Childhood evaluation of salmeterol tolerance--a double-blind randomized controlled trial

Long acting beta(2)-agonists (LABA) are widely used in children with asthma. Data from adults suggest that there is tachyphylaxis particularly to the bronchoprotective effects of LABA. There are no data in children. To determine whether LABA are subject to tachyphylaxis in school-aged children. Children were eligible for participation if they remained symptomatic on 400 microg of beclometasone dipropionate equivalent/day. Participants undertook a 4-wk run in period with open-label fluticasone 100 microg BD via Diskus. Children were then randomized to receive fluticasone 100 microg BD or salmeterol/fluticasone 50/100 microg BD via Diskus in a double-blind manner. Children underwent spirometry, cold air challenge and salbutamol reversibility testing at baseline, 4 and 8 wk. 37/42 children completed the study. There were significant improvements in basal FEV1 (% predicted) in the salmeterol/fluticasone group (n = 21) (+6.4% (95% CI: 2.4-10.5) p = 0.0033) but not in the fluticasone group (n = 16) [+1.2 (95% CI: -3.4 to 5.8) p = 0.5900]. There was a non-significant reduction in fall in FEV1 provoked by cold air in both groups. There was a significant lessening in the acute salbutamol response after 8 wk in the salmeterol/fluticasone group [-11.4% (95% CI: -17.6 to -5.2) p = 0.0010] but not in the fluticasone group [-1.6% (95% CI: -9.8 to 6.6) p = 0.6827]. Salmeterol/fluticasone therapy significantly improves basal FEV(1) in asthmatic children however, there is negligible additional bronchoprotection by week 4 of treatment and there is significant attenuation of salbutamol responsiveness when compared with fluticasone alone. Some of this reduction in salbutamol response may relate to the concurrent improvements in baseline lung function.