Format

Send to

Choose Destination
Am J Respir Crit Care Med. 1997 Dec;156(6):1725-30.

The leukotriene receptor antagonist zafirlukast inhibits sulfur dioxide-induced bronchoconstriction in patients with asthma.

Author information

1
Cardiovascular Research Institute, University of California, San Francisco, California 94143-0111, USA.

Abstract

Inhalation of sulfur dioxide (SO2) causes bronchoconstriction in most people with asthma. To examine the role of leukotrienes in this response, the antagonism of SO2-induced bronchoconstriction by a single oral dose of the leukotriene receptor antagonist zafirlukast was assessed in a double-blind, placebo-controlled, two-period crossover trial in 12 subjects with mild-to-moderate asthma. Subjects had bronchial hyperresponsiveness, an FEV1 < or = 70% of predicted, and a positive response to inhaled SO2 (an 8-unit increase in specific airway resistance on inhaling an SO2 concentration of < or = 4 ppm (PC8SRaw). Subjects were treated with zafirlukast (20 mg) or placebo on two treatment days 5 to 14 d apart. Two and 10 hours after treatment, subjects inhaled SO2 (0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 ppm) during eucapnic hyperventilation at 20 L/min. PC8SRaw was determined after each challenge. Blood samples were collected to assess zafirlukast plasma concentrations versus effect. PC8SRaw was significantly higher 2 h after zafirlukast compared with placebo (3.1 versus 1.5 ppm; p = 0.02) and remained higher 10 h after treatment with zafirlukast (2.7 versus 1.9 ppm; p = 0.09). An association was found between zafirlukast plasma concentrations and increases in PC8SRaw 10 h after treatment (p = 0.001). The safety profile of zafirlukast was not clinically different from placebo. A single 20-mg dose of zafirlukast attenuated SO2-induced bronchoconstriction. We conclude that S02-induced bronchoconstriction involves release of leukotrienes and that treatment with zafirlukast attenuates the bronchoconstrictor response.

PMID:
9412547
DOI:
10.1164/ajrccm.156.6.9608006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center