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


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


METHODS
Respiratory medicine department of a university hospital.


METHODS
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.


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.
Gompertz
Simon
S
Department of Respiratory Medicine, Queen Elizabeth Hospital, Birmingham, UK. sgomp@doctors.org.uk
Stockley
Robert A
RA
D000368:Aged; D029481:Bronchitis, Chronic / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008297:Male; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011804:Quinolines / Q000627:therapeutic use*
D016859:Lipoxygenase Inhibitors; D011804:Quinolines; C079315:2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid; D007975:Leukotriene B4