Salmeterol prevents aspirin-induced attacks of asthma and interferes with eicosanoid metabolism.
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.
Szczeklik
A
A
Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland.
Dworski
R
R
Mastalerz
L
L
Prokop
A
A
Sheller
J R
JR
Nizankowska
E
E
Cmiel
A
A
Oates
J A
JA
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D015777:Eicosanoids / Q000378:metabolism* / Q000652:urine; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine; D008239:Lysine / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D015230:Prostaglandin D2 / Q000652:urine; D011457:Prostaglandins D / Q000652:urine; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D010919:Placebos; D011457:Prostaglandins D; D000068299:Salmeterol Xinafoate; C035860:9-hydroxy-11,15-dioxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid; D017999:Leukotriene E4; D008239:Lysine; D000420:Albuterol; D001241:Aspirin; D015230:Prostaglandin D2