Beta2 Agonists in the Treatment of Asthma
Am Fam Physician. 2006 Jul 15;74(2):232.
The alert by the U.S. Food and Drug Administration (FDA) on use of long-acting beta2 agonists for the treatment of asthma1 has made headlines since it was issued on November 18, 2005. The advisory suggests that these agents should be reserved for patients whose asthma is not controlled with low or moderate doses of inhaled corticosteroids. The focal points of this advisory are the findings of the Salmeterol Multicenter Asthma Research Trial,2 which was stopped because of a small but significant number of asthma-related deaths, and similar data from studies of formoterol (Foradil Aerolizer) that showed a possible increase in severe asthma exacerbations.
On November 21, 2005, the FDA issued suggested language for patient information3 for salmeterol (Serevent), fluticasone propionate plus salmeterol (Advair), and formoterol. The essence of the message for patients and physicians is that inhaled corticosteroids should be used first, and long-acting beta2 agonists should be added if low or moderate doses of corticosteroids are insufficient.
As family physicians, we see a large number of patients with asthma for whom we must prescribe the safest and most effective treatment, using inhaled corticosteroids and, when required, corticosteroids plus long-acting beta2 agonists. For those with severe asthma or asthma that cannot be controlled with low or moderate doses of inhaled corticosteroids, the low risk associated with long-acting beta2 agonists is likely less than the risk of death from uncontrolled asthma. For patients with less severe asthma, it is appropriate to begin methodically, using short-acting beta2-agonists alone for patients with intermittent asthma and adding anti-inflammatory or controller medications for those with persistent asthma. Inhaled corticosteroids are the most effective anti-inflammatory medications for asthma; the OPTIMA trial (Oxis and Pulmicort Turbuhaler In the Management of patients with Asthma)4 showed that more than 70 percent of mild or moderate, persistent asthma can be controlled with inhaled corticosteroids alone, with results equivalent to treatment with a combination of inhaled corticosteroids and long-acting beta2 agonists.
Asthma therapy should follow the model of all step-up therapy, using a single agent first and then following the patient and individualizing treatment as needed. For management of persistent asthma, physicians should begin with inhaled corticosteroids, substituting a leukotriene modifier for patients with mild asthma who refuse corticosteroid therapy. If rapid bronchodilation is needed during the initiation period, a short-acting beta2-agonist can be used three or four times per day while the inhaled corticosteroid reaches peak activity.5 After the initiation period, monotherapy with the corticosteroid should continue; the short-acting beta2 agonist may be used for occasional symptom exacerbations. In patients with moderate asthma, moderate doses of inhaled corticosteroids may be used before switching to combination therapy. In patients with severe asthma, combination therapy is required.
Individualizing therapy means that physicians and their patients must communicate effectively.6 Patients should answer a set of simple questions about disease severity, daytime symptoms, nocturnal awakenings, the need to miss or modify activities, the use of rescue bronchodilators, and exacerbations. These data can provide an important basis for modifying treatment.
BARBARA YAWN, M.D., M.SC., is director of research at the Olmsted Medical Center and adjunct professor of family medicine at the University of Minnesota Medical School, Rochester.
Address correspondence to Barbara Yawn, M.D., M.Sc., 826 19th St. NE, Rochester, MN 55906-4247 (e-mail: email@example.com). Reprints are not available from the author.
1. U.S. Food and Drug Administration. FDA public health advisory: Serevent Diskus (salmeterol xinafoate inhalation powder), Advair Diskus (fluticasone propionate and salmeterol inhalation powder), Foradil Aerolizer (formoterol fumarate inhalation powder). Accessed June 22, 2006, at: http://www.fda.gov/cder/drug/advisory/LABA.htm.
2. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM, SMART Study Group . The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol [Published correction appears in Chest 2006;129:1393]. Chest. 2006;129:15–26.
3. U.S. Food and Drug Administration. Serevent Diskus, Advair Diskus, and Foradil Information (long acting beta agonists). Accessed June 22, 2006, at: http://www.fda.gov/cder/drug/infopage/LABA/default.htm.
4. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, Runnerstrom E, Sandstrom T, Svensson K, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med. 2001;164(8 pt 1):1392–7.
5. Williams SG, Schmidt DK, Redd SC, Storms W. Key clinical activities for quality asthma care: recommendations of the National Asthma Education and Prevention Program. MMWR Recomm Rep. 2003;52(RR-6):1–8.
6. Yawn BP, Fryer GE, Lanier D. Asthma severity: the patient’s perspective. J Asthma. 2004;41:623–30.
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