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Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma.

Abstract
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.
AuthorsP Sestini, L Armetti, G Gambaro, M G Pieroni, R M Refini, A Sala, A Vaghi, G C Folco, S Bianco, M Robuschi
JournalAmerican journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 153 Issue 2 Pg. 572-5 (Feb 1996) ISSN: 1073-449X [Print] UNITED STATES
PMID8564100 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • acetylsalicylic acid lysinate
  • Leukotriene E4
  • Lysine
  • Dinoprostone
  • Aspirin
Topics
  • Administration, Inhalation
  • Adolescent
  • Adult
  • Aspirin (adverse effects, analogs & derivatives)
  • Asthma (chemically induced, physiopathology, prevention & control, urine)
  • Bronchial Provocation Tests
  • Bronchoconstriction (drug effects)
  • Chromatography, High Pressure Liquid
  • Dinoprostone (administration & dosage)
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Leukotriene E4 (urine)
  • Lysine (analogs & derivatives)
  • Male
  • Middle Aged

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