Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma.
Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinary leukotriene E4 (u-LTE4) in seven aspirin-sensitive subjects with asthma. Each subject performed two challenges with a single dose of LASA that caused a decrease in FEV1 of 20% or more in a preliminary test, immediately after inhaling 100 micrograms PGE2 in 4 ml saline or placebo, according to a randomized double-blind protocol. FEV1 was recorded at 30-min intervals for 4 h. u-LTE4 was measured by combined high-performance liquid chromatography enzyme immunoassay at 2-h intervals. After placebo, LASA caused an obstructive reaction in all patients, with a maximum decrease in FEV1 of 35 +/- 5% with respect to baseline. u-LTE4 rose from 911 +/- 261 picograms (pg)/mg creatinine at baseline to a maximum value of 2249 +/- 748 after challenge. Inhaled PGE2 provided almost complete protection in all patients. Baseline u-LTE4 was 883 +/- 243 pg/mg creatinine and did not change significantly during the test, reaching a maximum value of 864 +/- 290 (p < 0.05 versus placebo). These results confirm that PGE2 is highly effective in preventing aspirin-induced asthma and suggest that this effect is mediated by inhibition of sulfidopeptide leukotriene production.
Sestini
P
P
Institute of Respiratory Diseases, University of Siena, Italy.
Armetti
L
L
Gambaro
G
G
Pieroni
M G
MG
Refini
R M
RM
Sala
A
A
Vaghi
A
A
Folco
G C
GC
Bianco
S
S
Robuschi
M
M
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000009:adverse effects* / Q000031:analogs & derivatives; D001249:Asthma / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control* / Q000652:urine; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine; D008239:Lysine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged
D017999:Leukotriene E4; D008239:Lysine; D015232:Dinoprostone; D001241:Aspirin; C010395:acetylsalicylic acid lysinate