Exercise-Induced Urinary Excretion of Leukotriene E4 in Children with Atopic Asthma

Abstract

MATERIALS AND METHODSbeen suggested to have an important role not only in asthma but also in other diseases, such as neonatal persistent pulmonary hypertension and acute viral respiratory infections in children (6)(7)(8). However, little is known about the role of the sulfidopeptide LT in EIA. Arterial blood sampling is considered necessary to preclude the artificial formation of these sulfidopeptide LT (9), inasmuch as the high concentrations reportedly detected in plasma derived from venous blood are probably due to cellular injury during sample collection (9, 10). This seems to be an especially big problem in blood collection from infants and young children. Furthermore, the initial product of sulfidopeptide LT, LTC, is reportedly unstable even when stored at low temperatures (II), whereas LTE 4 is relatively more stable than LTC or LTD 4 in urine, even at 37°C (12). Therefore, to examine the role of these sulfidopeptide LT in EIA, we measured urinary LTE 4 concentrations before and after exercise in children with asthma of varying severities and explored the relationship of the urinary LTE4 concentration to the severity of asthma in EIA.Thirty-six children with a history of EIA, positive skin test to common allergens, and elevated IgE levels were entered into this study after informed consent was obtained. A control study with healthy children was not performed, because we could obtain informed consent from only a small number of healthy children and their parents. The children were classified as having either mild, moderate, or severe asthma, according to the criteria of the Japanese Research Group for Pediatric Allergy (Table 1). The classification of the patients was performed independently by other doctors unrelated to the measurement of urinary LTE 4 , before the urinary LTE 4 assay. The children with mild asthma could not produce enough urine for the assay. Urinary LTE 4 levels were measured in 10 children with severe asthma (age range: 7-12 y, mean: 9 y) and in seven children with moderate asthma (age range: 7-10 y, mean: 9 y), all of whom produced the required amount of urine (more than 60 mL) both before and after exercise. None of our subjects had used steroids or disodium chromoglycate for at least several months before the start of this investigation, with the exception of three children in the moderate asthma group who were using disodium chromoglycate. Subjects were asked to abstain from the intake of any medications for 12 h before the study.Exercise testing. Exercise was performed on a treadmill for 6 min with the speed set at 6.0 km/h and the incline set at a 10°. PEFR was measured using a peak flow meter (AS-SOO, Minato Medical Science, Osaka, Japan) before exercise and after exercise for up to 30 min. The best of three consecutive PEFR readings at each time point was used for subsequent analysis. All procedures were undertaken at ambient room temperature.Collection of urine samples. Subjects were asked to pass urine 2 h after exercise. Urine was actually collected from I to 2 h after exerc...

GC/MS analysis of urinary excretion of 9α,11β‐PGF2 in acute and exercise‐induced asthma in children

“…It was reported that there is no increase in the urinary excretion of LTE 4 up to 6 h following an exercise challenge in patients with EIA in whom there was a significant rise in urinary LTE 4 after an antigen challenge [18]. There is a significant rise in LTE 4 in children with EIA, but not in children with negative EIA [19]. Furthermore, in studies on the EIA inhibitory effects of intravenously administered MK571, which is a potent leukotriene D4‐receptor antagonist, one study prevented EIA [20], while another study did not prevent EIA [21].…”

Leukotrienes: Biosynthesis, Metabolism, and Pathophysiologic Significance

“…Lung diseases. In acute asthma, allergic rhinitis, and aspirinsensitive and exercise-induced asthma, elevated concentrations of LT have been recovered from biologic fluids, includingbronchoalveolar lavage, sputum, blood, and urine, spontaneously as well as after antigen challenge (43,(49)(50)(51)(52)(53) (Table 2). Clinical studies with LT receptor antagonists (see below) resulted in clinical improvement.…”

Assessment of thein vivo biochemical efficacy of orally active leukotriene biosynthesis inhibitors

“…However, the elucidation of peptide leukotriene metabolism in man [3][4][5], and the development of methodology to non-invasively measure increased in vivo 5-1ipoxygenase (5-LO) activity by monitoring elevations in levels of appropriate urinary metabolites [5][6][7], particularly LTE4 [6], has given increased credence to the hypothesis that peptidoleukotrienes are major mediators of asthmatic bronchoconstriction. Thus increased urinary LTE, excretion has been measured in acute asthma [7], antigen bronchoprovocation [6][7][8][9][10][11], aspirininduced asthma [12], exercise induced asthma [13] and nocturnal asthma [14]_ This major role for peptide LTs in asthma symptomology suggested by the above measurements of urinary LTE4 has recently been confirmed by the clinical efficacy of LTD4-receptor antagonists [15][16][17][18][19] in the above diseases. Similarly increased peptide leukotriene excretion (and a/so increased LTB4 biosynthesis in affected tissues) has been reported in a wide range of inflammatory conditions (affecting a variety of organs) such as cardiac ischemia [20,21], Adult Respiratory Distress [22][23][24], inflammatory bowel disease [25] and systemic lupus erythematosus [261.…”