Impact of Mucolytic Agents on COPD Exacerbations: A Pair-wise and Network Meta-analysis

Abstract

Mucolytics are potentially useful for the management of chronic obstructive pulmonary disease (COPD), although there is conflicting advice on their use in different guideline documents. Furthermore, there is paucity of data comparing the efficacy of the different mucolytic agents in reducing the odds of COPD exacerbations. We performed pair-wise and network meta-analyses to evaluate the impact of mucoly-tics in COPD. Randomized clinical trials lasting at least 3 months and investigating the effects of mucolytics on COPD exacerbations were identified from published studies and repository databases. Mucolytics significantly reduced the odds of exacerbation vs. placebo (11 studies analyzed: odds ratio (OR) 0.51, 95% confidence interval (CI) 0.39-0.67; p < 0.001). The most effective drugs were carbocysteine, erdosteine, and N-acetylcysteine 1,200 mg/day (SUCRA 68.0-79.0%), whereas the OR was similar to placebo for ambroxol and N-acetylcysteine 600 mg/day. Only N-acetylcysteine 1,200 mg/day significantly protected against exacerbations vs. placebo (2 studies analyzed: OR 0.56, 95% CI 0.35-0.92; p < 0.05; high quality of evidence). A signal of effectiveness was detected for carbocysteine (2 studies analyzed: OR 0.45, 95% CI 0.20-1.01; p ≥ 0.05; moderate quality of evidence). Specific differences in study designs and patient-related characteristics, such as history of exacerbations and ethnicity, were potential effect modifiers for our statistical models, whereas neither respiratory function nor the use of corticosteroids influenced the analysis. This meta-analysis demonstrates that mucolytics are useful in preventing COPD exacerbations as maintenance add-on therapy to patients with frequent exacerbations. The effectiveness of mucolytics is independent of the severity of airway obstruction and the use of inhaled corticosteroids.

European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD

“…Mucolytics are potentially useful for the management of COPD in patients that have tenacious secretions. A Cochrane review [111] and meta-analysis [112] found that mucolytic therapy led to an increase possibility of being exacerbation-free compared to placebo. However, due to much heterogeneity between the studies, these data should be interpreted with caution.…”

Oxidative stress in asthma: Part of the puzzle

“…116,118 According to a meta-analyses, NAC was able to decrease the exacerbation rate in patients with chronic obstructive pulmonary disease (COPD) when used as an add-on therapy at 1200 mg daily. 119 In contrast, in a randomized controlled study, NAC was found to be ineffective to prevent the decrease in lung function and exacerbations in patients with COPD. 120 Another study showed that NAC produced no significant benefit when added to conventional treatment during an asthma attack.…”

Efficacy and safety profile of xanthines in COPD: a network meta-analysis

“…The risk of bias for the impact of xanthines on lung function and their safety profile in stable COPD patients was assessed via the consistency/inconsistency analysis to check whether the outcomes resulting from the consistency and inconsistency models fit adequately with the line of equality, as previously described [19]. Furthermore, the inconsistency of evidence was also assessed by quantifying the inconsistency factor, indicating whether one of the treatment had a different effect when it was compared with the others [20].…”

“…Meta-regression analysis was performed to examine the source of heterogeneity between studies and identify potential confounder covariates specifically for the impact of xanthines on lung function and the risk of adverse events [19].…”