leukotriene-e4 and Asthma--Exercise-Induced

To remind readers that evaporative water loss from the airway surface is the stimulus for exercise-induced bronchoconstriction. To emphasize that recruitment of the peripheral airways determines severity of exercise-induced bronchoconstriction. To draw attention to the potential for injury of the epithelium and for plasma exudation to contribute to the pathogenesis of exercise-induced bronchoconstriction in athletes. To emphasize that many inflammatory mediators are involved in exercise-induced bronchoconstriction and that some are found in both asthmatic and healthy subjects.. That inflammatory mediators are released into the airways in response to exercise and can be measured by inducing sputum (histamine, cysteinyl leukotrienes) or collecting condensate from exhaled air (cysteinyl leukotrienes and adenosine). The concentration of mediators was reduced in response to a combination of loratadine and montelukast. Exercise is a stimulus for upregulating the genes coding for the 5-lipoxygenase pathway in healthy subjects.. Dehydration of the airways results in release of mediators. The likely source of these mediators is the mast cell. Epithelial injury occurs in exercise-induced bronchoconstriction. The process of repair may contribute to the development of airway hyperresponsiveness in healthy subjects. Measuring the airway response to exercise, or a surrogate for exercise, as an indicator of airway hyperresponsiveness is warranted in patients with symptoms of asthma.

Topics: Asthma, Exercise-Induced; Bronchoconstriction; Dinoprost; Humans; Inflammation Mediators; Leukotriene E4; Mast Cells

Conjugated linoleic acid (CLA) has been reported to modify the inflammatory response associated with allergic airway disease, primarily in animal models. To extend these observations to humans, the effect of short-term CLA supplementation on the severity of exercise-induced bronchoconstriction (EIB) was investigated in asthmatics.. Six subjects with physician-diagnosed asthma and EIB began the study on their usual diet, to which was added 4.8 g CLA/d for 8 wk. Pulmonary-function tests were administered before and after eucapnic voluntary hyperventilation (EVH) challenge at the commencement (Week 0) and conclusion of the treatment period (Week 8). Pre- and 90 min post-EVH challenge, urine was assayed for the presence of cysteinyl leukotrienes (LT) C4-E4 and 9α, 11β-prostaglandin (PG) F2.. Pre- to post-EVH forced expiratory volume in 1 s (FEV1) did not significantly differ (p > .05) from Week 8 to Week 0. The pre- to post-EVH decline in FEV1 at Week 8 (-29.6% ± 6.6%) was not significantly different (p > .05) from that at Week 0 (-32.0% ± 5.5%). Area under the curve of FEV1 plotted against time from zero to 60 min (AUC0-60) was unaltered at Week 8 (-931% ± 350% change per minute) compared with Week 0 (-1,090% ± 270% change per minute). CLA supplementation did not alter forced midexpiratory flow, forced vital capacity (FVC), or FEV1/FVC. In addition, post-EVH urinary LTC4-E4 and 9α, 11β-PGF2 were unchanged after CLA supplementation.. Daily supplementation of 4.8 g CLA for 8 wk does not attenuate airway inflammation or hyperpnea-induced bronchoconstriction in asthmatic individuals.

Topics: Adolescent; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Biomarkers; Bronchoconstriction; Dietary Supplements; Dinoprost; Female; Humans; Leukotriene C4; Leukotriene E4; Linoleic Acids, Conjugated; Male; Respiratory Function Tests; Respiratory Rate; Young Adult

The role of mast cells in the airway response to exercise and the benefit of sodium cromoglycate (SCG) in athletes are unclear.. The purpose of this study was to clarify the role of mast cell mediators in the airway response to exercise in athletes and to investigate the effect of SCG.. Eleven athletes with exercise-induced bronchoconstriction (EIB+) and 11 without (EIB-) performed a eucapnic voluntary hyperpnea (EVH) test (a surrogate for exercise) 10 min after inhalation of a placebo or 40 mg of the mast cell stabilizing agent sodium cromoglycate. The urinary concentrations of 9a,11β-PGF2 (a metabolite of PGD2 and a marker of mast cell activation) and leukotriene E4 (LTE4) were measured by enzyme immunoassay 60 min before and for 90 min after the challenge.. In the EIB+ group, the maximum fall in forced expiratory volume in 1 s (FEV1) of 20.3% ± 3% on placebo was reduced to 11.5% ± 1.9% after SCG (P = 0.003). There was an increase in the urinary excretion of 9α,11β-PGF2 on the placebo day after EVH in both groups (P < 0.05) that was abolished by SCG. In the EIB+ group, there was also an increase of urinary LTE4 on the placebo day that was abolished by SCG, whereas the urinary excretion of LTE4 was inconsistent in the EIB- group.. The results support mast cell activation with release of bronchoconstrictive mediators after hyperpnea in athletes with and without EIB and inhibition by SCG. The degree of airway responsiveness to the specific mediator released is likely to determine whether or not bronchoconstriction will occur after EVH.

Topics: Adrenergic Agonists; Adult; Androstadienes; Asthma, Exercise-Induced; Athletes; Bronchodilator Agents; Cromolyn Sodium; Dinoprost; Exercise Test; Female; Fluticasone; Forced Expiratory Volume; Humans; Hyperventilation; Inflammation Mediators; Leukotriene E4; Male; Mast Cells; Young Adult

Montelukast, a cysteinyl-leukotriene receptor antagonist, was reported to have a protective effect against exercise-induced bronchoconstriction (EIB). Aspirin-induced asthma (AIA) is characterized by overproduction of cysteinyl-leukotrienes.. The aim of the study was to compare the response to exercise and the effect of montelukast on EIB in AIA as compared to aspirin-tolerant asthma (ATA).. A placebo-controlled, double blind, cross-over randomized study was performed in 19 AIA and 21 ATA patients with stable asthma. A single dose of montelukast (10 mg) or placebo (PL), was given orally one hour prior to exercise challenge. FEV1 was measured before and 5, 10, 15 min after exercise and then at 15-minute intervals for 4 h. Urinary LTE4 excretion and blood eosinophil count were measured at baseline, 2 h and 4 h following exercise challenge.. Positive bronchial response to exercise was observed in 47.5% of all patients studied. Exercise led to almost identical maximal fall in FEV1 in AIA and ATA patients (23.5% +/- 6.8% vs. 21.8% +/- 12.0%, respectively; P = 0.7). Montelukast, as compared to PL, significantly attenuated EIB in 63.2% of 19 patients with positive exercise test preceded by PL. The mean of maximum fall in FEV1 from the pre-exercise value was 10.2% +/- 13.8 after montelukast as compared to 22.5% +/- 10.2 after placebo (P < 0.001). No significant differences between protective effect of montelukast was observed in AIA as compared to ATA patients (P = 0.63, anova). Urinary LTE4 excretion showed no change following exercise, irrespective of the result of the test in all subjects.. Patients with AIA and ATA react similarly to exercise challenge and obtain similar protection against EIB by montelukast.

Topics: Acetates; Adult; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma, Exercise-Induced; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Hypersensitivity; Exercise Test; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene E4; Lung; Male; Middle Aged; Quinolines; Sulfides

The novel 5-lipoxygenase (5-LO) inhibitor, ABT-761, was investigated for its effect on exercise-induced bronchoconstriction in asthmatic subjects. The relationship between 5-LO inhibition and effects on the response of the airways to exercise was examined. In a double-blind, randomized, crossover clinical trial, 10 patients with mild to moderate persistent asthma (who exhibited a fall in forced expiratory volume in one second (FEV1) > or = 20% following standardized exercise challenge) received 200 mg ABT-761 or matched placebo, orally, 5 h prior to exercise on two study days, 7-10 days apart. Lung function, urinary leukotriene E4 (LTE4) and ex vivo calcium ionophore-stimulated LTB4 release in whole blood were measured prior to dosing, prior to exercise and at various time points up to 4 h post-exercise. The mean (SD) maximal percentage fall in FEV1 after exercise was 27.1 (12)% on placebo and 19.9 (10)% on ABT-761 days, respectively (p<0.05). Post-exercise fall in FEV1 was significantly attenuated at 5, 10, 15 and 30 min after exercise and the mean area under curve, representing the overall effect of exercise from 0-45 min post-challenge, was also significantly attenuated by ABT-761 (p<0.001). Ex vivo LTB4 release was inhibited by more than 80% throughout the 4 h post-exercise period, indicating that 5-LO was extensively inhibited at all time points. Urinary LTE4 in the post-exercise period was significantly lower after ABT-761 day than after placebo (40.1 (17.6) versus 89.8 (58.2) pg x mg creatinine(-1); p<0.05). Inhibition of LTB4 release in ABT-761-treated patients correlated positively with the attenuation of post-exercise FEV1 decline (r=0.711; p<0.05). We conclude that ABT-761 is effective in suppressing exercise-induced bronchoconstriction and that this protection is related quantitatively to the degree of 5-lipoxygenase inhibition.

Topics: Adult; Asthma, Exercise-Induced; Bronchoconstriction; Cross-Over Studies; Double-Blind Method; Enzyme Inhibitors; Exercise Test; Female; Humans; Hydroxyurea; Leukotriene E4; Lipoxygenase Inhibitors; Male

A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated.. Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall in FEV1 after exercise of at least 20% were enrolled. Subjects received placebo and montelukast 100 mg once daily in the evening or 50 mg twice daily, each for two days, in a three-period, randomised, double blind, crossover design. In the evening, approximately 20-24 hours after the once daily dose or 12 hours after the twice daily dose, a standardised exercise challenge was performed. Data from 14 patients were available for complete analysis.. The mean (SD) maximal percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0 (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active treatments were not different from each other. The mean (SD) plasma concentrations of montelukast were higher after the twice daily regimen (1.27 (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09) microgram/ml); there was no correlation between the percentage protection against exercise-induced bronchoconstriction and plasma concentrations. After exercise urinary excretion of LTE4 increased significantly during placebo treatment (from 34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of exercise-induced bronchoconstriction.. Montelukast protects similarly against exercise-induced bronchoconstriction between plasma concentrations of 0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after exercise and the protection from exercise-induced bronchoconstriction with a cysteinyl leukotriene receptor antagonist provide further evidence of the role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

Topics: Acetates; Adolescent; Adult; Asthma, Exercise-Induced; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Exercise; Exercise Test; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene E4; Male; Middle Aged; Quinolines; Sulfides

Leptin-related effects on inflammation and bronchial hyperresponsiveness (BHR) in the human airway have not been demonstrated.. To investigate the relationship between the levels of serum leptin and BHR and urinary leukotriene E4 (LTE4) and 9α,11β-prostaglandin F2 (9α,11β-PGF(2)) release after exercise challenge in asthmatic children.. Eighty-six prepubertal children between 6 and 10 years old were enrolled and divided into 4 groups: 19 obese asthmatic children, 25 normal-weight asthmatic children, 21 obese nonasthmatic children, and 21 healthy controls. We measured serum leptin levels and urinary LTE4 and 9α,11β-PGF2 levels in children before and 30 minutes after the exercise challenge.. Serum leptin levels were significantly higher in obese asthmatic children compared with normal-weight asthmatic children. Significant increases in urinary levels of LTE4 and 9α,11β-PGF2 were observed in obese asthmatic children after the exercise challenge. Although smaller than in obese asthmatic children, significant increases in the urinary levels of LTE4 and 9α,11β-PGF2 were also observed in the normal-weight. Asthmatic children Logarithmic serum leptin values were significantly associated with the logarithmic maximum percentage change in forced expiratory volume in 1 second, the logarithmic urinary LTE4 change, and the logarithmic urinary 9α,11β-PGF2 change from baseline to after exercise in both obese and normal-weight asthmatic children.. The serum levels of leptin were significantly associated with BHR and urinary LTE4 and 9α,11β-PGF2 release induced by exercise challenge in asthmatic children.

Topics: Asthma, Exercise-Induced; Child; Dinoprost; Exercise Test; Female; Humans; Leptin; Leukotriene E4; Male; Obesity

Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge.

Topics: Adolescent; Asthma, Exercise-Induced; Biomarkers; Bronchial Provocation Tests; Bronchoconstriction; Chloramines; Chlorine; Dinoprost; Female; Humans; Leukotriene E4; Male; Mannitol; Risk Assessment; Swimming; Uteroglobin; Young Adult

To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma.. 19 cats with experimentally induced asthma and 5 control cats.. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated.. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points.. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

Topics: Animals; Asthma, Exercise-Induced; Bronchoalveolar Lavage Fluid; Cat Diseases; Cats; Cysteine; Enzyme-Linked Immunosorbent Assay; Leukotriene C4; Leukotriene D4; Leukotriene E4; Leukotrienes

To explore the relationship between leukotriene (LT) and exercise-induced asthma.. Twenty-two non-smoking asthmatic patients with a reproducible fall in FEV(1) after exercise by least 10% and 10 normal patients were enrolled. Urinary levels of leukotriene E4 were measured before and 2 hours after exercise. Twelve subjects received cysteinyl LT receptor antagonist Zafirlukast (Ancolate) 20 mg twice a day for three days. Standardized exercise challenge were performed after 72 hours. End points included (1) area under the percent fall in FEV(1) versus time curve (AUC 0-60 min), (2) time to recovery to within 5% of the pre-exercise baseline FEV(1) value, (3) and maximum percent fall in FEV(1) from pre-exercise baseline.. To exercise-induced aothma (EIA) group, urinary LTE4 in 2 hours after exercise were higher than that of in before exercise, P < 0.01. Urinary leukotriene E4 concentration before and 2 hours after exercise were higher than normal subjects. Zafirlukast can caused a significant reduction in AUC(0 - 60 min) (Aera under the FEV(1)-time curve for 0 to 60 minutes after exercise); caused a significant reduction in the maximum percent fall in FEV(1); and Zafirlukast resulted in a shorter time to recovery of FEV(1) to preexercise baseline.. There was an increase in urinary LTE4 during the 2 hours after exercise challenge; Zafirlukast can attenuate EIA. The results indicate that there is an important role of leukotriene in the pathogenesis of exercise-induced asthma.

Topics: Adult; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Female; Humans; Indoles; Leukotriene Antagonists; Leukotriene E4; Leukotrienes; Male; Membrane Proteins; Middle Aged; Phenylcarbamates; Receptors, Leukotriene; Sulfonamides; Tosyl Compounds

To explore the relationship between eosinophils, T lymphocyte, leukotreine (LT) and exercise-induced asthma (EIA).. In 32 asthmatic patients (13 with EIA and 19 asthmatic without EIA) and 8 normal persons, serum eosinophil cationic protein (ECP) and actived T lymphocyte (CD(25)(+)%) in peripheral blood were measured at the time before and 10, 60 minutes after exercise testing. The maximum minute ventilation (V(E)) were also measured. Another 22 non-smoking asthmatic patients with EIA and 10 normal subjects were enrolled for measuring urinary leukotriene E(4) levels before and 2 hours after exercise. EIA patients received zafirlukast 20 mg twice a day for three days. Standardized exercise challenge were performed after 72 hours of medication.. There was a linear relationship between ECP, CD(25)(+)% and the forced expiratory volume in one second (FEV(1)) in asthmatic group (r = -0.79 and -0.61 all P < 0.01). Expressions of IL-4 mRNA, IL-5 mRNA CD(25)(+)% and serum ECP levels showed no significant difference at all testing points between two asthmatic groups, meanwhile, V(E) also showed no difference among three groups. Urinary LTE(4) levels in EIA group increased significantly two hours after exercise. Zafirlukast significantly reduced AUC(0 approximately 60 min) and the percentage of maximum fall in FEV(1) and accelerated the falling FEV(1) to return to pre-exercise baseline.. Hyperventilation during exercise may not be the cause leading to EIA, neither did the activation of T lymphocytes, IL-4 and IL-5 gene expression nor ECP. Leukotriene may play an important role in the pathogenesis of EIA.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Biomarkers; Blood Proteins; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Indoles; Interleukin-4; Interleukin-5; Leukotriene Antagonists; Leukotriene E4; Lung; Lymphocyte Activation; Male; Maximal Voluntary Ventilation; Middle Aged; Peak Expiratory Flow Rate; Phenylcarbamates; Receptors, Interleukin-2; Ribonucleases; Sulfonamides; Th2 Cells; Tosyl Compounds

Exercise-induced asthma is a common phenomenon, the mechanism of which is undetermined. Eosinophils have been suggested as playing a role in its occurrence. We studied the effect of exercise-induced asthma on the cellular and mediator composition of spontaneously obtained sputum. Twenty-five patients with bronchial asthma were investigated by studying sputum spontaneously obtained before and following challenge. One group with (n=9) and one without (n=9) exercise-induced asthma performed exercise challenge. A third group (n=7) performed methacholine challenge. The sputum was analysed using Giemsa staining for differential cell count, measuring eosinophil cationic proteins and mixtures of leukotrienes (D4, E4 and C4) in the liquid phase using ELISA. The group with exercise-induced asthma had a mean drop of 23.7+/-7.4% in FEV1, significantly (P=0.001) higher than the group without it. Following challenges, there were significant increases in sputum eosinophils only in the group with exercise-induced asthma (from 8.1+/-13.9% to 18.3+/-20.2%, P=0.0017) and not in control groups (from 0.9+/-0.9% to 1.5+/-15%) or in those who had methacholine challenge (from 23.6+/-27.2% to 22.3+/-23.8%). Eosinophil cationic proteins did not change significantly in any group. In the liquid phase of the sputum, the amount of leukotrienes increased following exercise in six of the seven patients with exercise-induced asthma in whom it was measured. The influx of eosinophils to the airway in patients who develop exercise-induced asthma can be partially explained by the leukotrienes in the airways of those patients.

Topics: Adolescent; Adult; Analysis of Variance; Asthma, Exercise-Induced; Case-Control Studies; Cell Movement; Enzyme-Linked Immunosorbent Assay; Eosinophils; Exercise Test; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Leukotriene C4; Leukotriene D4; Leukotriene E4; Male; Methacholine Chloride; Sputum; Statistics, Nonparametric

Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced bronchoconstriction by measuring urinary metabolites of mast cell mediators. Twelve nonsmoking subjects with mild asthma and a history of exercise-induced bronchoconstriction exercised on a stationary bicycle ergometer for 5 min at 80% maximum work load. Pulmonary function was monitored and urine was collected before and 30 and 90 min after the provocation. The urinary concentrations of the mast cell markers 9alpha,11beta-prostaglandin (PG)F2 and Ntau-methylhistamine, as well as leukotriene E4 (LTE4) were determined by immunoassay. Seven of the 12 subjects (responders) experienced bronchoconstriction (>15% fall in the forced expiratory volume in one second) following exercise, whereas the pulmonary function of the remaining five subjects (nonresponders) remained stable. The urinary excretion (mean+/-SE) of 9alpha,11beta-PGF2 in the responders increased significantly compared with the nonresponders at 30 (77.1+/-14.4 versus 37.2+/-5.6; p<0.05) and 90 min (79.3+/-8.6 versus 40.4+/-8.5, p<0.05) after exercise challenge. The urinary excretion of Ntau-methylhistamine and LTE4 was not significantly different between the two groups at 30 or 90 min after exercise. The findings represent the first documentation of increased urinary levels of 9alpha,11beta-prostaglandin F2 in adults following exercise challenge and provides clear evidence for mast cell activation during exercise-induced bronchoconstriction in asthmatics.

Topics: Adult; Asthma, Exercise-Induced; Bronchial Provocation Tests; Bronchoconstriction; Dinoprost; Exercise Test; Female; Humans; Immunoenzyme Techniques; Leukotriene E4; Male; Mast Cells; Methylhistamines; Radioimmunoassay; Time Factors

To assess the role of sulfidopeptide leukotrienes in the pathogenesis of exercise-induced asthma (EIA), the urinary levels of leukotriene E4 (LTE4), a metabolite of LTC4 and LTD4, were measured by RIA before and after exercise in 13 children with EIA and 10 healthy children. Mass spectrometry was used to confirm the presence of LTE4 in urine and the specificity of the RIA. There was no significant difference in the urinary LTE4 levels before exercise between the children with asthma and healthy children (109 [21 to 265] versus 122 [45 to 156] pg/mg of creatinine; median and range). Urinary LTE4 levels increased significantly after exercise in the children with EIA (from 109 [21 to 265] to 196 [40 to 655] pg/mg of creatinine; median and range; p less than 0.05) but not in the healthy children. The children with asthma demonstrated no significant correlation between the LTE4 level after exercise and the degree of bronchoconstriction, as revealed by the maximal percent fall in the peak expiratory flow rate. Taken together with a recent study that pretreatment with a potent and selective LTD4 antagonist markedly attenuated EIA, our findings suggest that sulfidopeptide leukotrienes may play some role in the pathogenesis of this type of asthma with other factors also being involved in determining the overall airway response.

Topics: Asthma, Exercise-Induced; Child; Chromatography, High Pressure Liquid; Exercise Test; Humans; Leukotriene E4; Mass Spectrometry; Radioimmunoassay; Regression Analysis; SRS-A; Time Factors

Recent evidence suggests that the cysteinyl-leukotrienes (LTC4, LTD4, and LTE4) may be important in the pathogenesis of exercise-induced asthma. To evaluate the role of these mediators further, nine asthmatic subjects with exercise-induced bronchoconstriction were studied on two occasions. On visit 1, subjects performed 6 min of treadmill exercise; the mean maximal percent fall in FEV1 was 38.0 +/- 5.3%. On visit 2, maximal bronchoconstriction observed after exercise was matched with aerosolized methacholine. Urine was collected in two 90-min fractions (0-90 and 90-180 min) after challenges and analyzed by high-performance liquid chromatography-radioimmunoassay for LTE4. There were no significant differences in urinary LTE4 excretion between exercise and methacholine challenges for the periods 0-90 min (16.9 +/- 5.4 vs. 20.4 +/- 4.2 ng/mmol urinary creatinine), 90-180 min (24.9 +/- 8.2 vs. 20.1 +/- 5.5), or 0-180 min (21.5 +/- 6.5 vs. 18.8 +/- 4.1). Thus in contrast to allergen-induced bronchoconstriction, there is little evidence for enhanced cysteinyl-leukotriene generation in exercise-induced bronchoconstriction as assessed by urinary LTE4. If local release and subsequent participation of functionally active cysteinyl-leukotrienes in the pathways that ultimately lead to bronchoconstriction after exercise challenge do occur, these are of insufficient magnitude to perturb urinary LTE4 excretion.

Topics: Adult; Asthma, Exercise-Induced; Forced Expiratory Volume; Humans; Leukotriene E4; Male; Methacholine Compounds; SRS-A

Urinary levels of leukotriene (LT) E4, a stable end-product of LTC4 and LTD4, were measured before and after exercise in 10 children with severe asthma and seven children with moderate asthma using HPLC and RIA to clarify the relationship of LT to the severity of asthma and to the degree of bronchospasm in exercise-induced asthma. The urinary LTE4 level significantly increased after exercise in the severe asthma group, but not in the moderate asthma group (14.3 +/- 14.5 to 24.3 +/- 20.6 versus 19.6 +/- 12.3 to 17.6 +/- 10.8 ng/mmol creatinine, p less than 0.05). The urinary LTE4 level increased in 10 patients (eight with severe asthma), and it decreased in seven patients (five with moderate asthma). A significant difference in the degree of bronchospasm after exercise (as shown by the maximal % fall in the peak expiratory flow rate), was seen when patients with increased urinary LTE4 excretion were compared with those with decreased excretion (60.4 +/- 17.3 versus 24.1 +/- 14.3%, p less than 0.01). Our findings suggest that exercise-induced asthma, or at least a subtype of exercise-induced asthma, may partly develop through the release of LTC4.

Topics: Asthma, Exercise-Induced; Child; Humans; Hypersensitivity, Immediate; Leukotriene E4; Mast Cells; Peak Expiratory Flow Rate; Physical Exertion; SRS-A

Urinary leukotriene E4 (LTE4) concentrations were measured in six asthmatic subjects after treadmill exercise, and in five asthmatic subjects after allergen challenge. Exercise and allergen challenge produced a 42 +/- 18% (mean +/- SD) and 22 +/- 8% fall in FEV1, respectively. The baseline concentration of urinary LTE4 in subjects challenged with exercise was 64 (27 to 150) pg/mg creatinine (geometric mean and 95% confidence interval), and in those challenged with allergen it was 36 (23 to 59) pg/mg creatinine. Urinary LTE4 concentrations did not change significantly in the 24 h after exercise. In contrast, there was a mean 4-fold increase in urinary LTE4 during the 3 h after allergen challenge.

Topics: Adult; Asthma, Exercise-Induced; Bronchial Provocation Tests; Exercise Test; Female; Humans; Leukotriene E4; Male; SRS-A; Time Factors