A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD

Chest. 2002 Jul;122(1):289-94. doi: 10.1378/chest.122.1.289.


Study objective: Patients with COPD classically have neutrophilic bronchial inflammation and raised airway concentrations of the neutrophil chemoattractant leukotriene B(4) (LTB(4)). A small phase II trial was conducted to assess the effects of a leukotriene synthesis inhibitor on bronchial inflammation in patients with stable COPD.

Design: A randomized, double-blind, placebo-controlled, parallel-group study.

Setting: Respiratory medicine department of a university hospital.

Patients and intervention: Seventeen patients with chronic bronchitis and COPD (mean FEV(1), 35.5% predicted; SD, 14.8% predicted) were randomized to receive 14 days of the oral leukotriene synthesis inhibitor BAYx1005 (500 mg bid) or placebo.

Measurements and results: Spontaneous sputum samples obtained at baseline and at the end of treatment were assayed for LTB(4), myeloperoxidase (an indirect marker of neutrophil numbers and/or activation), and chemotactic activity (Boyden chamber). After 14 days, there were no significant differences (p > 0.05) in absolute LTB(4) concentrations between the two treatment groups. However, BAYx1005 treatment produced a significantly greater median reduction in LTB(4) of - 3.1 nM (interquartile range [IQR], - 9.6 to - 0.2 nM) vs 3.0 nM (IQR, - 0.3 to 8.5 nM) [p = 0.001], with concentrations decreasing from 8.0 nM (IQR, 4.3 to 24.4 nM) at baseline to 4.2 nM (IQR, 1.9 to 11.9 nM) at the end of treatment (p = 0.03). There were no changes in the placebo group and no differences in sputum myeloperoxidase concentration or chemotaxis between the two treatment arms (p > 0.05).

Conclusions: This small study suggests that a leukotriene synthesis inhibitor can produce modest reductions in some measures of neutrophilic bronchial inflammation in patients with COPD. This class of anti-inflammatory agent requires further study in larger numbers of patients to determine clinical benefit.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bronchitis, Chronic / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Leukotriene B4 / metabolism
  • Lipoxygenase Inhibitors / therapeutic use*
  • Male
  • Pulmonary Diffusing Capacity / drug effects*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Quinolines / therapeutic use*


  • Lipoxygenase Inhibitors
  • Quinolines
  • 2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid
  • Leukotriene B4