Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a chronic asthma model

BACKGROUND: Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. METHODS: A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. RESULTS: The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. CONCLUSIONS: The results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis

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The efficacy of single-high dose inhaled corticosteroid versus oral prednisone treatment on exhaled leukotriene and 8-isoprostane levels in mild to moderate asthmatic children with asthma exacerbation

BACKGROUND: The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation. METHODS: Ninety-four children with moderate-severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 μg) or P and after six days of treatment with FP-1000 μg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS: Both single high-dose FP (n = 59) and p (n = 35) treatment resulted in a significant improvement in asthma score (p < 0.0001), PEF (p < 0.0001), and FEV1 (p < 0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p = 0.001), and at the end of the six-day period in the FP group (p < 0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 μg/day in the FP group (p = 0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p = 0.012) and six days of P treatment (p = 0.018) in children with asthma exacerbation. CONCLUSIONS: High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later

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Relationship between exhaled leukotriene and 8-isoprostane levels and asthma severity, asthma control level, and asthma control test score

OBJECTIVE: Exhaled breath condensate (EBC) is a completely non-invasive method for the collection of airway secretions to measure intense inflammation in the airways of asthmatics. It has been shown that the childhood asthma control test (c-ACT) is a good tool for use in the evaluation of asthmatics. Whether the c-ACT score and asthma control level correlate with the airway inflammation is not well known. We aimed to evaluate the relationship between exhaled cysteinyl leukotrienes (Cys-LTs) and 8-isoprostane levels and asthma severity, asthma control level and c-ACT score in asthmatic children. METHODS: Thirty asthmatic children were evaluated with c-ACT score and pulmonary function tests. Asthma severity and asthma control level were assessed according to GINA. EBC was collected and Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS: Exhaled 8-isoprostane level in patients with moderate persistent asthma [114 (55-146) pg/ml] was higher than in the mild persistent group [52 (21-91) pg/ml] (p = 0.05, Mann-Whitney U [MWU]). EBC 8-isoprostane in children with 1-4 asthma exacerbations/year [52 (16-80) pg/ml] was significantly lower than in children with > 4 asthma exacerbations/year [114 (57-129) pg/ml] (p < 0.05, MWU). No significant relation was determined between exhaled 8-isoprostane and Cys-LTs levels and c-ACT score and asthma control level. Exhaled 8-isoprostane correlated negatively with bronchodilator response (p = 0.015, r = −0.45). CONCLUSIONS: Exhaled 8-isoprostane, as an oxidative stress specifier, was found to be increased in relation with asthma exacerbation frequency and oxidative stress increases with the severity of asthma. In contrast to asthma severity level, c-ACT score and asthma control level may not reflect airway inflammation

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