Forty-eight trials met the inclusion criteria. Nineteen trials (n=33,826) were included in the main analysis of the review. The trials ranged from 3 to 12 months in duration. The drop-out rate ranged from 2.9 to 24% for beta-agonists and from 2.9 to 25.7% for placebo. Seventeen trials were funded by pharmaceutical companies. Twenty-eight other trials did not provide information on exacerbations or asthma-related deaths and were only used for sensitivity analyses.
Out of a possible quality score of 9, nine studies scored 9 and ten scored 8.
The authors stated that there was no evidence of publication bias.
Hospitalisation for asthma exacerbations.
There was a statistically significant increase in the incidence of hospitalisation for asthma with beta-agonists compared with placebo (OR 2.6, 95% CI: 1.6, 4.3, P<0.001; 12 studies). There was no statistically significant heterogeneity between the studies. The pooled RD associated with beta-agonists was 0.7% (95% CI: 0.1, 1.3) over 6 months. The results for subgroup analyses were also reported.
Life-threatening asthma exacerbations.
There was a statistically significant increase in the incidence of life-threatening asthma exacerbations with beta-agonists compared with placebo when the results from 7 RCTs were pooled (OR 1.8, 95% CI: 1.1, 2.9, P=0.012). There was no statistically significant heterogeneity between the studies. The pooled RD associated with beta-agonists was 0.12% (95% CI: 0.01, 0.3) over 6 months. The results for subgroup analyses were also reported.
Asthma-related deaths.
Three trials reported deaths: two reported one death in the treatment group and none in the placebo group, while the third trial reported 13 deaths in the treatment group (n=13,174) and 3 in the placebo group (n=13,179). The pooled RD associated with beta-agonists was 0.07% (95% CI: 0.01, 0.1) over 6 months. The results for subgroup analyses were also reported.