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(Chest. 2003;124:1768-1773.)
© 2003 American College of Chest Physicians

High Dose of Inhaled Fluticasone Reduces High Levels of Urinary Leukotriene E4 in the Early Morning in Mild and Moderate Nocturnal Asthma*

Shintaro Tanaka, MD; Hiroshi Tanaka, MD and Shosaku Abe, MD

* From the Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

Correspondence to: Hiroshi Tanaka, MD, Third Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku Sapporo 060-8543, Japan; e-mail: tanakah{at}sapmed.ac.jp

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.

Key Words: circadian rhythm • inhaled corticosteroid • leukotriene • nocturnal asthma






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