Clinical and genetic features underlying the response of patients with bronchial asthma to treatment with a leukotriene receptor antagonist.

Abstract

Treatment with antileukotriene drugs results in clinical improvement in many, though not all, patients with asthma. It can be hypothesized that the subpopulation of asthmatic patients, characterized by aspirin intolerance and cysteinyl-leukotriene overproduction, might profit most from antileukotriene treatment. We compared the clinical response to montelukast in two well-matched groups of patients with mild asthma: 26 aspirin-intolerant asthmatics (AIAs) and 33 aspirin-tolerant asthmatics (ATAs). We also searched for possible predictors of the clinical response among the parameters reflecting the expression and production of cysteinyl-leukotrienes (cys-LTs). This was an 8-week, single-blind, placebo-controlled trial. Following a 3-week montelukast 10 mg day-1 treatment compared with placebo, there was a statistically significant reduction in the mean daytime and nocturnal asthma symptoms and beta 2-agonist use, as well as a significant improvement in the morning and evening peak expiratory flows and quality of life. Both groups showed a similar significant improvement in the parameters studied. Clinical response did not correlate with the baseline urinary LTE4 excretion level. Improvement of asthma was observed mostly in patients with a low baseline and non-IL-5 inducible expression of LTC4 synthase (LTC4S) mRNA in eosinophils. There was a trend toward a better response in carriers of LTC4S allele C, but no relationship to the CC10 genetic polymorphism. No difference in the clinical response to the montelukast treatment was observed between the AIAs and the ATAs.