Effects of pranlukast on aspirin-induced bronchoconstriction: differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients.
BACKGROUND
Aspirin inhibits cyclooxygenase activity and modifies production of the arachidonate cascade in aspirin-induced asthma. The aim of the present study was to examine the effects of leukotriene (LT) receptor antagonist on aspirin challenge on eosinophil activity and chemical mediators released into the airway of asthmatic patients.


METHODS
Aspirin oral provocation test was performed in aspirin-intolerant asthmatic patients (AIA; N = 7) and aspirin-tolerant asthmatic patients (ATA; N = 7). In AIA, LT receptor antagonist (pranlukast) was administered orally 2 hours before the test, and its inhibitory effects on sputum LTC4+C4, eosinophil cationic protein (ECP), eosinophil count, urinary LTE4/creatinine (Cr), 11-dehydrothromboxane (11-dhTX) B2/Cr, serum LTC4+D4, ECP, and peripheral blood eosinophil count were compared with the findings in ATA subjects.


RESULTS
In AIA, aspirin induced an immediate reaction associated with increased urinary LTE4/Cr and sputum ECP and a fall in urinary 11-dhTXB2/Cr. Pranlukast inhibited the bronchial reaction and an increase in sputum ECP after threshold dosed of ASA, but failed to change aspirin-induced LT production in sputum and urine. In ATA, aspirin challenge was only associated with a fall in urinary 11-dhTXB2.


CONCLUSIONS
Our results indicated that aspirin-induced asthma is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade and that leukotriene receptor antagonist are useful for AIA through inhibition of production of LT and eosinophilic inflammation in the airway.
Obase
Y
Y
Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Shimoda
T
T
Tomari
S
S
Mitsuta
K
K
Fukushima
C
C
Kawano
T
T
Matsuse
H
H
Kohno
S
S
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000139:chemically induced; D016084:Bronchoconstriction / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology* / Q000627:therapeutic use*; D004361:Drug Tolerance; D004804:Eosinophils / Q000166:cytology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D015289:Leukotrienes / Q000652:urine; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology
D002867:Chromones; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D001241:Aspirin; C047681:pranlukast