The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days. One hour before each challenge they were pretreated in double-blind fashion using a metered-dose inhaler and Babyhaler spacer. Placebo was given before one challenge, and either 25, 50 or 100 microg of salmeterol before the other. Both the dose and treatment order were random. The provocative concentration of methacholine causing wheeze (PCwheeze) was measured on each occasion. Studies were terminated when wheeze occurred or arterial oxygen saturation (Sa,o2) fell below 91%. Of the 42 children enrolled, 33 completed the study. Two subjects refused the challenge test, two failed to return and five developed upper respiratory tract infections or wheeze between the two tests. The mean (range) age of the population was 27 (8-46) months. Ratios of PCwheeze between treatment and placebo challenges were calculated for each dosage group. The treatment/placebo ratios (95% confidence intervals) were 1.2 (0.6-2.4) for 25 microg, 2.5 (1.4-4.6) for 50 microg (p<0.01), and 4.0 (2.1-7.4) (p<0.001) for 100 microg doses. In recurrently wheezy children aged <4 yrs a single dose of salmeterol between 25 and 100 microg has a dose-dependent effect on methacholine-induced wheeze, and this is significantly different from placebo at 50 and 100 microg. This study suggests that the Babyhaler effectively delivers salmeterol to children <4 yrs of age and that doses between 50-100 microg are efficacious.