Effects of pranlukast, a cysteinyl leukotriene antagonist, on bronchial responsiveness to methacholine in aspirin-intolerant asthmatics treated with corticosteroids.
Cysteinyl leukotrienes (cysLTs) are considered to be the most important mediator involved in the pathogenesis of aspirin-intolerant asthma (AIA). However, the role of cysLTs in the baseline condition of the pathophysiology of AIA when not exposed to non-steroidal antiinflammatory drugs (NSAIDs) as well as that in the pathophysiology of aspirin-tolerant asthma remains to be elucidated. Therefore, we evaluated the effect of pranlukast, a potent, selective cysLT receptor antagonist, on bronchial responsiveness to methacholine, a non-specific stimulus, in 7 well-controlled aspirin-intolerant asthmatics receiving oral or inhaled corticosteroid treatment. Pranlukast was orally administered at a dose of 225 mg twice daily to all patients for 4 weeks, and the methacholine challenge test was performed before and after pranlukast treatment. The methacholine provocative concentration producing a 20% fall in forced expiratory volume in 1 second (PC20-FEV1) was calculated as an index of bronchial hyperresponsiveness (BHR). The geometric mean values of PC20-FEV1 significantly (p = 0.028) increased from 0.34 mg/dl to 0.61 mg/dl after pranlukast treatment. No significant differences were observed in the baseline values of forced vital capacity (FVC) or FEV1 before and after pranlukast treatment. These findings suggest that antagonism of endogenous cysLT by pranlukast may be responsible for the improvement of BHR to methacholine.
Ishioka
S
S
Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Hozawa
S
S
Haruta
Y
Y
Maeda
A
A
Tamagawa
K
K
Watanabe
T
T
Hiyama
K
K
Yamakido
M
M
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D002867:Chromones / Q000494:pharmacology*; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged
D000305:Adrenal Cortex Hormones; D002867:Chromones; D020024:Leukotriene Antagonists; D016210:Methacholine Chloride; D001241:Aspirin; C047681:pranlukast