title: Prevention of COPD exacerbation by lysozyme: a double-blind, randomized, placebo-controlled study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Fukuchi
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Kai
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyagishi
authors.affiliation: Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Marukawa
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000368:Aged; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009113:Muramidase / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000517:prevention & control*
chemical_list: D009113:Muramidase
keywords: COPD assessment test; COPD exacerbation; forced expiratory volume in 1 second; lysozyme