The challenge procedure influences the extent of allergen-induced urinary excretion of leukotriene E4

Background Cysteinyl-leukotrienes are central mediators in asthma and urinary leukotriene E-4 (LTE4) is a reliable marker of their endogenous formation. Objective This study tested the hypothesis that the procedure used for allergen bronchoprovocation influences the bronchoconstrictor response and the amount of LTE4 excreted following allergen challenge. Methods Seven atopic asthmatic men underwent two allergen bronchoprovocations 4 weeks apart. The same total dose of allergen was given at both sessions, cumulatively on one occasion and as a single dose at the other session. Urine was collected in hourly samples before and after challenge and LTE4 was measured with previously validated methodology. Results The mean (+/-SE) drop in FEV1 was not significantly different between the cumulative (29 +/- 2.4%) and the single dose challenge (25 +/- 2.8%). There was a significant increase in post-challenge levels of urinary LTE4 after both sessions. The peak excretion of LTE4 occurred Ih following the maximal drop in FEV1 for both challenges. However, the post-challenge increase in urinary LTE4 was significantly larger at the cumulative session. In fact, the net increase (post-challenge minus prechallenge:) of urinary LTE4 was more than twofold higher after the cumulative session (AUC 0-3h post-challenge: 46.7 +/- 8.2 vs 22.1 +/- 9.8, P < 0.05). Conclusion The peak excretion of urinary LTE4 occurred within 2 h after the termination of either challenge but the magnitude of urinary excretion of LTE4 was larger when cumulative challenge was performed. The findings are important to consider when designing studies where allergen-induced urinary excretion of LTE4 is an outcome variable.