Early increase in urinary leukotriene E4 (LTE4) is dependent on allergen dose inhaled during bronchial challenge in asthmatic subjects

Background: Urinary leukotriene E-4 (LTE4) excretion is a good marker of the rate of total body production of sulfidopeptide leukotrienes released during allergen challenge. Methods: Twenty-three subjects with allergic asthma were challenged with inhaled allergen, and the urinary excretion of LTE4 was determined by immunoenzymatic assay (associated with HPLC separation) at various intervals after challenge. Results: Allergen challenge caused an early airway response (EAR) with a drop in FEV1 of 40.3+/-9.9%. This was associated with an increase in urine LTE4 excretion for 0-3 h after allergen inhalation (296+/-225.25 pg/mg creatinine) in comparison with baseline values obtained during the night before challenge (101.02+/-61.97 pg/mg creatinine). Urinary LTE4 excretion was significantly higher in subjects who inhaled a higher dose of allergen during challenge (LTE4 during EAR: 211+/-192 pg/mg creatinine in subjects with inhaled total dose of allergen <0.1 biologic units; 408+/-223 pg/mg creatinine in subjects with inhaled total dose >0.1 biologic units). All subjects showed a late airway response (LAR) to allergen of different severity, from mild (FEV1 fall: 15-20%) to severe (>30%); no correlation was found between the increase in urine LTE4 excreted during LAR (3-7 h after challenge) and the severity of LAR, but only subjects with severe LAR showed a significant increase in LTE4 during LAR in comparison with baseline value. Conclusions: A release of sulfidopeptide leukotrienes, as evaluated by urinary LTE4 excretion, can be documented during EAR and LAR to allergen in relation to the dose of inhaled allergen, and it can represent a useful index of the events underlying the airway inflammatory responses during allergen challenge.