Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial

Abstract

Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene 1 (CysLT 1 ) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils.Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19±64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second $65% of the predicted value and were being treated only with "as needed" inhaled b 2 -agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed.Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6±0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5±9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1± -1.4) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and b 2 -agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo.These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.

Up-Regulation of Cysteinyl Leukotriene 1 Receptor by IL-13 Enables Human Lung Fibroblasts to Respond to Leukotriene C4 and Produce Eotaxin

“…Intratracheal administration of LTD 4 promotes eosinophil sequestration into the airways (5,6). CysLTR antagonists reduce eosinophilic inflammation of the airways in asthma (7,8). The role of CysLTs in eosinophilic inflammation has been studied in several in vitro experiments.…”

Induced sputum cell counts: their usefulness in clinical practice

“…In a double blind, randomized, controlled, parallel group study over 4 weeks, montelukast improved clinical outcomes and reduced the sputum eosinophil count; during placebo treatment sputum eosinophils increased [72].…”

Mechanism of glutamine inhibition of cytosolic phospholipase a2 (cPLA2): Evidence of physical interaction between glutamine-Induced mitogen-activated protein kinase phosphatase-1 and cPLA2

“…Many investigators have reported an association between cPLA 2 metabolites and Th2 response in asthmatic reactions [33][34][35][36]. Importantly, LTs play a key role in dendritic cell influx into airways in asthma [37][38][39] which, in turn, results in inhibition of recruitment of T cells and eosinophils into asthmatic airways and late AHR. Regarding neutrophil infiltration, we reported previously that airway neutrophilia in the asthmatic lungs is mediated by LTB4 rather than CXC chemokines such as keratinocyte-derived chemokine and macrophage inflammatory protein (MIP)-2 [20], which are principally chemotactic for neutrophils.…”