HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Full Text Free Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Cloosterman, S. G. M. Articles by van Schayck, C. P. Search for Related Content PubMed PubMed Citation Articles by Cloosterman, S. G. M. Articles by van Schayck, C. P.

A Placebo-Controlled Clinical Trial of Regular Monotherapy With Short-Acting and Long-Acting ß₂-Agonists in Allergic Asthmatic Patients^*

^* From the Department of General Practice and Social Medicine (Drs. Cloosterman, Bijl-Hofland, and Akkermans), University of Nijmegen, and Department of Pulmonology (Drs. van Herwaarden and Folgering), Medical Centre Dekkerswald, University of Nijmegen, Nijmegen; the Department of Pulmonology (Dr. Elshout), Rijnstate Hospital, Arnhem; and University of Maastricht (Dr. van Schayck), Maastricht, The Netherlands.

Correspondence to: Sonja G. M. Cloosterman, MSc, PhD, Department of General Practice and Social Medicine, 229, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands; e-mail: S.Cloosterman{at}hsv.kun.nl

Background: Some recent studies suggest that regular ß₂-agonist use may result in inadequate control of asthma. It has been hypothesized that this occurs particularly in allergic asthmatic patients exposed to relevant allergens. Moreover, it is still unclear whether this occurs during the use of both short-acting and long-acting ß₂-agonists.

Methods: Asthmatic patients (n = 145) allergic to house dust mite (HDM) were randomly allocated to monotherapy with a short-acting ß₂-agonist (SA; n = 48), a long-acting ß₂-agonist (LA; n = 50), or placebo (n = 47), double blind, double dummy. The study covered three periods: (1) a 4-week run-in period, in which no changes took place; followed by (2) cessation of treatment with asthma medication including inhaled corticosteroids, introduction of allergen avoidance measures (active/placebo treatment) to lower HDM exposure in the active group, and an 8-week washout period to adjust patients to these changes; followed by (3) a 12-week study medication period. At the start of the 12-week medication period, and every 4 weeks thereafter, spirometric measurements (FEV₁ and provocative concentration of histamine causing a 20% fall in FEV₁ [PC₂₀]) were performed. Peak flow and asthma symptoms were recorded daily. Additionally, at the start and every 6 weeks thereafter, dust samples were collected from mattresses and living room and bedroom floors to assess HDM (der p 1) concentrations. Effects on FEV₁, PC₂₀, peak flow, and asthma symptoms were analyzed with repeated-measurement analysis and corrected for the exposure to HDM allergens.

Results: There were no significant differences among the three medication groups after 12 weeks for FEV₁. However, a significant decrease in mean FEV₁ percent predicted (95% confidence interval [CI]) was observed within the SA group: - 6.6 (- 10.4 to - 2.8) (p = 0.0002). A decrease in geometric mean PC₂₀ (95% CI) of - 1.2 (- 1.96 to - 0.44) doubling concentration was observed within the SA group (p = 0.05). No significant changes in FEV₁ and PC₂₀ were observed > 12 weeks within the LA group or the placebo group. There were neither changes in peak flow and asthma symptom scores among the three medication groups nor within the groups. Moreover, none of the parameters showed interactive effects with allergen exposure.

Conclusion: There were no significant differences among the three medication groups for FEV₁ and PC₂₀. The within-treatment group comparison showed a significant small decline in FEV₁ for the SA group (but not for the LA group), which could indicate that monotherapy with SAs might have negative effects on FEV₁. This was not seen during regular use of LAs. No clear pathophysiologic mechanism can explain these findings at the moment. Relatively high or low exposure to allergens did not alter these findings.

Key Words: allergens • allergic asthma • ß₂-agonists • bronchial hyperresponsiveness • tolerance

This article has been cited by other articles:

				S. R. Salpeter, N. S. Buckley, T. M. Ormiston, and E. E. Salpeter Meta-Analysis: Effect of Long-Acting {beta}-Agonists on Severe Asthma Exacerbations and Asthma-Related Deaths Ann Intern Med, June 20, 2006; 144(12): 904 - 912. [Abstract] [Full Text] [PDF]

				H W. Kelly What Is New with the {beta}2-Agonists: Issues in the Management of Asthma Ann. Pharmacother., May 1, 2005; 39(5): 931 - 938. [Abstract] [Full Text] [PDF]

				S. R. Salpeter, T. M. Ormiston, and E. E. Salpeter Meta-Analysis: Respiratory Tolerance to Regular {beta}2-Agonist Use in Patients with Asthma Ann Intern Med, May 18, 2004; 140(10): 802 - 813. [Abstract] [Full Text] [PDF]

				J.M. Wraight, R.J. Hancox, G.P. Herbison, J.O. Cowan, E.M. Flannery, and D.R. Taylor Bronchodilator tolerance: the impact of increasing bronchoconstriction Eur. Respir. J., May 1, 2003; 21(5): 810 - 815. [Abstract] [Full Text] [PDF]

				L. Prieto, V. Gutierrez, V. Torres, S. Uixera, and J. Marin Effect of Salmeterol on Seasonal Changes in Airway Responsiveness and Exhaled Nitric Oxide in Pollen-Sensitive Asthmatic Subjects* Chest, September 1, 2002; 122(3): 798 - 805. [Abstract] [Full Text] [PDF]