9-hydroxy-11-15-dioxo-2-3-18-19-tetranorprost-5-ene-1-20-dioic-acid and Asthma

We determined the effect of a long acting beta2-agonist, salmeterol, on aspirin-induced asthma (AIA) attacks and urinary release of eicosanoids in a double-blind, placebo-controlled, crossover study in 10 asthmatics sensitive to aspirin. The patients inhaled 50 microgram of salmeterol or placebo 15 min prior to a cumulative challenge with increasing doses of lysine-aspirin (L-ASA) (Part I), and before a single, predetermined dose of L-ASA that caused a 20% fall in FEV1 (PD20) (Part II). Salmeterol significantly attenuated aspirin-precipitated bronchoconstriction and the increase in urinary LTE4. Salmeterol also prevented the decrease in blood eosinophils, and abolished the correlation between the urinary levels of LTE4 and provocative doses of aspirin. In addition, PGD-M, the major urinary metabolite of PGD2, increased after L-ASA inhalation in six of nine subjects; this increase was blocked in all six by salmeterol. The protective effect of salmeterol on aspirin-induced attacks and mediator release suggests that it may be efficacious in aspirin-sensitive asthma.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Aspirin; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Cross-Over Studies; Cyclooxygenase Inhibitors; Double-Blind Method; Eicosanoids; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukotriene E4; Lysine; Male; Middle Aged; Placebos; Prostaglandin D2; Prostaglandins D; Salmeterol Xinafoate

1. A sensitive and specific negative ion chemical ionization mass spectrometric assay for the major urinary metabolite of PGD2 has been developed employing a chemically synthesized [18(0)4]-labelled internal standard. 2. The finding that increased urinary excretion of this metabolite occurs in a number of clinical situations suggests that the assay may prove to be a valuable tool to explore the role of PGD2 in the pathophysiology of human disease.

Topics: Asthma; Bronchoalveolar Lavage Fluid; Histamine; Humans; Hydroxyprostaglandin Dehydrogenases; Hypercholesterolemia; Indicator Dilution Techniques; Mass Spectrometry; Mastocytosis; Niacin; Prostaglandin D2; Prostaglandins D

Topics: Allergens; Asthma; Cyclooxygenase Inhibitors; Double-Blind Method; Forced Expiratory Volume; Hypersensitivity, Immediate; Indomethacin; Leukotriene E4; Mast Cells; Methylhistamines; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins D; Random Allocation; SRS-A