dinoprost 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

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

9Alpha,11beta-prostaglandin (PG) F2 is an initial metabolite of PGD2 which has a potent bronchoconstrictive activity.. We measured the urinary levels of 9alpha,11beta-PGF2 in asthmatic children to investigate its role in not only acute asthmatic attack in a time course study but also in exercise-induced asthma (EIA).. In the acute asthma study, 30 asthmatic children were examined. Urine samples were collected on the first, third, and sixth days. Urinary levels of 9alpha,11beta-PGF2 were measured with gas chromatography mass spectrometry using the electron impact method. In the exercise challenge study, 14 children with EIA and 14 children without EIA were studied. Urine samples were collected before exercise challenge, and at 1 h, and 5 h after exercise challenge. Urinary levels of 9alpha,11beta-PGF2 were measured.. Elevated urinary levels of 9alpha,11beta-PGF2, which were observed on the first day when treatment was started in the hospital, were gradually decreased on the third day (P < 0.05), and on the sixth day (P < 0.01). A significant correlation between urinary levels of 9alpha,11beta-PGF2 and symptom scores (P < 0.005) was observed on the first day. In EIA, there was a significant increase in urinary levels of 9alpha,11beta-PGF2 at 1 h (P < 0.01) and at 5 h (P < 0.01) after exercise challenge, but not in the children without EIA.. 9Alpha,11beta-PGF2 may be involved in the pathogenesis of acute and exercise-induced asthma in children.

Topics: Acute Disease; Adolescent; Asthma; Asthma, Exercise-Induced; Child; Child, Preschool; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Time Factors

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