SALMETEROL TACHYPHYLAXIS IN STEROID-TREATED ASTHMATIC SUBJECTS

Background - Tachyphylaxis to the protection afforded by salmeterol to bronchoconstrictor stimuli after regular use has been described in pa tients with mild asthma not receiving inhaled corticosteroids. The pre sent study was performed to investigate whether airway tachyphylaxis o ccurs in symptomatic asthmatic subjects receiving inhaled corticostero ids, the group for whom salmeterol is recommended in clinical practice . Methods - Thirty one adult patients with symptomatic chronic asthma who were receiving inhaled corticosteroids were randomised in a double blind manner and on a 2:1 basis to receive salmeterol 50 mu g (n = 22 ) or placebo (n = 9) twice daily. Baseline forced expiratory volume in one second (FEV,) was measured during the run-in period, on day 0, an d after four and eight weeks of regular treatment (following a 36 hour test drug washout period). Airway responsiveness to methacholine was measured one hour after administration of the test drug on these occas ions. Diary cards were kept throughout the study and for a two week fo llow up period. Results - Baseline FEV(1), was not significantly diffe rent between the treatment groups or between visits. There was signifi cant bronchodilatation one hour after salmeterol administration at 0, four, and eight weeks. No significant tachyphylaxis of the bronchodila tor action of salmeterol was seen. Protection against methacholine ind uced bronchoconstriction reduced from 3.3 doubling dilutions after the first dose of salmeterol to two doubling dilutions after four and eig ht weeks of regular treatment. Symptom scores and ''rescue'' salbutamo l use were significantly reduced during salmeterol treatment and dayti me improvements were maintained into the follow up period. Conclusions - Inhaled corticosteroids did not prevent tachyphylaxis to the protec tion afforded by salmeterol to methacholine induced bronchoconstrictio n. The clinical significance, if any, of these findings remains to be defined.