Daily Use of Salmeterol Causes Tolerance to Bronchodilation with Terbutaline in Asthmatic Subjects

Jimmi Elers*, Ulla Strandbygaard, Lars Pedersen, Vibeke Backer
Respiratory and Allergy Research Unit, Bispebjerg Hospital, Copenhagen, Denmark

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© Elers et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Respiratory and Allergy Research Unit, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 København NV, Denmark; Tel: +45 35313569; Fax: +45 35312179; E-mail:



The purpose was to assess tolerance to terbutaline after daily use of long-acting β2- agonist (LABA) and further to evaluate two designs of reversibility test widely used in research and clinic in order to demonstrate tolerance.


Twenty-eight asthmatics were given daily LABA in 12 weeks and were randomized to challenge test and either conventional reversibility test with 2 puffs terbutaline or reversibility test with refracted doses (1 puff) every 5 min, total 4 puffs. FEV1 was measured pre-challenge, post-challenge, during and after reversibility test. All subjects had 3 visits: baseline, after 4 weeks and after 12 weeks of LABA treatment. All subjects were non-smokers, aged 18–45 years and had a positive methacholine challenge.


The analyses showed a significant fall in reversibility after 4 and 12 weeks of LABA treatment (p=0.001) in the group with the conventional reversibility test. The group with reversibility test using refracted doses also showed a significant fall in reversibility after 4 weeks of LABA treatment (p=0.017) followed by a similar trend after 12 weeks (p=0.054), however, we experienced an interfering number of dropouts at the last visit.


The bronchodilator response to terbutaline was significantly reduced in asthmatic subjects using daily LABA. The tolerance develops rapidly and is present after 4 weeks of treatment. Our study showed that both the conventional reversibility test and the reversibility test with refracted doses, combined with methacholine challenge is able to demonstrate tolerance to bronchodilator after daily use of LABA.

Keywords: Tolerance, tachyphylaxis, β-2-agonist, bronchodilator, asthma..