Increased urinary LTE4 excretion following inhalation of LTC4 and LTE4 in asthmatic subjects.
Urinary leukotriene E4 (LTE4) increases during exacerbations of asthma and following antigen challenge. We determined whether urinary LTE4 excretion reflects sulphidopeptide leukotrienes in the airways of asthmatic patients. Urinary LTE4 concentration was measured prior to and 1.5 and 3.5 h following inhalation of bronchoconstrictive doses of leukotriene C4 (LTC4) or LTE4 in eight asthmatic subjects. Increasing doses of agonist were inhaled until a 35% fall in specific airways conductance (sGaw) was achieved. There was no significant difference between the 53 +/- 3% (mean +/- SEM) fall in sGaw following inhalation of LTC4 (63.1 ng geometric mean, GM, range 5.8-527.5 ng) and the 43 +/- 4% fall in sGaw following inhalation of LTE4 7.94 ng/GM (range 132-3701 ng). The LTE4 excretion rate increased significantly from 2.95 (range 0.6-17.5) ng.h-1 to 4.67 (range 0.8-20) ng.h-1 at 1.5 h following LTC4 inhalation; and from 1.8 (range 0.07-6.7) ng.h-1 to 6.9 (range 2.9-27.3) ng.h-1 at 1.5 h following LTE4 inhalation; and had returned from baseline by 3.5 h. There was a correlation between the dose of LTC4 inhaled and LTE4 excreted in the urine (r = 0.82 and r = 0.72, respectively). The % recovery of LTE4 in the urine, of the total dose of inhaled LTC4 or LTE4 administered, was 6.9 +/- 4.1% and 0.8 +/- 0.3%, respectively. Thus, inhalation of bronchoconstricting doses of LTC4 or LTE4 alter urinary LTE4 excretion in a dose-dependent fashion. This indicates that urinary LTE4 can be used as a marker of sulphidopeptide leukotriene synthesis in the lungs of patients with asthma.
Christie
P E
PE
Swiss Institute for Allergy and Asthma Research, Davos.
Tagari
P
P
Ford-Hutchinson
A W
AW
Black
C
C
Markendorf
A
A
Schmitz-Schumann
M
M
Lee
T H
TH
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000378:metabolism*; D005260:Female; D006801:Humans; D017997:Leukotriene C4 / Q000008:administration & dosage / Q000378:metabolism*; D017999:Leukotriene E4 / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine*; D008297:Male; D008875:Middle Aged
D017997:Leukotriene C4; D017999:Leukotriene E4