Asthma Medications: New Guidelines Improve Safety

Asthma is a chronic lung condition that commonly starts in childhood and often continues into adulthood. People with asthma have episodes when their air passages become narrow from inflammation, excess mucous production, and tightening of the muscles in the airway walls. This makes breathing more difficult and causes coughing and wheezing. The air passages of asthmatics are unusually sensitive to certain triggers such as pollen, dust, animal dander, smoke, and others. Exposure to triggers makes their airways overreact leading to asthma symptoms. There has been considerable research into the treatment of asthma and there are a number of effective medications which allow people with asthma to live normal, active lives.

Recently, the US Food and Drug Administration (FDA) has issued a new set of guidelines regarding LABA drugs in response to the results of several large-scale studies of LABA safety.

Asthma medications are generally divided into two categories: rescue medications that provide quick relief when an attack has started, and controller medications that help to decrease the frequency and severity of asthma flare-ups by decreasing chronic airway inflammation and hyperreactivity. If a person has only occasional attacks, and is completely free of symptoms between attacks, a rescue medication may be all that is necessary. But a person who needs "rescuing" several times a week, or has chronic symptoms such as cough or poor tolerance of exercise, a daily controlling medication may be in order. Asthma treatment is most effective when carefully tailored to meet the individual patient's needs. This requires collaboration between doctor and patient that includes conscientious use of prescribed medications and accurate reporting of asthma symptoms.

One group of asthma mediations is called the short-acting beta agonists (SABAs). These drugs act by helping the muscles in the air passages of the lungs to relax and re-expand. They do not reverse the inflammation or decrease the excess mucus. The most commonly prescribed SABA is albuterol, which is usually delivered directly into the lungs with a hand held inhaler, or a nebulizer machine, which turns liquid medication into a fine mist. SABAs act quickly to help stop the vicious cycle of symptoms as early as possible in the attack but they do not address inflammation or prevent future attacks.

Another class of beta agonist, called long-acting beta agonists (LABAs) also relaxes constricted airway muscles, but this class of medication does not act quickly enough to be effective rescue medications. One LABA is salmeterol, which is also delivered to the lungs by an inhaler and has been used as a daily treatment to help achieve long-term control. Currently, long-acting beta agonists are available as solo drugs, or in combination inhalers with steroids.

Recently, the US Food and Drug Administration (FDA) has issued a new set of guidelines regarding LABA drugs in response to the results of several large-scale studies of LABA safety.(1) They are critically important for anyone with asthma to know about.

Why has the FDA become concerned about daily use of LABAs?

The concern about the long-term beta agonists arose because studies showed that patients who used LABAs actually had a higher risk of worsening of their asthma symptoms so severely that they might lead to hospitalization and even death.

• One study, referred to as the SMART study, (Salmeterol Multicenter Asthma Research Trial) evaluated the asthma experiences of about 25,000 patients between 1996-2003.(2) During the study period, patients who were 12 years and older were given standard asthma therapy plus either daily salmeterol (a LABA) or a placebo for a 28- week period. Investigators kept track of each patient's asthma symptoms, flare-ups, hospitalizations, and severe asthma episodes. They found that there were small, but statistically significant increases in asthma-related deaths or asthma related life-threatening experiences in the population receiving salmeterol.
• In 2008, the FDA reviewed 110 studies evaluating the use of LABA in a total of 60,954 patients with asthma. This analysis also suggested an increased risk for asthma exacerbations in patients using LABAs compared to asthmatic patient s who didn't use them. They found the biggest risk in children ages 4-11 years old(1)

Why would an asthma drug make asthma worse?

Researchers aren't sure. One of the possibilities that has been raised is that there are genetic differences among people which affect their responses to beta agonists, making them work less effectively in some people than others.(2) Another is that regular use of the long-acting version of the beta agonist actually decreases the airways' responsiveness to the short-acting beta agonists so they don't work as well when they are needed in the rescue mode. This hypothesis was explored in a study that summarized the results of 22 trials of short and long-term beta agonist use. They found that regular beta agonist use for at least 1 week in patients with asthma results in tolerance to the drug's airway relaxing effect.(3) This would make it harder for patients who developed an asthma flare-up to calm the attack with their rescue inhaler, and their symptoms could get progressively worse.

What are the new FDA guidelines?

1. Long acting beta agonists should only be used for a long-term in patients whose asthma is not controlled on standard asthma controller medications. Commonly used controllers include inhaled steroids, singulair, cromolyn, and theophylline.
2. If needed, they should be used only as long as it takes to achieve adequate control of asthma symptoms. Once control is achieved, the long acting beta agonist should be discontinued and the patient should continue on their standard controller medications
3. When they are used, long acting beta agonists should not be used alone. They should always be used together with a controller medication.
   
   When a pediatric or adolescent patient requires both a long acting beta agonist and inhaled steroid, their physician should prescribe one of the inhalers that contains both medications, so the child or teen is more likely to get both the necessary drugs into their system as often as prescribed.
4. Long acting beta agonists should never be used as rescue medications.

Is it safe to use the long acting beta agonist as long as I use it with a controller?

Thus far, there have not been enough studies to determine whether the risk posed by using long acting beta agonists decreases if they are used along with inhaled steroids. Similarly, the combination inhalers that contain both drugs have not been adequately studied. That's why the FDA is recommending that even when LABAs are used with a controller medication, they are used for as short a time as possible to achieve the desired asthma control.

More information about asthma and its treatment can be found at:

http://www.aafa.org/ Asthma and Allergy Foundation website
http://www.cdc.gov/ASTHMA/ Centers for Disease Control website
http://www.nlm.nih.gov/medlineplus/asthma.html The National Library of Medicine and National Institute of Health website