Twelve RCTs (507 patients) were included.
The methodological scores ranged from 0.35 to 0.81 with a mean of 0.61. Agreement among investigators for methodological score was 0.88. The number of positive studies favouring delivery by metered-dose inhaler, that would be required to reject an alternative hypothesis of equivalence with a small effect size of 0.2, was 13 studies.
Overall FEV1 effect size between metered-dose inhaler and wet nebulizer delivery was -0.02 (95%CI: -0.20, 0.16; P > 0.10). Test for heterogeneity P < 0.001. Sensitivity analysis was performed by omitting one study with a high effect size giving an overall effect size, of the remaining studies = 0.09 (95%CI: -0.09, 0.27). Heterogeneity after this omission was no longer present. Further sensitivity analysis was performed by including 5 of 6 excluded studies, giving overall effect size = 0.05 (95%CI: -0.11, 0.20).
A priori hypotheses tested were as follows:
Subgroup analysis of patients with asthma compared to those with chronic obstructive airways disease: effect size for asthma patients (8 studies, N = 292 patients) was -0.17 (95%CI: -0.41, 0.07), compared to effect size for chronic obstructive airways disease patients (3 studies, N = 48 patients) of 0.23 (95%CI: -0.35, 0.81). Comparison of sub-groups P > 0.10.
Different doses of beta-agonist: Equivalent doses (3 studies, N= 135 patients) effect size = 0.04 (95%CI: -0.30, 0.37); Standard dose of bronchodilators (6 studies, N = 217 patients) effect size = 0.05 (95%CI: -0.22, 0.33); Equal doses of metaproterenol (1 study, N = 100 patients) effect size = 0.06 (95%CI: -0.34, 0.45).
Double blind studies (6 studies, N = 269 patients) effect size = -0.02 (95%CI: -0.26, 0.23); open studies (6 studies, N = 238 patients) effect size = -0.02 (95%CI: -0.28, 0.24).
Relation of effect size to methodological quality: weak negative correlation (c) = - 0.21).