Safety of Long-Acting β-Agonists
Authors: Shelley R. Salpeter
Journal: Annals of Internal Medicine (2006)

Letters7 November 2006Safety of Long-Acting β-AgonistsShelley R. Salpeter, MDShelley R. Salpeter, MDFrom Santa Clara Valley Medical Center, San Jose, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-9-200611070-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE: My coauthors and I appreciate the thoughtful comments on our meta-analysis. We would first like to clarify that our analysis included only randomized, placebo-controlled trials to assess the safety of LABAs compared with placebo. The results showed that LABA use in these trials increased asthma hospitalizations, life-threatening attacks, and asthma deaths by 2- to 4-fold compared with placebo.In response to Dr. Ernst and colleagues' commentary elsewhere in this issue (1), we chose trials of at least 3 months' duration to allow adverse effects associated with continued treatment to develop. Long-acting β-agonists have an initial beneficial effect on ...References1. Ernst P, McIvor A, Ducharme FM, Boulet LP, FitzGerald M, Chapman KR, et al. Safety and effectiveness of long-acting inhaled β-agonist bronchodilators when taken with inhaled corticosteroids. Ann Intern Med. 2006;145:692-4. LinkGoogle Scholar2. Bensch G, Berger WE, Blokhin BM, Socolovsky AL, Thomson MH, Till MD, et al. One-year efficacy and safety of inhaled formoterol dry powder in children with persistent asthma. Ann Allergy Asthma Immunol. 2002;89:180-90. [PMID: 12197575] CrossrefMedlineGoogle Scholar3. Busse W, Levine B, Andriano K, Lavecchia C, Yegen U. Efficacy, tolerability, and effect on asthma-related quality of life of formoterol bid via multidose dry powder inhaler and albuterol QID via metered dose inhaler in patients with persistent asthma: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. Clin Ther. 2004;26:1587-98. [PMID: 15598475] MedlineGoogle Scholar4. D'Urzo AD, Chapman KR, Cartier A, Hargreave FE, Fitzgerald M, Tesarowski D. Effectiveness and safety of salmeterol in nonspecialist practice settings. Chest. 2001;119:714-9. [PMID: 11243947] CrossrefMedlineGoogle Scholar5. Price D, Dutchman D, Mawson A, Bodalia B, Duggan S, Todd P, et al. Early asthma control and maintenance with eformoterol following reduction of inhaled corticosteroid dose. Thorax. 2002;57:791-8. [PMID: 12200524] CrossrefMedlineGoogle Scholar6. Steffensen I, Faurschou P, Riska H, Rostrup J, Wegener T. Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol. Allergy. 1995;50:657-63. [PMID: 7503401] CrossrefMedlineGoogle Scholar7. Taylor DR, Town GI, Herbison GP, Boothman-Burrell D, Flannery EM, Hancox B, et al. Asthma control during long-term treatment with regular inhaled salbutamol and salmeterol. Thorax. 1998;53:744-52. [PMID: 10319056] CrossrefMedlineGoogle Scholar8. Von Berg A, Papageorgiou Saxoni F, Wille S, Carrillo T, Kattamis C, Helms PJ. Efficacy and tolerability of formoterol Turbuhaler in children. Int J Clin Pract. 2003;57:852-6. [PMID: 14712884] MedlineGoogle Scholar9. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26. [PMID: 16424409] CrossrefMedlineGoogle Scholar10. Pauwels RA, Löfdahl CG, Postma DS, Tattersfield AE, O'Byrne P, Barnes PJ, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997;337:1405-11. [PMID: 9358137] CrossrefMedlineGoogle Scholar11. Woolcock A, Lundback B, Ringdal N, Jacques LA. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med. 1996;153:1481-8. [PMID: 8630590] CrossrefMedlineGoogle Scholar12. Greenstone IR, Ni Chroinin MN, Masse V, Danish A, Magdalinos H, Zhang X, 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;:CD005533. [PMID: 16235409] MedlineGoogle Scholar13. Ni Chroinin M, Greenstone IR, Danish A, Magdolinos H, Masse V, Zhang X, et al. Long-acting beta2-agonists versus placebo in addition to inhaled corticosteroids in children and adults with chronic asthma. Cochrane Database Syst Rev. 2005;:CD005535. [PMID: 16235410] MedlineGoogle Scholar14. Boulet LP, Cartier A, Milot J, Côté J, Malo JL, Laviolette M. Tolerance to the protective effects of salmeterol on methacholine-induced bronchoconstriction: influence of inhaled corticosteroids. Eur Respir J. 1998;11:1091-7. [PMID: 9648961] CrossrefMedlineGoogle Scholar15. Hancox RJ, Aldridge RE, Cowan JO, Flannery EM, Herbison GP, McLachlan CR, et al. Tolerance to beta-agonists during acute bronchoconstriction. Eur Respir J. 1999;14:283-7. [PMID: 10515402] CrossrefMedlineGoogle Scholar16. Salpeter SR, Ormiston TM, Salpeter EE. Meta-analysis: respiratory tolerance to regular beta2-agonist use in patients with asthma. Ann Intern Med. 2004;140:802-13. [PMID: 15148067] LinkGoogle Scholar17. Patterns of Medication Use in the United States 2004: A Report from the Slone Survey. Boston: Slone Epidemiology Center at Boston University; 2004. Google Scholar18. The World Factbook: United States. Washington, DC: Central Intelligence Agency; 2005. Google Scholar19. National Asthma Education and Prevention Program program description. Bethesda, MD: National Heart, Lung, and Blood Institute. Accessed at www.nhlbi.nih.gov/about/naepp/naep_pd.htm on 20 September 2006. Google Scholar20. Sly RM. Decreases in Hispanic and non-Hispanic asthma mortality. Ann Allergy Asthma Immunol. 2006;96:76-9. [PMID: 16440536] CrossrefMedlineGoogle Scholar21. Lawson JA, Senthilselvan A. Asthma epidemiology: has the crisis passed? Curr Opin Pulm Med. 2005;11:79-84. [PMID: 15591893] CrossrefMedlineGoogle Scholar22. Hussey PS, Anderson GF, Osborn R, Feek C, McLaughlin V, Millar J, et al. How does the quality of care compare in five countries? Health Aff (Millwood). 2004;23:89-99. [PMID: 15160806] CrossrefMedlineGoogle Scholar23. Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, et al. The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med. 1992;326:501-6. [PMID: 1346340] CrossrefMedlineGoogle Scholar24. Lanes SF, García Rodríguez LA, Huerta C. Respiratory medications and risk of asthma death. Thorax. 2002;57:683-6. [PMID: 12149527] CrossrefMedlineGoogle Scholar25. Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005;60:740-6. [PMID: 16055613] CrossrefMedlineGoogle Scholar26. Teale C, Morrison JF, Muers MF, Pearson SB. Response to nebulized ipratropium bromide and terbutaline in acute severe asthma. Respir Med. 1992;86:215-8. [PMID: 1535717] CrossrefMedlineGoogle Scholar27. Summers QA, Tarala RA. Nebulized ipratropium in the treatment of acute asthma. Chest. 1990;97:425-9. [PMID: 2137076] CrossrefMedlineGoogle Scholar28. Donohue JF. Therapeutic responses in asthma and COPD. Bronchodilators. Chest. 2004;126:125S-137S; discussion 159S-161S. [PMID: 15302773] Google Scholar29. Gross NJ. Anticholinergic agents in asthma and COPD. Eur J Pharmacol. 2006;533:36-9. [PMID: 16488410] CrossrefMedlineGoogle Scholar30. Westby M, Benson M, Gibson P. Anticholinergic agents for chronic asthma in adults. Cochrane Database Syst Rev. 2004;:CD003269. [PMID: 15266477] MedlineGoogle Scholar31. Currie GP, Lee DK, Srivastava P. Long-acting bronchodilator or leukotriene modifier as add-on therapy to inhaled corticosteroids in persistent asthma? Chest. 2005;128:2954-62. [PMID: 16236972] CrossrefMedlineGoogle Scholar32. Ram FS, Cates CJ, Ducharme FM. Long-acting beta2-agonists versus anti-leukotrienes as add-on therapy to inhaled corticosteroids for chronic asthma. Cochrane Database Syst Rev. 2005;:CD003137. [PMID: 15674901] MedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Shelley R. Salpeter, MDAffiliations: From Santa Clara Valley Medical Center, San Jose, California.Disclosures: Dr. Salpeter has consulted on legal cases involving β-agonists but has never given expert testimony and has no contracts with law firms. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-Analysis: Effect of Long-Acting β-Agonists on Severe Asthma Exacerbations and Asthma-Related Deaths Shelley R. Salpeter , Nicholas S. Buckley , Thomas M. Ormiston , and Edwin E. Salpeter Safety of Long-Acting β-Agonists Graeme P. Currie Safety of Long-Acting β-Agonists Stuart W. Stoloff Safety of Long-Acting β-Agonists Dermot Ryan Safety of Long-Acting β-Agonists Mats Jacob Lindberg Safety of Long-Acting β-Agonists Harold S. Nelson and Paul M. Dorinsky Safety and Effectiveness of Long-Acting Inhaled β-Agonist Bronchodilators When Taken with Inhaled Corticosteroids Pierre Ernst , Andrew McIvor , Francine M. Ducharme , Louis-Philippe Boulet , Mark FitzGerald , Kenneth R. Chapman , and Tony Bai , for the Canadian Asthma Guideline Group Metrics Cited byThe risk of asthma mortality with inhaled long acting β-agonistsCurrent awareness: Pharmacoepidemiology and drug safety 7 November 2006Volume 145, Issue 9Page: 708-710KeywordsAsthmaCorticosteroid therapyDeath ratesEvidence based medicineHealth careHospitalizationsSafetyStatistical dataTreatment guidelines ePublished: 7 November 2006 Issue Published: 7 November 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...