High dose of inhaled fluticasone reduces high levels of urinary leukotriene E4 in the early morning in mild and moderate nocturnal asthma.
BACKGROUND
The circadian variation in urinary leukotriene E(4) (LTE(4)) excretion with a morning acrophase has recently been reported in nocturnal asthma (NA); however, the effects of inhaled corticosteroids (ICS) on this circadian rhythmicity of leukotriene (LT) in patients with NA are controversial.


METHODS
We first measured peak expiratory flow (PEF), urinary LTE(4), 11-dehydro-thromboxane B(2) (TXB(2)), and creatinine levels six times every 4 h for 24 h in two groups: patients with mild-to-moderate, steroid-naive NA (n = 10, group A), and patients with severe NA treated with high-dose ICS (n = 10, group B). Next, group A patients received 2 weeks of treatment with 800 microg/d of inhaled fluticasone propionate (FP), and we compared the measured parameters before and after treatment.


RESULTS
In group A, a circadian rhythm in urinary LTE(4) with peak levels at approximately 4 AM associated with reduced PEF was observed. Group B had suppression of urinary LTE(4) excretion and had no circadian rhythmicity, as seen in group A, despite a dip in PEF at 4 AM. A high dose of FP in group A significantly (p < 0.05) reduced LTE(4) levels and abolished the circadian rhythm, as well as improving PEF. We found no significant difference in the circadian rhythm of urinary 11-dehydro-TXB(2) between groups A and B, and high-dose FP partially decreased urinary 11-dehydro-TXB(2) levels but not significantly.


CONCLUSIONS
A high-dose of ICS reduced urinary LTE(4) levels and abolished their circadian variation in patients with asthma, suggesting that LT might contribute to the mechanism of NA.
Tanaka
Shintaro
S
Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tanaka
Hiroshi
H
Abe
Shosaku
S
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D002940:Circadian Rhythm; D003404:Creatinine / Q000652:urine; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D000730:Androstadienes; D005938:Glucocorticoids; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D003404:Creatinine; D000068298:Fluticasone