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.

• Authors: P Sestini, L Armetti, G Gambaro, M G Pieroni, R M Refini, A Sala, A Vaghi, G C Folco, S Bianco, M Robuschi
• Journal: American 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
• PMID: 8564100 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Leukotriene E4
• Lysine
• Dinoprostone
• Aspirin
• acetylsalicylic acid lysinate

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