Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol

Continuous treatment with a short-acting Pz-agonist can lead to reduced bro nchodilator responsiveness during acute bronchoconstriction. This study eva luated bronchodilator tolerance to salbutamol following regular treatment w ith a long-acting Pz-agonist, formoterol. The modifying effect of intraveno us corticosteroid was also studied. Ten asthmatic subjects (using inhaled steroids) participated in a randomise d, double-blind, placebo-controlled, cross-over study. Formoterol 12 mug b. i.d. or matching placebo was given for 10-14 days with >2 weeks washout. Fo llowing each treatment, patients underwent a methacholine challenge to indu ce a fall in forced expired volume in one second (FEV1) of at least 20%, th en salbutamol 100 mug, 100 mug, and 200 mug was inhaled via a spacer at 5 m in intervals, with a further 400 mug at 45 min. After a third single-blind formoterol treatment period, hydrocortisone 200 mg was given intravenously prior to salbutamol. Dose-response curves for change in FEV1 with salbutamo l were compared using analysis of covariance to take account of methacholin e-induced changes in spirometry. Regular formoterol resulted in a significantly lower FEV1 after salbutamol at each time point compared to placebo (p < 0.01). The area under the curve s (AUCs) for 15 (AUC(0)-15) and 45 (AUC(0)-45) min were 28.8% and 29.5% low er following formoterol treatment (p < 0.001). Pretreatment,vith hydrocorti sone had no significant modifying effect within 2 h of administration. It is concluded that significant tolerance to the bronchodilator effects of inhaled salbutamol occurs 36 h after stopping the regular administration o f formoterol. This bronchodilator tolerance is evident in circumstances of acute bronchconstriction.