Possible involvement of mast-cell activation in aspirin provocation of aspirin-induced asthma

Background: Although there is increasing evidence of the importance of cyst einyl leukotrienes (LT) as mediators of aspirin-induced bronchoconstriction in aspirin-sensitive asthma. the cellular origin of the LT is not yet clea r. Methods: Urinary concentrations of leukotriene E-4 (LTE4), 11-dehydrothromb oxane B-2, 9 alpha, 11 beta -prostaglandin F-2, and N-tau-methylhistamine w ere measured during the 24 h following cumulative intravenous administratio n of increasing doses of lysine aspirin to asthmatic patients. In addition, the urinary concentrations of these metabolites were measured on 5 consecu tive days in a patient who suffered an asthma attack after percutaneous adm inistration of nonsteroidal antiinflammatory drugs. Results: In aspirin-induced asthma patients (AIA, n = 10), the basal concen tration of urinary LTE4, but not the other metabolites, was significantly h igher than that in aspirin-tolerant asthma patients (ATA, n = 10). After in travenous aspirin provocation, the AIA group showed a 13. 1-fold (geometric mean) increase in excretion of LTE4 during the first 3 h, and 9 alpha, 11 beta -prostaglandin F-2 also increased in the AIA group during the first 0- 3 h and the 3-6 h collection period. N-tau-methylhistamine excretion was al so increased, but to a lesser degree. Administration of aspirin caused sign ificant suppression of 11-dehydrothromboxane B-2 excretion in both the AIA and ATA groups. When the percentage of maximum increase of each metabolite from the baseline concentrations was compared between the AIA group and the ATA group, a significantly higher increase in excretion of LTE4, 9 alpha, 11 beta -prostaglandin F-2, and N-tau-methylhistamine was observed in the A IA group than the ATA group. An increased excretion of LTE4 and 9 alpha, 11 beta -prostaglandin F-2 has been detected in a patient who suffered an ast hma attack after percutaneous administration of nonsteroidal anti-inflammat ory drugs. Conclusions: Considering that human lung mast cells are capable of producin g LTC4, prostaglandin D-2, and histamine, our present results support the c oncept that mast cells, at least, may participate in the development of asp irin-induced asthma.