Effect of n-acetylcysteine against mucus hypersecretion in COPD

<bold>Background:</bold> N-acetylcysteine (NAC) is a mucolytic drug, with also antioxidant and anti-inflammatory activities, effective in the treatment of COPD. Although mucus plugs increase the risk of death in COPD patients (1), no studies have investigated the real effect of NAC against mucus hypersecretion (MHS). <bold>Aim:</bold> To assess the efficacy of NAC against MHS by assessing the expression of MUC5AC. <bold>Methods:</bold> A meta-analysis was performed on original studies reporting the effect of NAC against the gene and/or protein expression of MUC5AC in pre-clinical models of MHS. Since data were reported according to different metrics, standardized mean difference (SMD) was used to describe the effect estimates. The study was performed according to the PRISMA-P guidelines and the protocol was submitted to PROSPERO (506363). <bold>Results:</bold> The pre-clinical models of MHS included the exposure of airway cells to virus, bacteria, neutrophil elastase, oxidant compounds, cigarette smoke, and cytokines. NAC significantly (P<0.001) reduced the intracellular (−2.64 SMD 95%CI -3.14 – -2.15; I^2=69.15, P=0.001) and extracellular (−2.70 SMD 95%CI -3.29 – -2.11; I^2=48.90, P=0.001) protein expression of MUC5AC vs. positive control. NAC also significantly (P<0.001) reduced the gene expression of MUC5AC (−1.25 SMD 95%CI -1.54 – -0.96; I^2=28.56, P=0.056) vs. positive control. Sensitivity analysis resolved the detected heterogeneity (I^2>50%) and did not significantly (P>0.05) change the effect estimates. <bold>Conclusions:</bold> NAC is effective in reducing the gene and protein expression of MUC5AC, suggesting that long term treatment with NAC may elicit beneficial impact against mortality in COPD. 1. Diaz et al., JAMA. 2023;329:1832-1839.