Urinary leukotriene E₄ levels during early and late asthmatic responses

The sulphidopeptide leukotrienes C₄ and D₄ (LTC₄, LTD₄) are protent bronchoconstrictor mediators, released from human lung fragments after challenge with specific allergens in vitro. The purpose of this study was to measure urinary LTE₄ (metabolite of LTC₄ and LTD₄) in subjects undergoing inhalation challenges with allergens or occupational sensitizing agents in the laboratory. Eighteen subjects with previously documented isolated early asthmatic responses (EARs), isolated late asthmatic responses (LARs), or dual (both early and late) asthmatic responses were studied. Urinary LTE₄ levels increased in subjects who developed either isolated EARs (mean fall in FEV₁, 27.98%) or early responses preceding LARs (mean fall in FEV₁, 15.01%). The baseline levels of LTE₄ were 150.26 (SEM, 49.5) pg/mg of creatinine in the isolated responders and 66.60 (SEM, 13.5) pg/mg of creatinine in the dual responders. These levels increased to 1816 (SEM, 606.1) pg/mg of creatinine (p=0.041) and 174.80 (SEM, 40.1) pg/mg of creatinine (p=0.025), respectively, after the EAR. The degree of maximal bronchoconstriction during the EAR correlated with the levels of LTE₄ (r=0.68; p=0.001). No significant increase in urinary LTE₄ levels occurred during the LAR. These results suggest that the LTE₄ precursors, LTC₄ and LTD₄, are important bronchoconstrictor mediators causing EARs after allergen inhalation.