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Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.

ABSTRACT: Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations.We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization.Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation. Primary outcome measure was hospital length of stay; secondary outcomes included treatment failure and biomarkers of leukotriene production.Sixty subjects were randomized to zileuton and 59 to placebo (the study was stopped short of enrollment goals because of slow recruitment). There was no difference in hospital length of stay (3.75 +/- 2.19 vs. 3.86 +/- 3.06 days for zileuton vs. placebo, p = 0.39) or treatment failure (23% vs. 27% for zileuton vs. placebo, p = 0.63) despite a decline in urinary LTE(4) levels in the zileuton-treated group as compared to placebo at 24 hours (change in natural log-transformed ng/mg creatinine -1.38 +/- 1.19 vs. 0.14 +/- 1.51, p < 0.0001) and 72 hours (-1.32 +/- 2.08 vs. 0.26 +/- 1.93, p<0.006). Adverse events were similar in both groups.While oral zileuton during COPD exacerbations that require hospital admission is safe and reduces urinary LTE(4) levels, we found no evidence suggesting that this intervention shortened hospital stay, with the limitation that our sample size may have been insufficient to detect a modest but potentially meaningful clinical improvement.

SUBMITTER: Woodruff PG

PROVIDER: S-EPMC3775706 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.

Woodruff Prescott G PG Albert Richard K RK Bailey William C WC Casaburi Richard R Connett John E JE Cooper John A D JA Criner Gerard J GJ Curtis Jeffrey L JL Dransfield Mark T MT Han Meilan K MK Harnden Sarah M SM Kim Victor V Marchetti Nathaniel N Martinez Fernando J FJ McEvoy Charlene E CE Niewoehner Dennis E DE Reilly John J JJ Rice Kathryn K Scanlon Paul D PD Scharf Steven M SM Sciurba Frank C FC Washko George R GR Lazarus Stephen C SC

COPD 20110201 1

<h4>Rationale</h4>Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations.<h4>Objective</h4>We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization.<h4>Methods</h4>Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times d ...[more]

PMID: 21299475

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Project description:PurposeInfections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes.Patients and methodsOne-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student's t-test and Mann-Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential confounders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models.ResultsIn the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25-0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10-0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723).ConclusionAdvanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.

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Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.

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Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.

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