Letters to the Editor

Do Long-Acting Beta2 Agonists Impair the Effect of Short-Acting Beta2 Agonists in Some Patients?

Am Fam Physician. 2011 Nov 15;84(10):1080-1085.

Original Article: Medical Therapy for Asthma: Updates from the NAEPP Guidelines

Issue Date: November 15, 2010

Available at: http://www.aafp.org/afp/2010/1115/p1242.html

to the editor: In this update on asthma therapy, Drs. Elward and Pollart write: “In general, the effectiveness of short-acting beta2 agonists is not impaired in regular users of long-acting beta2 agonists.” The citation for this statement is a study published in 1993 involving 12 patients with mild asthma.1 A subsequent study found that use of salmeterol (Serevent) blunted the bronchodilator response to salbutamol (available as albuterol in the United States).2 In 2006, Drs. Weinberger and Abu-Hasan described two adolescent boys with life-threatening asthma exacerbations in whom response to albuterol and control of symptoms improved after withdrawal of salmeterol therapy.3 As Drs. Elward and Pollart note, the Salmeterol Multicenter Asthma Research Trial found an increase in severe asthma exacerbations and asthma-related deaths among patients randomized to salmeterol therapy.4

Long-acting beta2 agonists have documented benefits in controlling symptoms and reducing exacerbations when used as add-on therapy in patients whose symptoms are not adequately controlled with inhaled steroids alone.5 However, there is evidence that these agents blunt the bronchodilator response in some patients. Therefore, before prescribing these agents, it is important to educate patients on the optimal use of inhaled steroids and document the persistence of symptoms despite an adequate trial of inhaled steroids.

Author disclosure: No relevant financial affiliations to disclose.

REFERENCES

1. Smyth ET, Pavord ID, Wong CS, Wisniewski AF, Williams J, Tattersfield AE. Interaction and dose equivalence of salbutamol and salmeterol in patients with asthma. BMJ. 1993;306(6877):543–545.

2. Grove A, Lipworth BJ. Bronchodilator subsensitivity to salbutamol after after twice daily salmeterol in asthmatic patients. Lancet. 1995;346(8969):201–206.

3. Weinberger M, Abu-Hasan M. Life-threatening asthma during treatment with salmeterol. N Engl J Med. 2006;355(8):852–853.

4. 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(5):1393]. Chest. 2006;129(1):15–26.

5. Greenstone IR, Ni Chroinin MN, Masse V, et al. Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. Cochrane Database Syst Rev. 2005;(4):CD005533.

in reply: Dr. Edwards addresses an important issue in optimal asthma management. We agree that long-acting beta2 agonists should be used with caution and never in isolation. As we discussed in our article, before prescribing these agents physicians need to educate patients on optimal use and reasons for treatment. The Salmeterol Multicenter Asthma Research Trial, poorly designed as it was, clearly suggested the risk of using long-acting beta2 agonists in isolation.1 There are conflicting data on the safety of long-acting beta2 agonists, but overall the literature, including an updated Cochrane review, demonstrates consistent and clinically important benefits when using these agents in combination with inhaled steroids.24

The U.S. Food and Drug Administration has conducted a comprehensive review of the benefits and risks of using long-acting beta2 agonists to treat asthma. Based on this review, it recommended that long-acting beta2 agonists be reserved for patients whose asthma cannot be managed adequately with an asthma controller medication such as an inhaled steroid, and that long-term use of long-acting beta2 agonists be limited to patients who require prolonged use of these drugs.5

The risk of serious asthma exacerbations and asthma-related death is not limited to long-acting beta2 agonists. Most physicians are well aware that short-acting beta2 agonists can worsen asthma and cause asthma-related death. This could be because of increased sensitivity to bronchoconstrictive stimuli or masking of the symptoms of worsening asthma. Therefore, current asthma treatment guidelines also recommend that albuterol and other short-acting beta2 agonists be used only as needed for short-term symptom relief and emphasize that asthma controller medications be used to minimize short-acting beta2 agonist use.6 Panel for the Expert Panel Report 3. Dr. Pollart has no relevant financial affiliations to disclose.

Author disclosure: Dr. Elward serves on the National Asthma Education and Prevention Program Coordinating Committee and its select Guidelines Implementation

REFERENCES

1. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM; SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual phar-macotherapy for asthma or usual pharmacotherapy plus salmeterol [published correction appears in Chest. 2006;129(5):1393]. Chest. 2006;129(1):15–26.

2. Kramer JM. Balancing the benefits and risks of inhaled long-acting beta-agonists–the influence of values. N Engl J Med. 2009;360(16):1592–1595.

3. Drazen JM, O'Byrne PM. Risks of long-acting beta-agonists in achieving asthma control. N Engl J Med. 2009;360(16):1671–1672.

4. Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. Cochrane Database Syst Rev. 2010;(4):CD005533.

5. Chowdhury BA, Dal Pan G. The FDA and safe use of long-acting beta-agonists in the treatment of asthma. N Engl J Med. 2010;362(13):1169–1171.

6. National Asthma Education and Prevention Program. Expert panel report 3: guidelines for the diagnosis and management of asthma. Bethesda, Md.: National Heart, Lung, and Blood Institute; August 2007. NIH publication no. 07-4051.

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