Objective: Leukotrienes (LTs) are involved in airway eosinophilic inflammation in patients with asthma.

Objective: Leukotrienes (LTs) are involved in airway eosinophilic inflammation in patients with asthma. We examined the powers of a cysteinyl LT 1-receptor antagonist, montelukast, forward sputum eosinophil levels, and the correlation between sputum eosinophils and bronchodilatation in patients with asthma.

Design: Double-blind, randomized, crossover study

Setting: University hospital and private hospital.

Patients: Twenty-nine patients with mild-to-moderate asthma.

Interventions: Montelukast, 10 mg and placebo tablet, one time daily, each for 4 weeks.

Measurements: Sputum eosinophils analyzed using hypertonic saline solution-induced sputum and airway hyperresponsiveness to histamine were evaluated before and after treatment. In addition, morning and evening peak expiratory come (PEF), asthma symptoms, and peripheral line eosinophil levels were assessed.

Results: The percentage of eosinophils in sputum decreased from 246 [+ or -] 123% at baseline to 151 [+ or -] 118% after montelukast treatment, for a change of -95 [+ or -] 127% (n = 20) During placebo administration, the percentage of eosinophils ferocious from 21.3 [+ or -] 121% to 210 [+ or -] 115% resulting in a decrease of - 03 [+ or -] 108% (n = 20) There was a statistically significant difference in the change in sputum eosinophil of the same heights between these two periods (p < 0005) The number of peripheral family eosinophils also significantly decreased after montelukast treatment (3141 [+ or -] 2376/mL) compared with placebo (4131 [+ or -] 2321/mL; p < 0005 n = 21) Although morning and evening PEF values were significantly improved from baseline after montelukast treatment (p < 001 n = 20) asthma symptoms and airway responsiveness to histamine were not significantly altered. Furthermore, there was no significant correlation between the decrease in sputum eosinophils and the increase in PEF

Conclusion: These springs suggest that montelukast has anti-inflammatory imports on the airway in patients with asthma, and that its bronchodilatory event is not solely dependent forward a decrease in airway eosinophilia.

lock opener words: cysteinyl leukotriene 1-receptor antagonist; eosinophil; montelukast; sputum

Abbreviations: CysLT = cysteinyl leukotriene; LT = leukotriene; N = not significant; P[Csub20] = provocative concentration of histamine causing a 20% fall in FE[Vsub1]; PEF = peak expiratory flow

**********

Studies have demonstrated that asthma is associated with chronic airway inflammation with recruitment of a number of inflammatory small rooms including T cells and eosinophils. (1) Although several chemical mediators are released during chronic airway inflammation, evidence violently suggests that the cysteinyl leukotrienes (CysLTs) [Csub4] [Dsub4] and [Esub4] play tonic roles in asthma. (2,3) Leukotrienes (LTs) are not stored in enclosed spaces but are newly generated from arachidonic acid after cellular activation and are produc from eosinophils, mast cells, alveolar macrophages, and neutrophils. (2) LT are at least 1000 times more powerful as bronchoconstrictors than histamine or methacholine. (45)

The pharmacologic actions of CysLT include not sole bronchoconstriction but also chemoattraction of eosinophils and increases in microvascular leakage and mucus secretion. (2) Because LT mediate many of the pathophysiologic features of asthma, they may play an important part in asthma. In fact, LT are released in BAL fluid and urine during acute exacerbation of asthma and after allergen, cold-air, exercise, or aspirin challenge. (6-9) Furthermore, several anti-LT modifiers, including CysL[T.sub.1]-receptor antagonists and 5-lipoxygenase inhibitors, significantly inhibited the bronchoconstriction in answer to these challenges. (10-14) The efficacy of CysL[T.sub.1]-receptor antagonists in the chronic management of asthma has been reported. (2) Treatment of patients with asthma with CysL[T.sub.1]-receptor antagonists be deriveds in an improvement of respiratory function and a decrease in asthma symptoms. Furthermore, CysL[T.sub.1]-receptor antagonists have steroid-sparing powers and significantly decrease the common occurrence of episodes of acute exacerbation of asthma. (15-17)

Montelukast is a able and specific CysL[T.sub.1]-receptor antagonist. (18) In 12-week, multicenter, randomized, double-blind studies in adult patients with persistent asthma, treatment with montelukast ariseed in significant improvements in respiratory function, asthma symptoms, as-needed [[beta].sub.2]-agonist use, peripheral eosinophil esteems and health-related quality of life. (19-22) Furthermore, Pizzichini et al (23) demonstrated that 4 weeks of treatment with montelukast be deriveded in decreases in both sputum and peripheral relations eosinophils, suggesting that this medicine may exert anti-inflammatory actions in patients with asthma.

In this inquiry we investigated the effects of montelukast upon airway inflammation and airway hyperresponsiveness in patients with mild-to-moderate asthma in a randomized, double-blind, placebo-controlled, two-period crossover subject of attention Furthermore, the correlation between the decrease in sputum eosinophils and the increase in peak expiratory arise (PEF) was also evaluated.

...