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 (V30-P and V30-M) were measured. The geometric mean (GSEM) concentration of LTE4 required to reduce the V30-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 V30-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.
D000336:Aerosols; D001249:Asthma / Q000503:physiopathology*; D001986:Bronchial Spasm / Q000139:chemically induced* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D017999:Leukotriene E4; D008297:Male; D008448:Maximal Expiratory Flow Rate; D009994:Osmolar Concentration; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014797:Vital Capacity
D000336:Aerosols; D013189:SRS-A; D017999:Leukotriene E4; D006632:Histamine