Prevention of COPD exacerbation by lysozyme: a double-blind, randomized, placebo-controlled study

Abstract

Background/aim

Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation.

Methods

In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg) or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication. The primary endpoint was exacerbation rate.

Results

A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression). However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6). Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group. The levels of improvement in forced expiratory volume in 1 second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52 weeks of the study.

Conclusion

The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation.

Keywords:

• lysozyme
• COPD exacerbation
• forced expiratory volume in 1 second
• COPD assessment test

Acknowledgments

We would like to express our appreciation to the principal investigators and their staff at the 47 Japanese medical institutions who participated in the current study. This study was conducted with funds from Aska Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., and Eisai Co., Ltd.

Disclosure

YF, MI, KT, and HI are consultants for Eisai Co., Ltd. Moreover, KS, HM, YM, and YS are employees of Eisai Co., Ltd. The authors report no other conflicts of interest in this work.