The relative responsiveness to inhaled leukotriene E4, methacholine and histamine in normal and asthmatic subjects.
The relative bronchoconstricting potencies of leukotriene E4 (LTE4) methacholine and histamine have been compared in asthmatic and normal subjects. LTE4 responsiveness in asthmatic subjects, as measured by the dose which produced a 35% fall in specific airways conductance (PD35), ranged from 0.06-24.4 nmol (geom mean 4.1 nmol, n = 20). This was significantly less than the PD35 in normal subjects (range 39.0-370 nmol, geom mean 105 nmol, n= 6; p less than 0.001). There was a correlation between LTE4 and methacholine responsiveness (r = 0.84, p less than 0.001) and between LTE4 and histamine responsiveness (r = 0.79, p less than 0.001). LTE4 was 73 times more potent than methacholine and 112 times more potent than histamine in asthmatic subjects. LTE4 was 20 times more potent than methacholine and 58 times more potent than histamine in normal subjects. LTE4 is a potent bronchoconstrictor agent, and LTE4 responsiveness correlates with both histamine and methacholine responsiveness.
O'Hickey
S P
SP
Department of Medicine, United Medical School, Guy's Hospital, London, U.K.
Arm
J P
JP
Rees
P J
PJ
Spur
B W
BW
Lee
T H
TH
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects*; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D017999:Leukotriene E4; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology
D008688:Methacholine Compounds; D013189:SRS-A; D016210:Methacholine Chloride; D017999:Leukotriene E4; D006632:Histamine