Atopy patch test in children with cow's milk and hen's egg allergy: Do clinical symptoms matter?

INTRODUCTION AND OBJECTIVES: Since early 2000s, atopy patch test (APT) has been used to determine non-IgE and mixed-type food allergies. Previous studies have reported conflicting results about the diagnostic value of APT in food allergies, due to non-standardized methods. We aimed to determine the diagnostic efficacy of APT compared to open oral food challenge (OFC) in patients diagnosed with cow's milk allergy (CMA) and hen's egg allergy (HEA) manifesting as atopic dermatitis (AD) and gastrointestinal system symptoms. MATERIALS AND METHODS: In patients with suspected AD and/or gastrointestinal manifestations due to CMA and HEA, the results of OFC, APT, skin prick test (SPT) and specific IgE (sIgE) were reviewed. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of sIgE, SPT, APT and SPT+APT were calculated. RESULTS: In total 133 patients with suspected CMA (80) and HEA (53) were included in the study. In patients with CMA presenting with gastrointestinal symptoms, APT had sensitivity of 9.1%, specificity of 100%, PPV of 100% and NPV of 48.7%. In atopic dermatitis patients, sensitivity of APT was 71.4%, specificity 90.6%, PPV 62.5% and NPV 93.6%. In patients diagnosed with HEA, the sensitivity, specificity, PPV and NPV values of APT were 72.0%, 78.6%, 47.2% and 75.0%, respectively. In patients diagnosed with HEA presenting with AD, sensitivity of APT was 87.5%, specificity 70.6%, PPV 73.7% and NPV 85.7%. Atopy patch test had lower sensitivity (44.4%) and higher specificity (90.9%) in patients diagnosed with HEA presenting with gastrointestinal symptoms than those presenting with AD. CONCLUSION: Our study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms

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Atopy patch test in children with cow's milk and hen's egg allergy: Do clinical symptoms matter?

INTRODUCTION AND OBJECTIVES: Since early 2000s, atopy patch test (APT) has been used to determine non-IgE and mixed-type food allergies. Previous studies have reported conflicting results about the diagnostic value of APT in food allergies, due to non-standardized methods. We aimed to determine the diagnostic efficacy of APT compared to open oral food challenge (OFC) in patients diagnosed with cow's milk allergy (CMA) and hen's egg allergy (HEA) manifesting as atopic dermatitis (AD) and gastrointestinal system symptoms. MATERIALS AND METHODS: In patients with suspected AD and/or gastrointestinal manifestations due to CMA and HEA, the results of OFC, APT, skin prick test (SPT) and specific IgE (sIgE) were reviewed. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of sIgE, SPT, APT and SPT+APT were calculated. RESULTS: In total 133 patients with suspected CMA (80) and HEA (53) were included in the study. In patients with CMA presenting with gastrointestinal symptoms, APT had sensitivity of 9.1%, specificity of 100%, PPV of 100% and NPV of 48.7%. In atopic dermatitis patients, sensitivity of APT was 71.4%, specificity 90.6%, PPV 62.5% and NPV 93.6%. In patients diagnosed with HEA, the sensitivity, specificity, PPV and NPV values of APT were 72.0%, 78.6%, 47.2% and 75.0%, respectively. In patients diagnosed with HEA presenting with AD, sensitivity of APT was 87.5%, specificity 70.6%, PPV 73.7% and NPV 85.7%. Atopy patch test had lower sensitivity (44.4%) and higher specificity (90.9%) in patients diagnosed with HEA presenting with gastrointestinal symptoms than those presenting with AD. CONCLUSION: Our study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms.

The efficiency of the symptom-based score in infants diagnosed with cow's milk protein and hen's egg allergy

Introduction and objectives: Symptom-based score (SBS) quantifies the number and severity of suspected cow's milk-related symptoms. In this study, we aimed to evaluate the efficiency of SBS in patients diagnosed with cow's milk protein (CMPA) and hen's egg allergy (HEA). Materials and methods: A single-center study was conducted between June 2015 and August 2017. Infants who were diagnosed with CMPA and HEA or both were enrolled in the study. SBS was applied at baseline and at one month during an elimination diet. Results: One hundred and twelve patients were enrolled in the study. Of these, 56 (50%) were female. Forty-nine (43.8%) patients were diagnosed with CMPA, 39 (34.8%) patients were diagnosed with HEA and 24 (21.4%) patients were diagnosed with cow's milk protein and hen's egg allergy (CMPHEA). In the analysis of SBS, median Bristol scale and initial total symptom-based scores were significantly lower in the HEA group than others (p = 0.002; p = 0.025). After the elimination diet, mean SBS decrease in the CMPHEA group (11.3 ± 4.7) was found to be higher than CMPA (8.8 ± 3.7) and HEA (8.0 ± 4.0) groups (p = 0.009). In 41 (83.7%) patients with CMPA, 33 (84.6%) patients with HEA and 21 (87.5%) patients with CMPHEA, a ≥ 50% decrease in SBS was observed after the elimination diet. Conclusion: We may conclude that the present study suggests that SBS can be useful in monitoring the response to elimination diet in infants diagnosed with cow's milk protein and hen's egg allergy

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The efficiency of the symptom-based score in infants diagnosed with cow's milk protein and hen's egg allergy.

INTRODUCTION AND OBJECTIVES: Symptom-based score (SBS) quantifies the number and severity of suspected cow's milk-related symptoms. In this study, we aimed to evaluate the efficiency of SBS in patients diagnosed with cow's milk protein (CMPA) and hen's egg allergy (HEA). MATERIALS AND METHODS: A single-center study was conducted between June 2015 and August 2017. Infants who were diagnosed with CMPA and HEA or both were enrolled in the study. SBS was applied at baseline and at one month during an elimination diet. RESULTS: One hundred and twelve patients were enrolled in the study. Of these, 56 (50%) were female. Forty-nine (43.8%) patients were diagnosed with CMPA, 39 (34.8%) patients were diagnosed with HEA and 24 (21.4%) patients were diagnosed with cow's milk protein and hen's egg allergy (CMPHEA). In the analysis of SBS, median Bristol scale and initial total symptom-based scores were significantly lower in the HEA group than others (p=0.002; p=0.025). After the elimination diet, mean SBS decrease in the CMPHEA group (11.3±4.7) was found to be higher than CMPA (8.8±3.7) and HEA (8.0±4.0) groups (p=0.009). In 41 (83.7%) patients with CMPA, 33 (84.6%) patients with HEA and 21 (87.5%) patients with CMPHEA, a ≥50% decrease in SBS was observed after the elimination diet. CONCLUSION: We may conclude that the present study suggests that SBS can be useful in monitoring the response to elimination diet in infants diagnosed with cow's milk protein and hen's egg allergy.

Sinomenine ameliorates the airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in a murine model of chronic asthma

Background: Sinomenine (SIN), an alkaloid isolated from the root of Sinomenium acutum which has a variety of pharmacological effects, including anti-inflammation, immunosuppression and anti-angiogenesis. The present study aimed to evaluate the effects of SIN on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. Methods: Twenty-two BALB/c mice were divided into four groups; I (control), II (placebo), III, IV. Mice in groups III and IV received the SIN (100 mg/kg), and dexamethasone (1 mg/kg) respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide in bronchoalveolar lavage fluid (BALF) and ovalbumin-specific immunoglobulin (Ig) E in serum were quantified by standard ELISA protocols. Results: The dose of 100 mg/kg SIN treatment provided beneficial effects on all of the histopathological findings of airway remodelling compared to placebo (p < 0.05). All cytokine levels in BALF and serum and immunohistochemical scores were significantly lower in 100 mg/kg SIN treated group compared to the placebo (p < 0.05). Conclusions: These findings suggested that the dose of 100 mg/kg SIN improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells (AU)

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Sinomenine ameliorates the airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in a murine model of chronic asthma.

BACKGROUND: Sinomenine (SIN), an alkaloid isolated from the root of Sinomenium acutum which has a variety of pharmacological effects, including anti-inflammation, immunosuppression and anti-angiogenesis. The present study aimed to evaluate the effects of SIN on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. METHODS: Twenty-two BALB/c mice were divided into four groups; I (control), II (placebo), III, IV. Mice in groups III and IV received the SIN (100mg/kg), and dexamethasone (1mg/kg) respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-ß), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide in bronchoalveolar lavage fluid (BALF) and ovalbumin-specific immunoglobulin (Ig) E in serum were quantified by standard ELISA protocols. RESULTS: The dose of 100mg/kg SIN treatment provided beneficial effects on all of the histopathological findings of airway remodelling compared to placebo (p<0.05). All cytokine levels in BALF and serum and immunohistochemical scores were significantly lower in 100mg/kg SIN treated group compared to the placebo (p<0.05). CONCLUSIONS: These findings suggested that the dose of 100mg/kg SIN improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.

Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma

Background and aims: In previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. Methods: Twenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50mg/kg UDCA, OVA-150 mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50 mg/kg UDCA, OVA-150 mg/kg UDCA, OVA-Dexamethasone received the UDCA (50 mg/kg), UDCA (150 mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified. Results: The dose of 150 mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo. Conclusions: These findings suggested that the dose of 150 mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells (AU)

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Knowledge, perspectives and attitudes about allergen-specific immunotherapy for respiratory allergic disease among paediatricians in Turkey

BACKGROUND: Allergen-specific immunotherapy (ASI) is the only effective treatment for allergic respiratory diseases which has the potential to change the natural course of the disease. In this present study we aimed to evaluate the paediatricians' knowledge, perspectives and attitudes about ASI for allergic respiratory diseases. MATERIALS AND METHODS: The study was conducted between September 2014 - January 2015. A survey of 25 questions assessing paediatricians' knowledge, perceptions and attitudes about ASI was developed by an expert panel and applied by physicians in hospitals in Izmir, Turkey, where the paediatricians work. Data were recorded in SPSS for Windows V.16. Descriptive statistics, chi square analysis was used. P<0.05 was considered as significant. RESULTS: Fully completed surveys from 180 paediatricians were analysed. The respondent paediatricians had an age of 37±8.2 years, and 56 of them were male. The majority of the respondents (n: 146) were working fewer than five years as a paediatric specialist. 93.9% of the paediatricians believed that ASI was effective for the treatment of allergic respiratory diseases. There was satisfactory knowledge of the characteristics, aims, effects and limits of ASI. CONCLUSION: ASI is generally well-known and accepted among paediatricians. A better synergy between paediatricians and paediatric allergy specialists can provide more use of this treatment method for allergic respiratory diseases in childhood

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Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma.

BACKGROUND AND AIMS: In previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. METHODS: Twenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone received the UDCA (50mg/kg), UDCA (150mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-ß), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified. RESULTS: The dose of 150mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo. CONCLUSIONS: These findings suggested that the dose of 150mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.

Efficacy of parthenolide on lung histopathology in a murine model of asthma

BACKGROUND: Parthenolide is the active constituent of the plant 'Tanacetum parthenium' (Feverfew) which has been used for centuries as a folk remedy for inflammatory conditions. Aim of the study: In this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma. MATERIALS AND METHODS: Thirty-five BALB/c mice were divided into five groups; I (control), II (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and parthenolide combination). Lung histology was evaluated after treatment with the study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA. RESULTS: Histologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo. All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group. Improvement of most of the histologic parameters was similar in Groups III and V. Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group. CONCLUSION: We demonstrated that parthenolide administration alleviated some of the pathological changes in asthma. But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment

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Knowledge, perspectives and attitudes about allergen-specific immunotherapy for respiratory allergic disease among paediatricians in Turkey.

BACKGROUND: Allergen-specific immunotherapy (ASI) is the only effective treatment for allergic respiratory diseases which has the potential to change the natural course of the disease. In this present study we aimed to evaluate the paediatricians' knowledge, perspectives and attitudes about ASI for allergic respiratory diseases. MATERIALS AND METHODS: The study was conducted between September 2014 - January 2015. A survey of 25 questions assessing paediatricians' knowledge, perceptions and attitudes about ASI was developed by an expert panel and applied by physicians in hospitals in Izmir, Turkey, where the paediatricians work. Data were recorded in SPSS for Windows v.16. Descriptive statistics, chi square analysis was used. P<0.05 was considered as significant. RESULTS: Fully completed surveys from 180 paediatricians were analysed. The respondent paediatricians had an age of 37±8.2 years, and 56 of them were male. The majority of the respondents (n: 146) were working fewer than five years as a paediatric specialist. 93.9% of the paediatricians believed that ASI was effective for the treatment of allergic respiratory diseases. There was satisfactory knowledge of the characteristics, aims, effects and limits of ASI. CONCLUSION: ASI is generally well-known and accepted among paediatricians. A better synergy between paediatricians and paediatric allergy specialists can provide more use of this treatment method for allergic respiratory diseases in childhood.

Efficacy of parthenolide on lung histopathology in a murine model of asthma.

BACKGROUND: Parthenolide is the active constituent of the plant 'Tanacetum parthenium' (Feverfew) which has been used for centuries as a folk remedy for inflammatory conditions. AIM OF THE STUDY: In this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma. MATERIALS AND METHODS: Thirty-five BALB/c mice were divided into five groups; I (control), II (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and parthenolide combination). Lung histology was evaluated after treatment with the study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA. RESULTS: Histologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo. All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group. Improvement of most of the histologic parameters was similar in Groups III and V. Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group. CONCLUSION: We demonstrated that parthenolide administration alleviated some of the pathological changes in asthma. But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment.

Cerebrovascular reactivity and neurovascular coupling in patients with obstructive sleep apnea.

AIM: Obstructive sleep apnea syndrome (OSAS) has been implicated as an independent risk factor for stroke. There are data suggesting the presence of lower cerebrovascular reactivity (CVR) as determined by transcranial Doppler (TCD) in patients with OSAS. We concurrently investigated neurovascular coupling (NVC) with visual stimulation, and CVR using breath-holding (BH) test on TCD in patients with OSAS. MATERIALS AND METHODS: Data were collected in 49 patients with moderate to severe OSAS, and compared to 15 healthy subjects matched for age and risk factors. The CVR to hypercapnia was measured by BH test, and the NVC was performed with visual stimulation. RESULTS: There were no significant differences in baseline characteristics of patients and controls, except for BMI, which was significantly higher in patients with OSAS (p = 0.036). OSAS patients showed significantly lower reactivity during BH in comparison to controls (36.9% ± 14.0% vs. 46.6% ± 20.1%; p = 0.019). The reactivity time was also significantly shorter in the OSAS group (8.0 ± 4.2 s) when compared to controls (10.1 ± 4.3 s; p = 0.015). The visual stimulation produced similar reactivity in patients (27.7% ± 9.4%) and controls (29.1 ± 13.9; p > 0.05). CONCLUSIONS: Our data demonstrate a diminished vasodilator response capacity only to a strong stimulator such as hypercapnia in OSAS patients. However, the NVC, as shown by the TCD, is quite normal, suggesting that a weak or mild stimulation produces a proper reactivity among OSAS patients.

Allergic reactions to Hymenoptera stings in Turkish school children

BACKGROUND: Reported prevalence of the insect stings and rates of allergic reactions vary among studies. The aim of the present study was to carry out the first epidemiological study on the prevalence of Hymenoptera allergy among school children in Izmir, Turkey. METHODS: We planned to reach 6100 children, assuming the frequency of allergic reactions to Hymenoptera stings as 20%. Thirty-seven and eight schools were chosen from rural and urban areas, respectively. Parents were asked to complete a questionnaire which included questions about history of insect stings and the presence of atopic disease. All cases with severe systemic reactions and a representative sample from the remaining population were surveyed by telephone afterwards. RESULTS: A total of 8565 questionnaires were distributed and the response rate was 70.8%. Of the 5602 children, 61.6% were stung at least once in their lifetime. Of these, 24.3% had a LLR, 8.1% had a MSR, 0.8% had a SSR. Overall reliability of the questionnaire was calculated as 40.7% for SSR and 91.6% for other reactions after telephone survey. On logistic regression analysis, male sex and rural residence were associated with a higher risk of being stung (OR: 1.39; CI 1.25-1.56; OR: 4.37; CI 3.36-5.69, respectively). Male subjects and asthmatic children were more likely to experience a SSR (OR: 2.44; CI 1.06-5.65; OR: 3.3; CI 1.52-7.19, respectively). CONCLUSION: Hymenoptera stings are common in our population and large local reactions are the most common type of reactions. Prevalence of severe reactions is low in our population compared to previous studies

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Allergic reactions to Hymenoptera stings in Turkish school children.

BACKGROUND: Reported prevalence of the insect stings and rates of allergic reactions vary among studies. The aim of the present study was to carry out the first epidemiological study on the prevalence of Hymenoptera allergy among school children in Izmir, Turkey. METHODS: We planned to reach 6100 children, assuming the frequency of allergic reactions to Hymenoptera stings as 20%. Thirty-seven and eight schools were chosen from rural and urban areas, respectively. Parents were asked to complete a questionnaire which included questions about history of insect stings and the presence of atopic disease. All cases with severe systemic reactions and a representative sample from the remaining population were surveyed by telephone afterwards. RESULTS: A total of 8565 questionnaires were distributed and the response rate was 70.8%. Of the 5602 children, 61.6% were stung at least once in their lifetime. Of these, 24.3% had a LLR, 8.1% had a MSR, 0.8% had a SSR. Overall reliability of the questionnaire was calculated as 40.7% for SSR and 91.6% for other reactions after telephone survey. On logistic regression analysis, male sex and rural residence were associated with a higher risk of being stung (OR: 1.39; CI 1.25-1.56; OR: 4.37; CI 3.36-5.69, respectively). Male subjects and asthmatic children were more likely to experience a SSR (OR: 2.44; CI 1.06-5.65; OR: 3.3; CI 1.52-7.19, respectively). CONCLUSION: Hymenoptera stings are common in our population and large local reactions are the most common type of reactions. Prevalence of severe reactions is low in our population compared to previous studies.

Sequencing of the CFTR gene in selected Turkish patients with cystic fibrosis.

AIM: Common mutation detection panels are usually used in clinical practice in most of the centers of our country in order to demonstrate mutations of cystic fibrosis (CF) patients. But heterogenicity of CFTR mutations in Turkey makes identification of CFTR mutations extremely difficult while using common mutation detection panels. METHODS: In this report, we described our experience and findings in offering sequencing of the CFTR gene to 17 patients in which no mutations were identified by common mutation analysis. RESULTS: Overall allele informativity increased from 4/34 (11.76%) to 13/34 (38.2%) after whole exon sequencing of CFTR in our patients. CONCLUSION: Genotype of CF patients could be entirely described in some of our patients by CFTR sequencing but there is still a group of patients, independently from their clinical classification whose mutations can not be determined by CFTR sequencing.

Beneficial effects of arginase inhibition and inhaled l -arginine administration on airway histology in a murine model of chronic asthma

BACKGROUND: Increased arginase activity in the airways induces reduced bioavailability of l -arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled l -arginine and arginase inhibitor Nω-hydroxy-nor- l -arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue. METHODS: Forty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled l -arginine, nor-NOHA, l -arginine-nor-NOHA combination, budesonide and placebo. Interleukin (IL)-4 and IL-5 levels are determined in lung homogenates with ELISA. RESULTS: l -Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA. CONCLUSION: We demonstrated that inhaled l -arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment

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Beneficial effects of arginase inhibition and inhaled L-arginine administration on airway histology in a murine model of chronic asthma.

BACKGROUND: Increased arginase activity in the airways induces reduced bioavailability of L-arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled L-arginine and arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue. METHODS: Forty-two BALB/c mice were divided into six groups: I (control), II (placebo), III, IV, V and VI. All mice except for control group were sensitised by an intraperitoneal injection of ovalbumin with alum adjuvant and then challenged with an aerosol of ovalbumin on three days of the week for eight weeks beginning from the 21st day of the study. Lung histology and bronchoalveolar lavage cell (BAL) counts were evaluated after treatment with inhaled L-arginine, nor-NOHA, l-arginine-nor-NOHA combination, budesonide and placebo. Interleukin(IL)-4 and IL-5 levels are determined in lung homogenates with ELISA. RESULTS: L-Arginine group was similar to budesonide group in lowering all histological parameters. Results of groups treated with nor-NOHA were also similar to budesonide group except for epithelial thickness. The number of eosinophils in BAL decreased significantly in groups receiving study drugs. Decrease was only noted in IL-4 levels in group receiving nor-NOHA. CONCLUSION: We demonstrated that inhaled l-arginine administration alleviated all histological parameters similar to budesonide and treatment with arginase inhibitor improved not all but some of the pathological changes in chronic asthma. Combination therapy had no additive effect on either treatment.

Plasminogen activator inhibitor-1 and angiotensin converting enzyme gene polymorphisms in Turkish asthmatic children

Background: Polymorphisms of plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes have been implicated in susceptibility to asthma. In this study, we aimed to investigate whether there was any association between childhood asthma and polymorphisms of the PAI-1 and ACE genes. Methods: Two hundred and three Turkish children aged 5–15 years, including 102 asthmatic patients and 101 healthy control subjects were included in this study. The asthma group was divided into two groups as follows: Group I: Asthmatic children with positive family history for atopy (n=53), Group II: Asthmatic children without any family history for atopy (n=49). One hundred and twenty-eight atopic family members were also included in the study. The insertion/deletion (I/D) polymorphism of the ACE and PAI-1 4G/5G gene polymorphisms was carried out by polymerase chain reaction. Results: The prevalence of the PAI-1 4G allele was significantly greater in asthmatic children compared to control group (p<0.05, OR: 1.64 (1.11–2.43)) but there was no significant relation between ACE I/D genotypes and childhood asthma. No significant difference was detected between Groups I and II in terms of these ACE and PAI-1 genotypes and allele frequencies. No significant relationship was found between both gene polymorphisms and total serum IgE and skin prick test results. Conclusion: It has been established that PAI-1 4G allele may be a genetic risk factor for childhood asthma but ACE gene I/D polymorphisms do not play a role in the development of asthma in the sample of Turkish children(AU)

Plasminogen activator inhibitor-1 and angiotensin converting enzyme gene polymorphisms in Turkish asthmatic children.

BACKGROUND: Polymorphisms of plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes have been implicated in susceptibility to asthma. In this study, we aimed to investigate whether there was any association between childhood asthma and polymorphisms of the PAI-1 and ACE genes. METHODS: Two hundred and three Turkish children aged 5-15 years, including 102 asthmatic patients and 101 healthy control subjects were included in this study. The asthma group was divided into two groups as follows: Group I: Asthmatic children with positive family history for atopy (n=53), Group II: Asthmatic children without any family history for atopy (n=49). One hundred and twenty-eight atopic family members were also included in the study. The insertion/deletion (I/D) polymorphism of the ACE and PAI-1 4G/5G gene polymorphisms was carried out by polymerase chain reaction. RESULTS: The prevalence of the PAI-1 4G allele was significantly greater in asthmatic children compared to control group (p<0.05, OR: 1.64 (1.11-2.43)) but there was no significant relation between ACE I/D genotypes and childhood asthma. No significant difference was detected between Groups I and II in terms of these ACE and PAI-1 genotypes and allele frequencies. No significant relationship was found between both gene polymorphisms and total serum IgE and skin prick test results. CONCLUSION: It has been established that PAI-1 4G allele may be a genetic risk factor for childhood asthma but ACE gene I/D polymorphisms do not play a role in the development of asthma in the sample of Turkish children.