Bronchodilator effect of zafirlukast in subjects with chronic obstructive pulmonary disease

Abstract

Cysteinyl leukotrienes (LT) are involved in airway inflammation and mucus hypersecretion, characteristically present in asthma and chronic obstructive pulmonary disease (COPD). Zafirlukast is an LT receptor antagonist that improves airway function within 1–3 h after oral administration in subjects with chronic persistent asthma. Through a randomised, double-blind, crossover and placebo-controlled study, we assessed the short-term effects of zafirlukast in patients with severe COPD. We enrolled 23 subjects (seven women) aged 59.4 (1.67) yr [mean (SEM)] with a smoking history of 60.7 (5.2) pack-yr. At screening day the mean FEV 1was 0.876 (0.72) l; FEV 1 % predicted=35 (3)% and 107 (14) ml increment post-salbutamol. They came two different days, apart from each other at least 72 h. After baseline spirometry, a single oral dose of 40 mg zafirlukast or the corresponding placebo was administered. FVC and FEV 1 was measured every 30 min until 2 hrs. On zafirlukast day, the mean FEV 1 at 90 min [0.813 (0.64) l] and the mean FVC at 90 min [1.76 (0.1) l] were significantly higher than the respective means at placebo day (mean FEV 1=0.747 (0.55) l; mean FVC=1.63 (0.1) l; p<0.05 Tukey Kramer multiple comparisons test). The maximum mean increase in FEV 1 was 75 (19) ml. A positive correlation was found between absolute response to salbutamol in FEV 1 and the response to zafirlukast ( r=0.41; p<0.04). In conclusion, these findings suggest that zafirlukast has a bronchodilator or antibronchoconstrictor effect in COPD patients with severe airflow limitation.