 years and older. The warning was based on a study that demonstrated more serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo.

In 2006, the FDA updated the warning to include formoterol (Foradil Aerolizer, approved for patients 5 years and older). Warnings for salmeterol and formoterol products emphasize that these medicines can increase the risk of severe asthma episodes. Long-acting beta2-agonists require 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. The FDA recommends that patients:

  • Use long-acting beta2-agonists only if other medicines (such as steroids) have not helped control asthma
  • Use a short-acting bronchodilator, not a long-acting beta2-agonist, to treat sudden wheezing
  • Do not use long-acting beta2-agonists to treat wheezing that is getting worse. Call your doctor if this situation occurs
  • Do not stop using any asthma medicines without first talking to your doctor

Cromolyn and Similar Drugs

Cromolyn sodium (Intal) is 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 drug 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 needs to be taken only 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. Patients should not use it for self-medication without the advice of a doctor.

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 or leukotriene modifiers) are oral medications that block leukotrienes. Leukotrienes are 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 drugs, leukotrienes are used for prevention and not for treating acute asthma attacks.

Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving helpful for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID) -induced asthma. However, most studies to date have reported better success with inhaled corticosteroids than with the leukotriene-antagonists. A 2006 study of children with mild-to-moderate persistent asthma indicated that the corticosteroid fluticasone worked better than the leukotriene-antagonist montelukast in controlling symptoms. Nevertheless, some studies suggest that montelukast, which comes in a chewable tablet, may be particularly useful for managing asthma in small children (ages two to five), since they have trouble with inhaled steroids.

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 drugs 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 leukotriene-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.

Theophylline

Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) is a mild to moderate bronchodilator that has been used to treat childhood asthma for more than 30 years. It is useful for treating nocturnal asthma and may also have anti-inflammatory qualities even in low doses.

Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can therefore be taken once or twice a day with good results.

Side effects may include changes in behavior, mood, and memory. If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.

The risks for these adverse effects are small if the drug is taken exactly as prescribed but the following precautions should be noted:

  • Infants tend to metabolize the drug extremely slowly and, therefore, should receive very low doses.
  • By the time children reach age 1, however, they metabolize the drug faster than adults. There is a risk, therefore, of toxic effects.
  • Fever and certain antibiotics may slow down the rate at which theophylline is eliminated from the body. In such cases, the doctor may want to reduce the dosage of theophylline.

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.

Omalizumab

Omalizumab (Xolair) is now FDA approved for patients age 12 and older who have moderate to severe persistent allergic asthma. The first drug of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), or a genetically developed drug 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 2 to 4 weeks. Because of its high cost, the drug is 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). A 2005 review of omalizumab clinical trials found that omalizumab reduced the rate of asthma worsening by 38% and reduced the total rate of emergency visits by 47%.

[For more information on medications, see In-Depth Report #04: Asthma in adults.]