Salmeterol Prevents Aspirin-induced Attacks of Asthma and Interferes with Eicosanoid Metabolism

Abstract

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.

Prostaglandin D2: A dominant mediator of aspirin-exacerbated respiratory disease

“…Previous studies had reported that levels of PGD 2 metabolites in urine, plasma, or BAL fluid either remain unchanged 24,33,47,4 , or increase modestly with aspirin challenges in subjects with AERD 48 . The differences between these and our data likely reflect differences in sampling, the heterogeneous nature of AERD 49 , and the variable proportions of subjects with the phenotype defined by Group II.…”

Association of Four-locus Gene Interaction with Aspirin-intolerant Asthma in Korean Asthmatics

“…This model included four genotypes: B2ADR 46A>G, CCR3-520T>G, CysLTR1-634C>T, and FCER1B-109T>C. Of these four genes, the B2ADR 46A>G and CCR3-520T>G polymorphisms have been reported as being related to asthma [12][13][14] and the CysLTR1-634C>T and FCER1B-109T>C polymorphisms have been identified as significant genetic risk factors for developing AIA in the Korean population [7,23]. Moreover, B2ADR agonists (beta2 agonists and salmeterol) and CysLTR1 antagonists (montelukast and pranlukast) have been widely used to control asthma symptoms in the management of AIA patients [24,25]. Therefore, the best model suggested by MDR in this study is in agreement with the data from previous genetic association studies of AIA, which showed significant associations between SNPs and AIA in the Korean population.…”

Indirect airway challenges

“…Another pitfall that may produce false-negative aspirin provocation is indicated by observations that high doses of glucocorticosteroids may mask aspirin intolerance [203]. Moreover, it has been documented that treatment with antileukotrienes [96] and salmeterol [204] blunt the lysineaspirin induced airway response.…”