Mucoactive therapy in COPD

Abstract

It has been shown that mucus hypersecretion is associated with greater susceptibility for chronic obstructive pulmonary disease (COPD), excess forced expiratory volume in 1 s decline, hospitalisations and excess mortality. The effects of mucoactive drugs on outcomes have been reviewed in several meta-analyses, the largest one including 26 studies. 21 studies were performed in patients with chronic bronchitis and five in patients with COPD. The majority of these trials were performed with N-acetylcysteine (n = 13) and carbocysteine (n = 3). Overall, there was a significant reduction in exacerbations (0.05 per patient per month) and the number of days with disability (0.56 days per patient per month). Mucolytics were well tolerated and the number of adverse events was lower than with placebo (odds ratio 0.78). In the largest and best designed study with N-acetylcysteine in 523 patients with COPD, the reduction in exacerbations was only observed in patients not taking inhaled corticosteroids. In addition, a 374 mL reduction in functional residual capacity was found. A recent large study (n = 709) with high-dose carbocysteine (1,500 mg·day⁻¹) demonstrated a significant effect on exacerbations (25% reduction) and also reported an improvement in health-related quality of life (-4.06 units in St George's Respiratory Questionnaire). It is unclear what the mechanisms underlying these effects may be and which phenotypes benefit from this treatment. On the basis of this evidence mucoactive drugs may deserve consideration in the long-term treatment of COPD.

Figures

FIGURE 1.

Flow chart showing of the number of studies incorporated in the Cochrane review. COPD: chronic obstructive pulmonary disease. #: <4% of the original number identified.

FIGURE 2.

Forest plot comparison of mucolytics versus placebo for the number of exacerbations per patient per month. Heterogenetity: Chi-squared 138.08; degrees of freedom 20 (p<0.00001); I2 96%. Test for overall effect: z-score 10.06 (p<0.000001). IV: linear instrumental variable regression. Reproduced from [23] with permission from the publisher.

FIGURE 3.

Forest plot comparison of mucolytics versus placebo for the number of patients with no exacerbations during the study period. Heterogenetity: Chi-squared 30.56; degrees of freedom 19 (p<0.05); I2 38%. Test for overall effect: z-score 11.28 (p<0.00001). Reproduced from [23] with permission from the publisher.

FIGURE 4.

Kaplan–Meier plot of the probability of a) being exacerbation free or b) having more than one exacerbation at each time-point during the study. ––––: carbocysteine; - - - -: placebo. Reproduced from [53] with permission from the publisher.