Thirty-two RCTs (n=4,045) were included: 16 trials (n=1,998) of children and adolescents and 16 trials (n=2,047) of adults.
Twenty-six studies were double-blinded. The Jadad scores ranged from 1 to 5 out of a possible 5.
The combination of inhaled anticholinergic and beta-2 agonist treatment was associated with statistically significant reductions in the risk of hospital admission for children and adolescents (RR 0.73, 95% CI: 0.63, 0.85; based on 10 studies; NNT 13, 95% CI: 9, 28) and for adults (RR 0.68, 95% CI: 0.53, 0.86; based on 9 studies; NNT 14, 95% CI: 9, 30), compared with beta-2 agonists alone. There was no evidence of publication bias or heterogeneity (I-squared 0% for the analysis of children and 13.8% for adults). Subgroup analyses suggested that the greatest effect was seen in children and adults with the most severe asthma attacks treated with multiple doses of anticholinergics.
Combined treatment was also associated with statistically significant increases in spirometric parameters 1 to 2 hours after the last treatment (either the percentage change in forced expiratory volume, peak expiratory flow rate, or respiratory resistance) for children and adolescents (SMD -0.54, 95% CI: -0.81, -0.28; based on 9 studies) and for adults (SMD -0.36, 95% CI: -0.49, -0.23; based on 16 studies). There was significant heterogeneity for both groups (I-squared 57.3% for children and 41.3% for adults). There was no evidence of publication bias. It appeared that combined treatment was most effective in those receiving more than two doses of anticholinergics.
Three studies of children found a significant reduction in clinical score after combined treatment (SMD -0.29, 95% CI: -0.51, -0.07). There was no evidence of a difference in side-effects, such as tremor, amongst patients treated with single or multiple doses. There was also no evidence that the combined treatment affected heart rate amongst adults.