Role of leukotriene receptor antagonists in asthma.

Asthma is a chronic inflammatory disease that affects >300 million people worldwide. However, inhaled corticosteroids (ICS), the gold standard therapy for persistent asthma, cannot suppress every component of airway inflammation and often fail to adequately penetrate the small airways in order completely suppress eosinophilia. Cysteinyl leukotrienes are important inflammatory factors that are involved in asthma and allergic diseases, and montelukast, a cysteinyl leukotriene receptor antagonist (LTRA), is a competitive antagonist of these substances for the cysteinyl leukotriene type-1 receptor 1 (LTR1). Montelukast monotherapy has been shown to relieve the clinical symptoms of mild persistent asthma. As either a monotherapy or in combination with ICS, montelukast provides clinically relevant improvements to various asthma-related parameters, including symptoms, lung function, quality of life, and asthma exacerbations, and has been found to reduce eosinophilic airway inflammation by downregulating Mac-1 expression and eosinophil chemotaxis in patients with chronic asthma. Furthermore, montelukast has been reported to produce bronchoprotective effects against both specific and nonspecific bronchoactive stimuli. When treating childhood asthma, montelukast demonstrates faster clinical responses than ketotifen, including improved exhaled nitric oxide, peak expiratory flow, and asthma scores within 1 week. Similarly, in patients with allergic rhinitis, montelukast produces substantial improvements in symptoms and quality of life. The anti-inflammatory effects of LTRA have been reported widely in both in vivo and in vitro studies. Several studies have reported that LTRA may have anti-inflammatory effects, not only as an antagonist to LTR1, but also as an inhibitor of inflammatory cells. For example, montelukast and zafirlukast, two LTRAs, significantly downregulate monocyte chemoattractant protein-1 (MCP-1)-induced chemotaxis of human primary monocytes via the downregulation of MCP-1-induced [Ca]i and p38 MAPK expression. Airway inflammation, hyperresponsiveness, and remodeling are the fundamental components of the subsequent pathogenesis that leads to the symptoms and changes in