Objective: 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.
Methods: 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.
Results: 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).
Conclusion: 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.