Dose Response of Inhaled Corticosteroids in Children With Persistent Asthma: A Systematic Review

OBJECTIVE: To assess the dose-response relationship (benefits and harms) of inhaled corticosteroids (ICSs) in children with persistent asthma.

METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared ≥2 doses of ICSs in children aged 3 to 18 years with persistent asthma. Medline was searched for articles published between 1950 and August 2009. Main outcomes of our analyses included morning and evening peak expiratory flow, forced expiratory volume in 1 second, asthma symptom score, β₂-agonist use, withdrawal because of lack of efficacy, and adverse events. Meta-analyses were performed to compare moderate (300–400 μg/day) with low (≤200 μg/day beclomethasone-equivalent) doses of ICSs.

RESULTS: Fourteen RCTs (5768 asthmatic children) that evaluated 5 ICSs were included. The pooled standardized mean difference from 6 trials revealed a small but statistically significant increase of moderate over low doses in improving forced expiratory volume in 1 second (standardized mean difference: 0.11 [95% confidence interval: 0.01–0.21]) among children with mild-to-moderate asthma. There was no significant difference between 2 doses in terms of other efficacy outcomes. Local adverse events were uncommon, and there was no evidence of dose-response relationship at low-to-moderate doses.

CONCLUSIONS: Compared with low doses, moderate doses of ICSs may not provide clinically relevant therapeutic advantage in children with mild-to-moderate persistent asthma. Additional RCTs are needed to clarify the dose-response relationship of ICSs in persistent childhood asthma.