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(1)was 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.