Bronchial hyperresponsiveness, hypersensitivity to analgesics and urinary leukotriene E4 excretion in patients with aspirin-intolerant asthma.
This study was designed to investigate the protective effect of cromolyn sodium on airway sensitivity to sulpyrine, and bronchial responsiveness to methacholine, and to investigate whether this protective activity is associated with reduction in aspirin-induced excretion of urinary leukotriene E4 (u-LTE4), a marker of the cysteinyl LT overproduction that participates in the pathogenesis of aspirin-induced asthma. We assessed the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to a sulpyrine provocation test were included in this study. A double-blind, randomized, crossover design was used. u-LTE4 was measured using combined reverse-phase high-performance liquid chromatography enzyme immunoassay. Cromolyn sodium protected against analgesic-induced bronchoconstriction through mechanisms that are not related to its bronchodilator property, but to the improvement of both bronchial hyperresponsiveness and hypersensitivity to analgesics (p<0.01 and p<0.001). Although excretion of u-LTE4 did not increase after the methacholine provocation test, it significantly increased after sulpyrine provocation (p<0.01). Furthermore, after pretreatment with cromolyn sodium, the maximum level of u-LTE4 after the sulpyrine provocation test was significantly lower than in controls (p<0.01). These results support the hypothesis that cysteinyl LT is one of the most important components in the pathogenesis of aspirin-intolerant asthma. Cromolyn sodium improves both hypersensitivity to analgesics, and bronchial hyperresponsiveness in aspirin-intolerant asthma.
Institute for Comprehensive Medical Sciences, Fujita Health University School of Medicine, Toyoake, Japan. syoshida@nisiq.net
S
S
Yoshida
H
H
Nakagawa
Y
Y
Yamawaki
H
H
Sakamoto
K
K
Akahori
M
M
Nakabayashi
M
M
Sakamoto
H
H
Hasegawa
T
T
Shoji
T
T
Tajimab
H
H
Amayasu
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000517:prevention & control / Q000652:urine*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000517:prevention & control / Q000652:urine*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004205:Cromolyn Sodium / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004177:Dipyrone; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged
D018927:Anti-Asthmatic Agents; D016210:Methacholine Chloride; D004177:Dipyrone; D017999:Leukotriene E4; D004205:Cromolyn Sodium; D001241:Aspirin