Circadian characteristics of urinary leukotriene E(4) in healthy subjects and nocturnal asthmatic patients.
OBJECTIVE
Circadian rhythmicity of cysteinyl leukotrienes (LTs) and thromboxane (TX)-A(2) in healthy subjects and nocturnal asthmatic patients remains a subject of controversy. The aim of this study was to investigate the contribution of these mediators to the pathogenesis of nocturnal asthma.


METHODS
We measured peak expiratory flow rate, urinary concentration of LTE(4), 11-dehydro-TXB(2), and creatinine eight times every 3 h in three groups: healthy control subjects (n = 5, group A), nocturnal asthmatic patients (n = 9, group B), and nonnocturnal asthmatic subjects (n = 9, group C). To evaluate the reproducibility of the measurement of urinary LTE(4), we measured urinary LTE(4) in group A for 3 separate days.


RESULTS
The urinary LTE(4) concentrations from 3 to 6 AM were significantly (p < 0.05) higher than from 3 to 6 PM in both group A and group B, but not in group C. The mean levels of LTE(4) in group B and group C were significantly higher (p < 0.05) than those in group A. In group B, another small peak was observed from 6 to 9 PM. No significant day-to-day variation was observed in group A. Urinary 11-dehydro-TXB(2) values from 3 to 6 AM were significantly (p < 0.001) higher than those levels from 3 to 6 PM in all groups, and the mean levels in group B and group C were significantly higher than those in group A (p < 0.05).


CONCLUSIONS
Circadian rhythmicity of urinary LTE(4) with a morning peak was found in healthy control subjects and nocturnal asthmatic subjects, but not in nonnocturnal asthmatic patients. It was suggested that cysteinyl LTs rather than TXA(2) might contribute to the nocturnal worsening of asthma.
Kurokawa
K
K
Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tanaka
H
H
Tanaka
S
S
Abe
S
S
D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000652:urine*; D002940:Circadian Rhythm / Q000502:physiology*; D003404:Creatinine / Q000652:urine; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D012016:Reference Values; D013928:Thromboxane A2 / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D003404:Creatinine