[Mucolytic and antioxidant agents for exacerbations of chronic obstructive pulmonary disease: A meta-analysis]

To assess the effects and safety of long-term oral mucolytic and antioxidant agents for exacerbations in patients with stable chronic obstructive pulmonary disease. And to further discuss the drug dose and concomitant ICS on the effects.

Systematic searches were performed in Medline and Google Scholar databases. Randomized controlled trials which compared regular oral mucolytic and antioxidant agents with placebo and reported exacerbations over a treatment period more than 3 months were selected. Stata version 11 was used for data analysis.

Ten RCTs involving 3 434 patients were identified. Compared with placebo, the use of mucolytic and antioxidant agents was associated with a reduction of 0.36 exacerbations per patient per year (95%CI 0.47 to 0.26). The subgroup analysis restricting to studies without concomitant ICS indicated that there was a larger decrease between the two groups (WMD=-0.58, 95% CI -0.89--0.27). The analysis of NAC dose on the effect indicated that high-dose NAC treatment could significantly reduce the exacerbations (WMD=-0.39, 95% CI -0.61--0.16, z=3.33, P=0.001). While in the low-dose NAC group, only those studies with low rate of concomitant ICS showed the effects (WMD=-1.25, 95% CI -1.99--0.51, z=3.32, P=0.001), the difference was not significant in studies with high rate of concomitant ICS (WMD=-0.06, 95% CI -0.29--0.17, z=0.5, P=0.617). There was no difference in FEV1 improvement (SMD=0.03, 95%CI -0.09～0.15, z=0.49, P=0.626), but FEF 25%-75% showed a significant improvement (SMD=0.41, 95% CI 0.13-0.68, z=2.90, P=0.004).

The use of mucolytic and antioxidant agents is associated with a reduction in the number of exacerbations. The effects may be larger in those patients without concomitant ICS. High-dose NAC treatment may be more effective than low-dose group, while the latter may be effective only when the rate of concomitant ICS was low.