Asthma in Adults

Description

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:

• 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. Experts have some concern, then, that these potent agents, particularly fluticasone, may produce major side effects similar to oral agents. Studies are now suggesting, however, that the same benefits can be achieved with low doses of fluticasone as with high doses, thus reducing risks for serious side effects. (Of note, budesonide has been given a pregnancy approval rating.)
• 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 inhaler systems, such as QVAR, which uses extra fine formulations of beclomethasone to allow deep delivery into the lungs, may prove to be as effective as the newer, more potent steroids. Beclomethasone is believed to be safe during pregnancy.
• Inhalers that combine both long-acting beta2-agonists and corticosteroids are now available.

Inhaled corticosteroids must be taken regularly. It may take a month to perceive their effects and up to a year to achieve full benefits. Some of these agents may have some immediate benefits. In one study, inhaled budesonide reduced inflammation in the airways within six hours.

Optimal timing of the dose is important and may vary depending on the medication. Most of the newer inhaled steroids and even some older ones are now available as a single daily dose, which some patients may respond to.

Inhaled steroids are generally considered safe and effective and only rarely cause any of the more serious side effects reported with prolonged use of oral steroids. 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.
• A 2001 study, however, reported a higher risk for cataracts in patients over age 40. (No higher risk was observed in younger people.)
• Some studies are reporting a higher risk for bone loss in patients who take inhaled steroids regularly, which is known to occur with oral steroids. (A number of bone-preserving medications are now available that might safely offset this effect.) Medications are available to help prevent bone loss.
• There is some concern that the more potent agents, particularly fluticasone, suppress the adrenal system (which secretes natural steroids) to a greater degree than other steroid inhalants. (This is a serious side effect of oral steroids.)

Of note, during pregnancy, inhaled budesonide and beclomethasone are considered to be generally safe.

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, methylprednisolone, and hydrocortisone. They very effectively reduce inflammation but are generally used only after hospitalization for an acute attack. In some severe cases, they may be used as maintenance.

Adverse effects of prolonged use of oral steroids include cataracts, glaucoma, osteoporosis, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and psychosis. Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, bisphosphonates, or hormone replacement therapy in post-menopausal women. Vitamin C and E may help reduce the risk of cataracts.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. It should be noted that there have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a physician first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their physician measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Long-Acting Beta2-Agonists and Corticosteroid Combinations

Long-acting beta2-agonists, including salmeterol (Serevent) or 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.

Single devices that contain both agents are now available in the U.S. (Advair) and parts of Europe (Seretide, Symbicort). These inhalers appear to be safe and possibly more effective than either agent used alone for patients who do not respond well to other agents.

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. Nedocromil (Tilade) is similar to cromolyn. 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.

Candidates. Cromolyn is often used in children with allergic asthma, but it has also been an important treatment for exercise-induced asthma (EIA) in all age groups, for pregnant women, and possibly for preventing allergic asthma in adults as well as children. Both cromolyn and nedocromil appear to be useful for patients with aspirin-induced asthma. These agents do not effectively treat asthma once an attack is underway. They also have very little long-term benefits on lung function compared to inhaled corticosteroids.

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 not reduce corticosteroid use. (In all but one of these studies the subjects were adults.)

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).