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

• Published in: Pediatric allergy and immunology 2010-03, Vol.21 (2p1), p.336-344
• Main Authors: Carroll, W. D., Jones, P. W., Boit, P., Clayton, S., Cliff, I., Lenney, W.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - adverse effects; Adrenergic beta-Agonists - therapeutic use; Albuterol - adverse effects; Albuterol - analogs & derivatives; Albuterol - therapeutic use; Androstadienes - therapeutic use; Anti-Asthmatic Agents - adverse effects; Anti-Asthmatic Agents - therapeutic use; asthma; Asthma - drug therapy; Beclomethasone - therapeutic use; beta-2 agonists; Biological and medical sciences; Child; Chronic obstructive pulmonary disease, asthma; Female; Fluticasone; Forced Expiratory Volume - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Humans; Male; Medical sciences; Pneumology; salmeterol; Salmeterol Xinafoate; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Tachyphylaxis; Treatment Outcome
• ISSN: 0905-6157; 1399-3038
• DOI: 10.1111/j.1399-3038.2009.00927.x

Carroll WD, Jones PW, Boit P, Clayton S, Cliff I, Lenney W. Childhood evaluation of salmeterol tolerance – a double‐blind randomized controlled trial. 
Pediatr Allergy Immunol 2010: 21: 336–344.
© 2009 John Wiley & Sons A/S Long acting β2‐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 μg of beclometasone dipropionate equivalent/day. Participants undertook a 4‐wk run in period with open‐label fluticasone 100 μg BD via Diskus™. Children were then randomized to receive fluticasone 100 μg BD or salmeterol/fluticasone 50/100 μg 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 FEV1 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.