title: High dose of inhaled fluticasone reduces high levels of urinary leukotriene E4 in the early morning in mild and moderate nocturnal asthma.
abstract: 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.
authors: Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Shintaro
authors: S
authors: Tanaka
authors: Hiroshi
authors: H
authors: Tanaka
authors: Shosaku
authors: S
authors: Abe
mesh_terms: 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
chemical_list: D000730:Androstadienes; D005938:Glucocorticoids; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4; D003404:Creatinine; D000068298:Fluticasone