8-epi-prostaglandin-f2alpha and Hypersensitivity

Leukotriene (LT) E(4) and 8-isoprostane concentrations are elevated in exhaled breath condensate in children with asthma. The effects of leukotriene receptor antagonists (LTRAs) on exhaled leukotriene and prostanoids in children with asthma are unknown.. (1) To study the effect of montelukast, a LTRA, on exhaled LTE(4), 8-isoprostane, and prostaglandin E(2) in children with asthma and atopic children; (2) to measure exhaled nitric oxide.. An open-label study with oral montelukast (5 mg once daily for 4 weeks) was undertaken in 17 atopic children with asthma and 16 atopic children without asthma.. Pretreatment exhaled LTE(4) (P < .0001) and 8-isoprostane (P < .0001) values were higher in atopic children with asthma than in atopic children without asthma. In atopic children with asthma, montelukast reduced exhaled LTE(4) by 33% (P < .001), and this reduction was correlated with pretreatment LTE(4) values (r = -0.90; P = .0001). Posttreatment exhaled LTE(4) levels in children with asthma were higher than pretreatment LTE(4) values in atopic children without asthma (P < .004). Montelukast had no effect on exhaled LTE(4) in atopic children without asthma (P = .74), or on exhaled 8-isoprostane (atopic children with asthma, P = .94; atopic children without asthma, P = .55) and PGE(2) (atopic children with asthma, P = .56; atopic children without asthma, P = .93) in both groups. In atopic children with asthma, exhaled nitric oxide concentrations were reduced by 27% (P < .05) after montelukast.. Leukotriene receptor antagonists decrease exhaled LTE(4) in atopic children with asthma. This reduction is dependent on baseline exhaled LTE(4) values.. Measurement of exhaled LTE(4) might help identify children with asthma most likely to benefit from LTRAs.

Topics: Acetates; Allergens; Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Child; Cross-Sectional Studies; Cyclopropanes; Dinoprost; Dinoprostone; Humans; Hypersensitivity; Leukotriene Antagonists; Leukotriene E4; Nitric Oxide; Quinolines; Skin Tests; Spirometry; Sulfides

Enhanced oxidative stress has been described in adults who suffer from symptoms of asthma and poor lung function. This study assessed the relation between markers of oxidative stress and antioxidant status and lung function, symptoms of asthma, atopy and bronchial hyperresponsiveness (BHR) in young adults.. A sub-sample of 589 individuals aged 22-28 years, selected from a total of 1232 included in a survey assessing early and current risk factors for chronic diseases, participated in the study. Participants were from an agricultural area of Chile, responded to a Spanish version of the European Community Respiratory Health Survey questionnaire, were skin tested to eight allergens, and challenged with methacholine to assess BHR. Five hundred and eighty-five individuals had measures of plasma biomarkers ferric reducing ability of plasma, uric acid, protein carbonyls and 564 had 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) assessed.. All participants had detectable plasma 8-iso-PGF(2alpha) and carbonyl levels. There was no indication for an association between markers of antioxidant status or oxidative stress with any of the outcomes studied.. The levels of oxidative stress-related biomarkers and antioxidant status in plasma may not be related to asthma in the general population in the absence of more severe symptoms or exacerbations.

Topics: Adult; Allergens; Antioxidants; Asthma; Biomarkers; Blood Proteins; Body Mass Index; Dinoprost; Female; Ferric Compounds; Forced Expiratory Volume; Humans; Hypersensitivity; Male; Oxidation-Reduction; Oxidative Stress; Protein Carbonylation; Respiratory Function Tests; Respiratory Sounds; Uric Acid; Vital Capacity; Young Adult

We investigated the role of antioxidants in airway hyperresponsiveness to acetylcholine using young asthma model mice, which were sensitized and stimulated with ovalbumin.. The mice had been fed either a normal diet, an alpha-tocopherol-supplemented diet or a probucol-supplemented diet 14 days before the first sensitization. They were immunized with antigen at intervals of 12 days and, starting from 10 days after the second immunization, they were exposed to antigen 3 times every 4th day using an ultrasonic nebulizer. Twenty-four hours after the last antigen inhalation, airway responsiveness to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was collected. A blood and lung tissue study was also carried out.. Twenty-four hours after the last antigen challenge, both IL-4 and IL-5 in the BALF of alpha-tocopherol-supplemented mice were significantly decreased. The IL-5 level in probucol-supplemented mice was also decreased, but there was no difference in IL-4 levels. The serum IgE level was decreased in probucol-supplemented mice. Differential cell rates of the fluid revealed a significant decrease in eosinophils due to antioxidant supplementation. Airway hyperresponsiveness to acetylcholine was also repressed in antioxidant-supplemented mice. In histological sections of lung tissue, inflammatory cells and mucus secretion were markedly reduced in antioxidant-supplemented mice. We investigated the antioxidant effect on our model mice by examining 8-isoprostane in BALF and lung tissue, and acrolein in BALF; however, our experiment gave us no evidence of the antioxidant properties of either alpha-tocopherol or probucol contributing to the reduction of airway inflammation.. These findings indicate that alpha-tocopherol and probucol suppress allergic responses in asthma model mice, although these two drugs cause suppression in different ways that are unrelated to antioxidation.

Topics: Acrolein; Allergens; alpha-Tocopherol; Animals; Antioxidants; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Dietary Supplements; Dinoprost; Disease Models, Animal; Eosinophils; Female; Hypersensitivity; Immunoglobulin E; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Probucol