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Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma.
N Engl J Med. 1992 Oct 22; 327(17):1198-203.NEJM

Abstract

BACKGROUND

Asthma is characterized by hyperresponsiveness of the airways to bronchoconstrictive stimuli. Long-acting beta 2-adrenoceptor agonists have been introduced as a new therapeutic approach, but there is growing concern about whether control of asthma may deteriorate with the regular use of these agents. We investigated the long-term effects of the beta 2 agonist salmeterol on bronchodilation and on airway hyperresponsiveness to the bronchoconstrictive agent methacholine in mild asthma.

METHODS

In a parallel, double-blind study, 24 patients with mild asthma were randomly assigned to treatment with either inhaled salmeterol (50 micrograms, twice daily) (n = 12) or placebo (n = 12) during an eight-week trial. Methacholine challenge was performed before, during, and after the treatment period. Methacholine responsiveness was measured as the provocative concentration (PC20) that caused a 20 percent decrease in the forced expiratory volume in one second (FEV1).

RESULTS

There was a significant increase in FEV1 one hour after the inhalation of salmeterol (P = 0.006), which did not differ significantly on days 0, 28, and 56 of the treatment period (increase, 9.8, 9.4, and 8.8 percent of predicted FEV1, respectively; P = 0.91). On the first treatment day, salmeterol afforded significant protection against methacholine-induced bronchoconstriction, as shown by a 10-fold increase in the PC20 as compared with the value at entry (P less than 0.001). After four and eight weeks of treatment, however, the salmeterol-induced change in the PC20 was significantly attenuated (P less than 0.001) to only a twofold increase. Two and four days after treatment ended, the PC20 was not significantly different from the value before treatment (P = 0.15).

CONCLUSIONS

Regular treatment of patients with mild asthma with salmeterol leads to tolerance to its protective effects against a bronchoconstrictor stimulus, in this case inhaled methacholine, despite well-maintained bronchodilation. This finding raises concern about the effectiveness of prolonged therapy with long-acting beta 2-adrenoceptor agonists in asthma.

Authors+Show Affiliations

Department of Pulmonology, University Hospital Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1357550

Citation

Cheung, D, et al. "Long-term Effects of a Long-acting Beta 2-adrenoceptor Agonist, Salmeterol, On Airway Hyperresponsiveness in Patients With Mild Asthma." The New England Journal of Medicine, vol. 327, no. 17, 1992, pp. 1198-203.
Cheung D, Timmers MC, Zwinderman AH, et al. Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma. N Engl J Med. 1992;327(17):1198-203.
Cheung, D., Timmers, M. C., Zwinderman, A. H., Bel, E. H., Dijkman, J. H., & Sterk, P. J. (1992). Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma. The New England Journal of Medicine, 327(17), 1198-203.
Cheung D, et al. Long-term Effects of a Long-acting Beta 2-adrenoceptor Agonist, Salmeterol, On Airway Hyperresponsiveness in Patients With Mild Asthma. N Engl J Med. 1992 Oct 22;327(17):1198-203. PubMed PMID: 1357550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma. AU - Cheung,D, AU - Timmers,M C, AU - Zwinderman,A H, AU - Bel,E H, AU - Dijkman,J H, AU - Sterk,P J, PY - 1992/10/22/pubmed PY - 1992/10/22/medline PY - 1992/10/22/entrez SP - 1198 EP - 203 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 327 IS - 17 N2 - BACKGROUND: Asthma is characterized by hyperresponsiveness of the airways to bronchoconstrictive stimuli. Long-acting beta 2-adrenoceptor agonists have been introduced as a new therapeutic approach, but there is growing concern about whether control of asthma may deteriorate with the regular use of these agents. We investigated the long-term effects of the beta 2 agonist salmeterol on bronchodilation and on airway hyperresponsiveness to the bronchoconstrictive agent methacholine in mild asthma. METHODS: In a parallel, double-blind study, 24 patients with mild asthma were randomly assigned to treatment with either inhaled salmeterol (50 micrograms, twice daily) (n = 12) or placebo (n = 12) during an eight-week trial. Methacholine challenge was performed before, during, and after the treatment period. Methacholine responsiveness was measured as the provocative concentration (PC20) that caused a 20 percent decrease in the forced expiratory volume in one second (FEV1). RESULTS: There was a significant increase in FEV1 one hour after the inhalation of salmeterol (P = 0.006), which did not differ significantly on days 0, 28, and 56 of the treatment period (increase, 9.8, 9.4, and 8.8 percent of predicted FEV1, respectively; P = 0.91). On the first treatment day, salmeterol afforded significant protection against methacholine-induced bronchoconstriction, as shown by a 10-fold increase in the PC20 as compared with the value at entry (P less than 0.001). After four and eight weeks of treatment, however, the salmeterol-induced change in the PC20 was significantly attenuated (P less than 0.001) to only a twofold increase. Two and four days after treatment ended, the PC20 was not significantly different from the value before treatment (P = 0.15). CONCLUSIONS: Regular treatment of patients with mild asthma with salmeterol leads to tolerance to its protective effects against a bronchoconstrictor stimulus, in this case inhaled methacholine, despite well-maintained bronchodilation. This finding raises concern about the effectiveness of prolonged therapy with long-acting beta 2-adrenoceptor agonists in asthma. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/1357550/Long_term_effects_of_a_long_acting_beta_2_adrenoceptor_agonist_salmeterol_on_airway_hyperresponsiveness_in_patients_with_mild_asthma_ L2 - http://www.nejm.org/doi/full/10.1056/NEJM199210223271703?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -