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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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.

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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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.

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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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.

Plasma adrenomedullin levels in children with asthma: Any relation with atopic dermatitis?

Background: Asthma is a chronic, inflammatory disease of the airway, and adrenomedullin (ADM) may have some effects against bronchoconstriction. However, the role(s) of ADM in asthmatic children have not been evaluated yet. The aims of this study were to determine if there are any changes in plasma ADM levels during acute asthma attack, and to search for any association between allergen sensitivity and ADM level in asthmatic children. Methods: Twenty-seven children with acute asthma attack, ranging in age from 5 to 15 years were investigated and compared with 20 controls. Plasma ADM levels (ng/mL) were measured by ELISA method. Results: No significant difference was found in ADM levels between the controls and patients in either the acute attack or remission period. Plasma ADM levels were significantly higher in the acute attack (p = 0.043) compared to the remission period in patients who were considered as having a ‘‘severe attack’’ according to GINA (Global Initiative for Asthma) classification. There were statistically significant correlations between the patients’ AlaTOP and Food Panel 7 levels and plasma ADM levels in the acute attack period (p = 0.010,p = 0.001, respectively). The ADM levels in patients with a history of atopic dermatitis were significantly higher in the acute attack period compared to those without a history of atopic dermatitis (p = 0.007).Conclusion: We speculate that ADM may have a role in children with atopic dermatitis, and may also have a role in the immuno-inflammatory process of asthma(AU)

Plasma adrenomedullin levels in children with asthma: any relation with atopic dermatitis?

BACKGROUND: Asthma is a chronic, inflammatory disease of the airway, and adrenomedullin (ADM) may have some effects against bronchoconstriction. However, the role(s) of ADM in asthmatic children have not been evaluated yet. The aims of this study were to determine if there are any changes in plasma ADM levels during acute asthma attack, and to search for any association between allergen sensitivity and ADM level in asthmatic children. METHODS: Twenty-seven children with acute asthma attack, ranging in age from 5 to 15 years were investigated and compared with 20 controls. Plasma ADM levels (ng/mL) were measured by ELISA method. RESULTS: No significant difference was found in ADM levels between the controls and patients in either the acute attack or remission period. Plasma ADM levels were significantly higher in the acute attack (p=0.043) compared to the remission period in patients who were considered as having a "severe attack" according to GINA (Global Initiative for Asthma) classification. There were statistically significant correlations between the patients' AlaTOP and Food Panel 7 levels and plasma ADM levels in the acute attack period (p=0.010, p=0.001, respectively). The ADM levels in patients with a history of atopic dermatitis were significantly higher in the acute attack period compared to those without a history of atopic dermatitis (p=0.007). CONCLUSION: We speculate that ADM may have a role in children with atopic dermatitis, and may also have a role in the immuno-inflammatory process of asthma.

Prevalence of immediate hypersensitivity reactions to cow's milk in infants based on skin prick test and questionnaire.

OBJECTIVE: Cow's milk (CM) hypersensitivity is one of the most frequent hypersensitivities in infants. The objective of our study was to investigate the prevalence of immediate hypersensitivity to CM based on skin prick test results and to evaluate associated allergic conditions ascertained by questionnaire in infants living in Istanbul. METHODS: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on cow's milk hypersensitivity and other allergic diseases was completed during this interview. A cow's milk skin prick test (SPT) was applied to all infants. An open CM challenge test was then carried out on infants with a positive SPT to CM. RESULTS: Among the 1015 infants who underwent SPT, six (0.59 %) demonstrated immediate hyper-sensitivity to the CM allergen and three (0.29 %) developed a positive response to the CM challenge test. The results of the questionnaire revealed that 112 (11.0 %) of the infants had family history of allergic diseases, 96 infants (9.5 %) had a positive history of recurrent wheezing, and 166 (16.4 %) had a history of skin rash resembling atopic dermatitis. CONCLUSIONS: Our results suggest that CM hyper-sensitivity, with its low prevalence, might not be a serious health concern in Turkish infants.

Prevalence of egg sensitization in Turkish infants based on skin prick test.

AIM: Egg allergy is one of the most frequent allergies in infants. The aim of this study was to determine the frequency of sensitization to egg in infants based on skin prick test results and to evaluate associated allergic conditions by questionnaire. METHODS: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on food allergy and other allergic diseases was completed during this interview. An egg skin prick test (whole egg) was applied to all infants. RESULTS: Positive skin prick test results were recorded in 19 infants (1.87 %). There was no difference between the prick test-positive and -negative groups with respect to any of the demographic characteristics investigated (gender, age, birth weight, egg consumption, age of introduction of egg and other solids, breastfeeding). No significant association was demonstrated between sensitization to egg and family history of allergy. Moreover, there was no association between sensitization to egg and occurrence of atopic dermatitis, recurrent wheezing, gastrointestinal symptoms and doctor diagnosis of asthma. CONCLUSION: The prevalence of egg sensitization based on skin prick test results has been found as 1.87 % among Turkish infants in Istanbul. However, no significant relationship was found between allergic sensitization to egg and occurrence of allergic diseases in this study population.

Prevalence of immediate hypersensitivity reactions to cow’s milk in infants based on skin prick test and questionnaire

Objective: Cow’s milk (CM) hypersensitivity is one of the most frequent hypersensitivities in infants.The objective of our study was to investigate the prevalence of immediate hypersensitivity to CM based on skin prick test results and to evaluate associated allergic conditions ascertained by questionnaire in infants living in Istanbul. Methods: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnairere questing data on cow’s milk hypersensitivity and other allergic diseases was completed during this interview. A cow’s milk skin prick test (SPT) was applied to all infants. An open CM challenge test was then carried out on infants with a positive SPT to CM. Results: Among the 1015 infants who underwent SPT, six (0.59%) demonstrated immediate hypersensitivity to the CM allergen and three (0.29 %) developed a positive response to the CM challenge test. The results of the questionnaire revealed that 112 (11.0 %) of the infants had family history of allergic diseases, 96 infants (9.5 %) had a positive history of recurrent wheezing, and 166 (16.4 %) had a history of skin rash resembling atopic dermatitis. Conclusions: Our results suggest that CM hypersensitivity, with its low prevalence, might not be a serious health concern in Turkish infants

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Serum leptin level in acute myeloid leukemia patients.

Leptin is a regulator of fat metabolism that is synthesized in adipocytes and released into circulation. The serum levels of leptin are, therefore, correlated with body fat mass and show a wide variation in healthy individuals. Leptin may have an additional indirect effect on leukemic hematopoesis. We investigated serum leptin levels with enzyme-linked immunosorbent assays in 14 acute myeloblastic leukemia (AML) patients before and after chemotherapy and compared the results with that of the levels determined 14 healthy controls. We found no significant difference between leptin levels before and after chemotherapy and control group. Therefore, serum leptin level should not be used as a diagnostic marker in acute leukemia patients. However, the possibility of regional leptin production by leukemia blasts in bone marrow stroma creates a high local concentration of leptin within bone marrow microenvironment and systemic leptin level in combination with local leptin production may affect leukemic hematopoesis.

Prevalence of egg sensitization in Turkish infants based on skin prick test

Aim: Egg allergy is one of the most frequent allergies in infants. The aim of this study was to determine the frequency of sensitization to egg in infants based on skin prick test results and to evaluate associated allergic conditions by questionnaire. Methods: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on food allergy and other allergic diseases was completed during this interview. An egg skin prick test (whole egg) was applied to all infants. Results: Positive skin prick test results were recorded in 19 infants (1.87 %). There was no difference between the prick test-positive and -negative groups with respect to any of the demographic characteristics investigated (gender, age, birth weight, egg consumption, age of introduction of egg and other solids, breastfeeding). No significant association was demonstrated between sensitization to egg and family history of allergy. Moreover, there was no association between sensitization to egg and occurrence of atopic dermatitis, recurrent wheezing, gastrointestinal symptoms and doctor diagnosis of asthma. Conclusion: The prevalence of egg sensitization based on skin prick test results has been found as 1.87 % among Turkish infants in Istanbul. However, no significant relationship was found between allergic sensitization to egg and occurrence of allergic diseases in this study population

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Frequency of allergic diseases following measles.

OBJECTIVE: Viral and bacterial infections in childhood decrease the likelihood of allergic diseases in later life. The frequency of allergic diseases in patients with a history of measles has been reported to be low but some studies still suggest that measles can increase the frequency of allergic diseases. The aim of this study was to investigate the frequency of allergic diseases following measles in childhood. METHODS: Fifty-two children hospitalized in our clinic with measles were compared with 51 children without measles. Allergic diseases were investigated in both groups by using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. In all children, allergy skin tests were performed with the four most common allergens. RESULTS: Sensitivity to Dermatophagoides pteronyssinus was less frequent in children with measles than in those without (p < 0.05). A history of nebulized salbutamol use in the emergency room in the previous 12 months was also less frequent in the measles group (p < 0.05). Inhaled corticosteroid use was more common in the group without measles (p < 0.05). CONCLUSION: The results of this study indicate that findings of allergic disease are less frequent in children with a history of measles. These children were less sensitive to D. pteronyssinus.

Frequency of allergic diseases following measles / Frecuencia de enfermedades alergicas después del sarampión

Objective: Viral and bacterial infections in childhood decrease the likelihood of allergic diseases in later life. The frequency of allergic diseases in patients with a history of measles has been reported to be low but some studies still suggest that measles can increase the frequency of allergic diseases. The aim of this study was to investigate the frequency of allergic diseases following measles in childhood. Methods: Fifty-two children hospitalized in our clinic with measles were compared with 51 children without measles. Allergic diseases were investigated in both groups by using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. In all children, allergy skin tests were performed with the four most common allergens. Results: Sensitivity to Dermatophagoides pteronyssinus was less frequent in children with measles than in those without (p < 0.05). A history of nebulized salbutamol use in the emergency room in the previous 12 months was also less frequent in the measles group (p < 0.05). Inhaled corticosteroid use was more common in the group without measles (p < 0.05). Conclusion: The results of this study indicate that findings of allergic disease are less frequent in children with a history of measles. These children were less sensitive to D. pteronyssinus

Objetivo: Las infecciones virales y bacterianas durante la niñez disminuyen la probabilidad de enfermedades alérgicas en los años posteriores. Sin embargo, a pesar de los trabajos sobre la baja frecuencia de enfermedad alérgica en pacientes con historia de sarampión, algunos estudios todavía sugieren que esta enfermedad puede causer un incremento de la frecuencia de patología alérgica. El propósito de este estudio fue investigar la frecuencia de enfermedades alérgica acaecidas después del sarampión. Métodos: Cincuenta y dos niños con sarampión hospitalizados en nuestra clínica, fueron comparados con otros 51 que no padecían la enfermedad. En ambos grupos se investigó la enfermedad alérgica por medio del cuestionario ISAAC. A todos los niños se les practicaron pruebas cutáneas a los cuatro alergenos más comunes. Resultados: La sensibilidad a D. pteronyssinus fue menos frecuente en niños con sarampión (p<0.05). La administración de salbutamol nebulizado en el servicio de urgencias en los 12 meses anteriores fue también menos frecuente en el grupo con sarampión (p<0.05). El uso de corticoides inhalados fue más común en el grupo sin sarampión (p<0.05). Conclusiones: Los resultados de este estudio indican que la incidencia de enfermedades alérgicas es menos frecuente en niños con historia de sarampión. En un menor porcentaje de estos niños se demostró sensibilización al D. pteronyssinus