Possible involvement of mast-cell activation in aspirin provocation of aspirin-induced asthma.
BACKGROUND
Although there is increasing evidence of the importance of cysteinyl leukotrienes (LT) as mediators of aspirin-induced bronchoconstriction in aspirin-sensitive asthma, the cellular origin of the LT is not yet clear.


METHODS
Urinary concentrations of leukotriene E4 (LTE4), 11-dehydrothromboxane B2, 9alpha,11beta-prostaglandin F2, and Ntau-methylhistamine were measured during the 24 h following cumulative intravenous administration of increasing doses of lysine aspirin to asthmatic patients. In addition, the urinary concentrations of these metabolites were measured on 5 consecutive days in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs.


RESULTS
In aspirin-induced asthma patients (AIA, n=10), the basal concentration of urinary LTE4, but not the other metabolites, was significantly higher than that in aspirin-tolerant asthma patients (ATA, n=10). After intravenous aspirin provocation, the AIA group showed a 13.1-fold (geometric mean) increase in excretion of LTE4 during the first 3 h, and 9alpha,11beta-prostaglandin F2 also increased in the AIA group during the first 0-3 h and the 3-6 h collection period. Ntau-methylhistamine excretion was also increased, but to a lesser degree. Administration of aspirin caused significant suppression of 11-dehydrothromboxane B2 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, 9alpha,11beta-prostaglandin F2, and Ntau-methylhistamine was observed in the AIA group than the ATA group. An increased excretion of LTE4 and 9alpha,11beta-prostaglandin F2 has been detected in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs.


CONCLUSIONS
Considering that human lung mast cells are capable of producing LTC4, prostaglandin D2, and histamine, our present results support the concept that mast cells, at least, may participate in the development of aspirin-induced asthma.
Mita
H
H
Clinical Research Center, National Sagamihara Hospital, Japan.
Endoh
S
S
Kudoh
M
M
Kawagishi
Y
Y
Kobayashi
M
M
Taniguchi
M
M
Akiyama
K
K
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000652:urine; D001985:Bronchial Provocation Tests / Q000379:methods*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015237:Dinoprost / Q000652:urine; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008761:Methylhistamines / Q000652:urine; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013928:Thromboxane A2 / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D008761:Methylhistamines; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D015237:Dinoprost; D001241:Aspirin