Background: The circadian variation in urinary leukotriene E4 (LTE4) 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 LTE4, 11-dehydro-thromboxane B2 (TXB2), 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 μg/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 LTE4 with peak levels at approximately 4 am associated with reduced PEF was observed. Group B had suppression of urinary LTE4 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 LTE4 levels and abolished the circadian rhythm, as well as improving PEF. We found no significant difference in the circadian rhythm of urinary 11-dehydro-TXB2 between groups A and B, and high-dose FP partially decreased urinary 11-dehydro-TXB2 levels but not significantly.
Conclusions: A high-dose of ICS reduced urinary LTE4 levels and abolished their circadian variation in patients with asthma, suggesting that LT might contribute to the mechanism of NA.