Bronchoconstrictor effects of leukotriene E₄ in normal and asthmatic subjects

The bronchoconstrictor activity of an aerosol of leukotriene E₄ (LTE₄) was compared with that of histamine in 5 normal and in 6 asthmatic subjects to define the relative potency of LTE₄ between the groups using 3 indices of airway response. The FEV₁ and the flow rate measured at 30% of vital capacity from partial and maximal expiratory maneuvers (V̇₃₀-P and V̇₃₀-M) were measured. The geometric mean (GSEM) concentration of LTE₄ required to reduce the V̇₃₀-P by 30% was 0.30 (1.46) mM in the normal subjects, and 0.058 (1.63) in the asthmatic subjects; LTE₄ was 39-fold more potent than histamine in the former and 14-fold in the latter group. Further, we observed that when normal and asthmatic subjects were compared at a degree of bronchoconstriction resulting in a 30% decrement in the V̇₃₀-P after inhaling LTE₄, there was a greater response in the asthmatic group than in the normal group of the accompanying change in the FEV₁. The decrements in the FEV₁ were not significantly different between the 2 groups after inhaling histamine. This study demonstrates that LTE₄ is a potent bronchoconstrictor agonist in humans and suggests that airway responsiveness to this agonist differs substantially with the index of bronchoconstriction used for assessment of airway response.