ABSTRACT
OBJECTIVE：To systematically e valuate the efficacy and safety of expectorant/antioxidants in the treatment of chronic obstructive pulmonary disease （COPD），and to provide evidence-based reference for clinical use. METHODS ：Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，CBM，CNKI，VIP，Wanfang database ，etc.，randomized controlled trials（RCTs）about expectorant/antioxidants （trial group ）versus placebo （control group ）in the treatment of COPD were collected during the inception to May 2021. After literature screening and data extraction ，the quality of included literatures were evaluated with risk bias evaluation tool recommended by Cochrane systematic evaluator manual 5.1.0. The consistency check was performed by using Gemtc 14.3 software；network Meta-analysis ，clustering and hierarchical sorting were performed with Stata 15.1 software. The publication bias was analyzed by inverted funnel plot. RESULTS ：A total of 12 RCTs，involving 4 637 patients，were included. Five interventions measures were involved ，such as low-dose N-acetylcysteine （NAC），high-dose NAC ，carbo- cisteine， erdosteine and placebo. The results of network Meta-analysis showed that in terms of annual acute aggrava- tion rate ，the patients receiving high-do se NAC [MD ＝－0.45， 163.com 95％CI（－0.74，－0.17），P＜0.05]，carbocisteine [MD ＝－0.59，95％CI（－0.86，－0.32），P＜0.05] and erdosteine [MD ＝－0.26，95％CI（－0.51，－0.01），P＜0.05] in trial group were significantly lower than those in control group ；the annual acute aggravation rate of patients receiving high-dose NAC[MD ＝－0.55， 95％CI（－0.98，－0.11），P＜0.05] and carbocisteine [MD ＝－0.69，95％CI（－1.11，－0.26），P＜0.05] in trial group were significantly lower than those receiving low-dose of NAC ，there was no statistical significance among other groups （P＞0.05）； probability cumulative ranking results （calculated by the area under the curve ）of its network Meta-analysis was carbocisteine ＞ high-dose NAC ＞erdosteine＞placebo＞low-dose NAC. In terms of the incidence of ADR ，there was no statistical significance among groups （P＞0.05）；probability cumulative ranking results （calculated by the area under the curve ） of its network Meta-analysis was erdosteine ＞high-dose NAC ＞low-dose NAC ＞placebo＞carbocisteine. The results of clustering and hierarchical ranking showed that the efficacy and safety of the five interventions could be grouped into three categories ，including placebo and low-dose NAC with low efficacy and safety ，carbocisteine with good efficacy but low safety ，and high-dose NAC and erdosteine with good efficacy and safety. The results of publication bias showed that taking the annual acute exacerbation rate as the index ， there was a greater possibility of publication bias in this study ；taking the incidence of adverse event as index ，there was little possibility of publication bias in this study. CONCLUSIONS ：NAC，carbocisteine and erdosteine all can reduce the annual acute aggravation rate and have low incidence of ADR. Carbocisteine is the best in terms of annual acute aggravation rate ，erdosteine is the best in terms of safety. High-dose NAC and erdosteine are both better in term of efficacy and safety.