The impact of antileukotriene therapy on markers of airway inflammation

Asthma is a chronic, persistent inflammatory condition modulated by a variety of inflammatory cells and mediators. The current 'gold standard' asthma maintenance medication is an inhaled corticosteroid, which controls asthma via its anti-inflammatory effects in the airway. In order to be successful, new controller medications must have the ability to block infiltration and activation of inflammatory cells in the airway. Antileukotriene agents, such as the cysteinyl leukotriene receptor antagonist zafirlukast ('Accolate'), show these effects following allergen challenge in the lung. Forty-eight hours after segmental allergen challenge (SAC), bronchoalveolar lavage (BAL) fluid recovered from patients administered zafirlukast (20 mg b.i.d.), showed significantly lower concentrations of basophils and histamine than that from patients who received placebo (p < 0.01), and significantly lower superoxide production from purified alveolar macrophages (p < 0.01). In a subsequent study, zafirlukast (160 mg b.i.d.) significantly reduced the number of basophils and eosinophils in BAL fluid 48 h after SAC. Spontaneous superoxide release from alveolar macrophages was also significantly reduced by zafirlukast. Studies with other antileukotriene agents, such as the 5-lipoxygenase inhibitor zileuton, have demonstrated decreased eosinophilia in BAL fluid following allergen challenge and in patients with nocturnal asthma. Collectively, these data suggest that cysteinyl leukotrienes amplify inflammation, and that antileukotriene agents can reduce airway inflammation in asthma.