Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthma

J Allergy Clin Immunol. 1995 Nov;96(5 Pt 1):643-51. doi: 10.1016/s0091-6749(95)70263-6.


Background: Leukotriene E4 (LTE4) and histamine excreted into the urine reflect the in vivo synthesis and release of cysteinyl leukotrienes and histamine, respectively. We examined the diurnal variation of the excretion rate of these mediators over 4 consecutive days in normal subjects (n = 5) and patients with stable mild-to-moderate asthma (n = 8).

Methods: Sixteen consecutive 6-hour urine samples were collected over 4 days. Urinary LTE4 concentrations were determined by reverse-phase high-pressure liquid chromatography, followed by ELISA. Urinary histamine concentrations were measured by ELISA. The excretion rates of these compounds were normalized relative to urinary creatinine content.

Results: The mean urinary LTE4 excretion rate was 83.8 +/- 38.2 pg/mg creatinine (mean +/- SD) in normal subjects; in patients with asthma, the urinary LTE4 excretion rate (110.0 +/- 59.2 pg/mg creatinine) was significantly higher than that in normal subjects (p < 0.05). The urinary histamine excretion rate was not different between normal subjects (24.0 +/- 12.5 ng/mg creatinine) and patients with asthma (31.5 +/- 25.8 ng/mg creatinine). A robust and systematic within-day variation (p < 0.01), but no day-to-day variation, was observed in histamine excretion rate. Although the magnitude of variation in LTE4 excretion within a day was significantly greater in patients with asthma than in normal subjects (p < 0.05), we could not identify any specific diurnal variation pattern in either the normal or the asthma group. No significant correlation was observed between urinary LTE4 and histamine excretion rate within any subject.

Conclusions: Patients with asthma excrete LTE4 in the urine at a greater rate than normal subjects. Although no systematic variation in urinary LTE4 excretion rates over the course of a day was observed in either normal subjects or patients with stable asthma, the presence of a systematic diurnal variation of urinary histamine excretion exists in both groups.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Asthma / complications
  • Asthma / urine*
  • Chromatography, High Pressure Liquid
  • Circadian Rhythm*
  • Creatinine / urine
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Histamine / urine*
  • Humans
  • Leukotriene E4 / urine*
  • Male
  • Middle Aged


  • Leukotriene E4
  • Histamine
  • Creatinine