Bronchodilator response to salbutamol after chronic dosing with salmeterol or placebo

Abstract

It has been hypothesized that regular inhaled beta2-agonist therapy causes desensitization of beta2-receptors. The aim of this study was to define whether beta2-receptor desensitization occurs after treatment with the long-acting beta2-agonist salmeterol, assessed by measuring the bronchodilator response to cumulative repeated doses of inhaled salbutamol before and after treatment. Forty nine stable adult patients with asthma were randomized to receive either salmeterol 50 microg b.d. or placebo b.d. from an Accuhaler for 4 weeks after an initial 2 week run-in period without beta2-agonists. All patients were receiving inhaled corticosteroids. Bronchodilator responsiveness to cumulative repeated doses of inhaled salbutamol were measured before and 12 and 36 h after the last dose of study treatment. The primary efficacy endpoint was the peak forced expiratory volume in one second (FEV1) response before and after treatment. There were no significant differences between the two treatment groups in the absolute peak FEV1 or maximal peak expiratory flow (PEF) results 12 or 36 h after the last dose of study treatment. Significantly higher clinic lung function and diary card parameters were noted in the salmeterol group when compared to the placebo-treated patients, demonstrating the beneficial effects of regular salmeterol. Regular salmeterol usage did not lead to reduced efficacy of usual or higher than usual doses of salbutamol.

Decreased bronchodilating effect of salbutamol in relieving methacholine induced moderate to severe bronchoconstriction during high dose treatment with long acting beta2 agonists

“…Others have determined the absolute values of lung function16-18 and found no reduction in the sensitivity to the bronchodilating effects of salbutamol. Probable explanations are differences in baselines16-18 and in the time of the last dose of long acting β 2 agonist (within 12 hours17 18 or after 12 hours11-13 15 16). Also, unlike this study, concomitant β 2 agonist rescue medication was used during placebo treatment in some studies17 18 and some remaining β 2 receptor stimulation may have induced the reduced sensitivity.…”

Determinants of the bronchodilation response to salbutamol on histamine-induced bronchoconstriction

“…It is difficult to assess in stable asthmatic patients in whom there is usually no resting bronchoconstriction. 1,2 Therefore, it has become popular to assess the bronchodilator effect of SABAs on induced bronchoconstriction, especially in studies investigating the development of bronchodilator tolerance to SABAs during regular treatment with b 2 -adrenoreceptor agonists. [3][4][5][6][7][8][9][10] The bronchoconstriction has usually been induced pharmacologically [3][4][5][6][7][8]11 or, less often, by exercise.…”

Is there a problem with inhaled long-acting β-adrenergic agonists?

“…When the response has been expressed in this manner, no reduction in the response to single or multiple doses of albuterol has been observed after regular use of salmeterol. 57,58 The response to albuterol was preserved both in subjects using and those not using inhaled corticosteroids (Fig 1). 57 The effect of regular use of salmeterol on the response to albuterol has also been examined in patients presenting to an emergency department with acute asthma.…”