URINARY LEUKOTRIENE-E4 IN PATIENTS WITH ASTHMA - EFFECT OF AIRWAYS REACTIVITY AND SODIUM CROMOGLYCATE

A group of 17 patients with allergic asthma was challenged with aerosolized antigen, and the excretion of the peptidoleukotriene metabolite leukotriene (LT) E4 in the urine was determined as an index of leukotriene synthesis. The allergen challenge caused a drop in FEV1 of 25 to 59% within the first 2 h in all patients. This was associated with an increase in urine LTE4 excretion during the subsequent 12 h. The amount of urinary LTE4 excreted increased from a 12-h baseline level of 46 +/- 6.8 ng to a postallergen challenge level of 92 +/- 13 ng. In a similar experimental protocol methacholine challenge alone did not significantly increase urinary LTE4 excretion. In comparing all individuals as a group, there was no significant positive correlation between the magnitude of the drop in FEV1 during the immediate asthmatic response (IAR) and the increased amount of LTE4 excreted in the urine (p = 0.08). These parameters were still not significantly correlated when airways reactivity (log PC20) was also considered (p = 0.057). However, when each individual was compared to self in the presence and absence of cromoglycate, a significant correlation was found to exist between the drop in FEV1 during the IAR, the excretion of urinary LTE4, and the airways reactivity. No correlation was found between the increase in urine LTE4 excreted during the 12 h following allergen challenge and the severity of late (3 to 12 h) responses to allergen, but there was a significant prolonged (12 to 36 h) elevated urine LTE4 excretion in those patients with the most severe late asthmatic response. These results suggest that leukotriene synthesis in the airways is increased during allergic asthmatic reactions and this increased synthesis may mediate some of the symptoms observed.