Browsing by Author "Turkeli A."
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Item Peripheral mononuclear response to antigenic stimulation in children with obese Asthma Phenotype(2013) Yuksel H.; Yilmaz O.; Vatansever S.; Onur E.; Kirmaz C.; Nal E.; Turkeli A.; Bozyigit F.D.An investigation of immunopathogenetic mechanisms of obesity-associated asthma may demonstrate novel therapeutic targets. The aim of this study was to compare levels of T-helper lymphocyte (Th)1, Th2, regulatory T lymphocyte (Treg), and Th17 cytokines secreted by peripheral blood mononuclear cell culture (PBMC) in response to nonspecific stimulation in obese and nonobese children with asthma. Obese and nonobese children with asthma aged 5-16 were enrolled into this case-control study consecutively. Age at asthma diagnosis and clinical severity were recorded. A skin prick test was performed. Serum adipokine levels and PBMC supernatant interleukin (IL)-4, IL-10, IL-17, IL-23, interferon (IFN)γ, and transforming growth factor (TGF)-β levels were measured. Mean (±standard deviation) ages of obese (n=28) and nonobese (n=39) children with asthma were 8.7±2.9 and 10.5±3.2, respectively. Asthma symptom score was higher, and age at asthma diagnosis was lower in obese compared with nonobese children with asthma (P=0.03 and P=0.004, respectively). Leptin levels were significantly higher in obese than in nonobese asthma group (P<0.001). IL-10 and IL-17 levels in obese group were significantly lower than in nonobese group (P=0.005 and P=0.017, respectively). On the other hand, TGF-β levels were significantly higher in obese compared with nonobese children with asthma (P=0.015). IL-4, IL-23, and IFNγ levels were not significantly different between the groups (P<0.05 for all). Low IL-10 and high TGF-β levels in obese compared with nonobese children with asthma might indicate lower anti-inflammatory cytokine secretion and Treg function as well as a higher remodeling process in obesity-associated asthma in children. © 2013 Mary Ann Liebert, Inc.Item Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma(2013) Yilmaz O.; Karaman M.; Bagriyanik H.A.; Firinci F.; Kiray M.; Turkeli A.; Karaman O.; Yuksel H.Background The aim of the study was to compare the influence of TNF antagonism and corticosteroid treatment on epithelial, smooth muscle and basement membrane component of airway remodeling in an experimental murine model of chronic asthma. Methods We used 30 BALB/c mice. Group 1 not exposed to ovalbumin or any medication was designated as control group. Chronic asthma model was achieved in the other three groups with intraperitoneal (IP) and inhaled ovalbumin. Then, Group 2 received IP saline, Group 3 received IP dexamethasone and Group 4 received IP etanercept. Epithelial, subepithelial smooth muscle and basement membrane thickness as well as goblet cells and mast cells were examined on samples isolated from left lung. Results Etanercept treatment led to thinner epithelial and basement membrane layer and lower goblet and mast cell number than untreated asthmatic mice (p < 0.001, p = 0.001, p = 0.005 and p = 0.03 respectively). Neither epithelial and basement membrane thickness nor mast cell number was different among mice treated with etanercept and dexamethasone (p = 0.38, p = 0.79 and p = 0.51 respectively). However, etanercept group was associated with thicker subepithelial muscle layer but lower goblet cell number (p < 0.001 and p = 0.04 respectively) than dexamethasone group. Conclusions Corticosteroids are more effective in decreasing smooth muscle mass while TNF antagonists in reducing goblet cell number in animal model of asthma. Therefore, further research is needed to assess the synergistic use of TNF antagonism and dexamethasone for more rational remodeling control. © 2013 Elsevier B.V.Item Role of vascular endothelial growth factor antagonism on airway remodeling in asthma(2013) Yuksel H.; Yilmaz O.; Karaman M.; Bagriyanik H.A.; Firinci F.; Kiray M.; Turkeli A.; Karaman O.Background: Vascular endothelial growth factor (VEGF) is an important mediator of the neoangiogenesis component of remodeling in asthma. Objective: To evaluate the influence of VEGF blockage on airway remodeling, specifically epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness, in a mouse model of chronic asthma. Methods: We used 30 BALB/c mice. The control group was not exposed to ovalbumin or any medication (group 1). Other groups were exposed to intraperitoneal and inhaled ovalbumin to achieve chronic asthma. Each of these groups received intraperitoneal saline (group 2), intraperitoneal dexamethasone (group 3), or intraperitoneal bevacizumab (group 4). Histomorphologic examination for epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness was performed from the middle zone of the left lung. Results: Treatment with anti-VEGF caused significant reduction in epithelial, subepithelial muscle, and basement membrane thickness compared with untreated asthmatic mice (P =.001, P =.03, and P =.009, respectively). Goblet and mast cell numbers were significantly lower in mice treated with anti-VEGF than in untreated mice (P =.02 and P =.007, respectively). Dexamethasone treatment resulted in improvement of all histomorphologic markers, except goblet cell number. Influences of dexamethasone and anti-VEGF on epithelial and basement membrane thickness and mast and goblet cell numbers did not differ (P >.05), but subepithelial muscle layer was thinner in the former (P =.003). Conclusion: VEGF blockage may provide adjunctive therapeutic options as steroid-sparing agents for more effective treatment of remodeling in asthma. © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.Item E-cadherin as an epithelial barrier protein in exhaled breath condensate(Institute of Physics Publishing, 2014) Yuksel H.; Turkeli A.; Taneli F.; Horasan G.D.; Kanik E.T.; Kizilkaya M.; Gozukara C.; Yilmaz O.Airway epithelium plays an important role as a physical barrier and a modulator of allergic response. Junctions between cells provide epithelial integrity and barrier function. The aim of this study was to investigate the influence of atopy on airway epithelial integrity in asthma and to measure E-cadherin levels in exhaled breath condensate as an indicator epithelial damage. A total of 74 patients with asthma (35 atopic and 39 non-atopic) and 39 healthy children were enrolled in this case-control study. Sociodemographic characteristics and asthma severity parameters in the last three-month period were recorded and pulmonary function tests were performed. Blood samples were obtained to measure serum immunoglobulin E (IgE) levels and peripheral blood eosinophil count, and exhaled breath condensate (EBC) was obtained to measure E-cadherin. EBC E-cadherin levels were significantly lower in the asthmatics when compared to non-atopic controls (0.109 (0.076) versus 0.191 (0.184) ng mL-1 respectively, p = 0.01). Atopic and non-atopic asthmatic groups had lower EBC E-cadherin levels compared to the control group. (0.112 (0.060) ng ml-1, 0.106 (0.089) ng ml-1 and 0.191 (0.184) ng ml-1, p = 0.02 and p < 0.01 respectively). However, EBC E-cadherin levels were not different between atopic and non-atopic asthmatics. The results of our study support the role of E-cadherin in the pathogenesis of asthma. However, the absence of difference in E-cadherin levels between atopic and non-atopic asthmatics suggests that allergic sensitization is not the primary factor for development of epithelial barrier dysfunction in asthma. © 2014 IOP Publishing Ltd.Item Predictive value of the TRACK questionnaire as a measure of asthma control in preschool aged children(Korean Academy of Asthma, Allergy and Clinical Immunology, 2014) Yilmaz O.; Turkeli A.; Sahin S.; Yuksel H.Assessment of asthma control in preschool children is important for therapeutic decisions. Aim of this study was to evaluate the predictive value of TRACK questionnaire scores for subsequent clinical parameters and to investigate the validity and reliability of the Turkish version of the TRACK questionnaire. We enrolled 100 children with asthma aged 4 years or younger in this cohort study. We recorded sociodemographic characteristics and clinical severity parameters. A pediatric allergist filled in the asthma severity scale and the caregiver of the child filled in the TRACK questionnaire. We called in the children again at the end of one month and recorded the same parameters and administered TRACK again. Uncontrolled asthma was defined as a TRACK score below 80. According to the TRACK score, 65% of the children had controlled asthma initially while at the end of the study 64.1% had controlled asthma. At the beginning of the study, all clinical parameters were worse in children with uncontrolled asthma according to TRACK score. Similarly, other objective clinical parameters during the following one month period were worse in children with initial uncontrolled asthma. Cronbach's alpha score for the TRACK questionnaire was 0.84. Turkish TRACK questionnaire is a valid and reliable tool that is predictive of short term asthma prognosis. © Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology.Item IL-5, IL-8 and MMP -9 levels in exhaled breath condensate of atopic and nonatopic asthmatic children(W.B. Saunders Ltd, 2015) Turkeli A.; Yilmaz O.; Taneli F.; Horasan G.D.; Kanik E.T.; Kizilkaya M.; Gozukara C.; Yuksel H.Rationale Asthma is a heterogeneous disease, and a great majority of pediatric patients with asthma demonstrate atopic characteristics and develop a Th2 type cytokine response. Nonatopic asthma, on the other hand, is seen more rarely. Methods In this study, levels of IL-5, IL-8 and MMP-9 were measured in exhaled breath condensate (EBC) of the subjects to demonstrate the extent of tissue damage as well as eosinophilic and neutrophilic inflammation in children with atopic and nonatopic asthma. A total of 37 children with atopic asthma and 37 children with nonatopic asthma were enrolled in the study. Patients who exhibited protease positive aeroallergen (House dust mite, mould mix, olea, grass mix) sensitivity in allergen skin prick test were included in the atopic asthma group. To evaluate the EBC, the fluid content of the breath was collected by having the patients exhale into an EBC device, after which the IL-5, IL-8 and MMP-9 levels were assayed using the ELISA method. Results The atopic asthmatics exhibited significantly higher IL-5 levels in their EBC samples than the nonatopic asthmatics (0.271 [0.198-0.489] pg/ml and 0.198 [0.125-0.344] pg/ml, respectively, p = 0.04), while no significant differences were observed in the levels of IL-8 and MMP-9 in the EBC samples of the atopic and nonatopic asthmatics. Conclusions IL-5 levels, as a marker of eosinophilic inflammation, were demonstrated to be higher in the children with atopic asthma when compared to those with nonatopic asthma in EBC. The fact that no significant difference was apparent in the IL-8 levels between the groups suggests that it is the severity of the disease rather than the atopic state that plays an important role in IL-8 levels. Since no difference was recorded between the groups in terms of MMP-9 levels, lung damage in asthma sufferers seems to develop independent of atopia. © 2015 Elsevier Ltd.Item Vascular endothelial growth factor antagonism restores epithelial barrier dysfunction via affecting zonula occludens proteins(Spandidos Publications, 2015) Yuksel H.; Yilmaz O.; Karaman M.; Firinci F.; Turkeli A.; Kanik E.T.; Inan S.Epithelial barrier dysfunction is important in the pathogenesis of asthma and allergic responses, and is therefore a therapeutic target. The aim of the present study was to investigate the effects of dexamethasone, a classic therapeutic agent, an anti-tumor necrosis factor agent (etanercept), which is used to treat difficult cases of asthma, and an anti-vascular endothelial growth factor (VEGF) agent (bevacizumab), which is an angiogenesis inhibitor, on zonula occludens (ZO) proteins in an experimental asthma model. The experimental model of asthma was developed using intraperitoneal (IP) and inhaled administration of ovalbumin in 38 BALB/c mice, which were divided into four groups. The control group (n=6) did not receive any treatment, while the four remaining groups (n=8 per group) received an IP injection of saline, etanercept, bevacizumab or dexamethasone, respectively. Occludin, claudin and junctional adhesion molecule (JAM) were immunohistochemically stained in the left middle lobe samples using an indirect avidin-peroxidase method, after which the staining was semiquantified with H-scores. Statistically significant differences were observed in the occludin, claudin and JAM H-scores among the four groups (P<0.001). In the untreated asthma, etanercept, bevacizumab and dexamethasone groups, the median H-scores for occludin were 93, 177, 280 and 198, respectively, while the H-scores for claudin were 82, 193.5, 274 and 202.5, respectively, and the median H-scores for JAM were 130, 210, 288 and 210, respectively. Pairwise comparisons revealed that all three ZO protein H-scores were significantly lower in the saline group when compared with each treatment group. However, the H-scores of the ZO proteins were not significantly different between the etanercept and dexamethasone groups. Furthermore, the bevacizumab group exhibited higher H-scores for all the proteins compared with the dexamethasone group. Therefore, antagonism of VEGF with bevacizumab restores the epithelial barrier to a greater extent when compared with dexamethasone treatment. This result may be promising for the development of novel therapeutic agents. © 2015, Spandidos Publications. All rights reserved.Item Effects of Vitamin D levels on asthma control and severity in pre-school children(Verduci Editore, 2016) Turkeli A.; Ayaz O.; Uncu A.; Ozhan B.; Bas V.N.; Tufan A.K.; Yilmaz O.; Yuksel H.OBJECTIVE: Prevalence of asthma and Vitamin D deficiency has been increasing and leading to significant morbidities. This study aimed to compare the Vitamin D levels in the pre-school children with asthma and in healthy controls and to assess the relationship between Vitamin D levels and asthma clinical parameters and control. PATIENTS AND METHODS: Vi tamin D [25(OH)D3] levels were measured in 102 preschool children, aged 1-4 years with asthma and 102 healthy controls in winter. The patients with asthma were grouped according to serum Vitamin D levels as sufficient, insufficient and deficient. Asthma control was classified according to the Global Initiative for Asthma (GINA) guidelines and the Test for Respiratory and Asthma Control in Kids (TRACK) in 1-4 years-old children. RESULTS: Serum Vitamin D levels were 22.64 (9.96) ng/ml in the asthma group and 32.11 (14.74) ng/ml in the control group (p = 0.001). Total number of exacerbations during the previous year were significantly lower in the Vitamin D sufficient group, compared to the deficient and insufficient groups (p = 0.03). Frequency of patients with controlled asthma was higher in the sufficient group compared to the deficient and insufficient groups (p = 0.001 and p = 0.001, respectively). There was a positive correlation between serum Vitamin D levels and asthma control. CONCLUSIONS: The frequency of Vitamin D deficiency and insufficiency was higher in children with asthma, compared to the controls. Therefore, we suggest that lower levels of Vitamin D are associated with poor asthma control and increased asthma severity.Item Airway epithelial barrier dysfunction in the pathogenesis and prognosis of respiratory tract diseases in childhood and adulthood(Taylor and Francis Inc., 2017) Yuksel H.; Turkeli A.The lungs are in direct contact with the environment through the tubular structure that constitutes the airway. Starting from the nasal orifice, the airway is exposed to foreign particles including infectious agents, allergens, and other substances that can damage the airways. Therefore, the airway must have a functional epithelial barrier both in the upper and lower airways to protect against these threats. As with the skin, it is likely that the pathogenesis of respiratory diseases is a consequence of epithelial barrier defects in these airways. The characteristics of this system, starting from the beginning of life and extending into maturing and aging, determine the prognosis of respiratory diseases. In this article, we discuss the pathogenesis, clinical phenotype, and prognosis of respiratory diseases from newborns to adulthood in the context of epithelial barrier function and dysfunction. © 2017 Taylor & Francis.Item Secondhand tobacco smoke and severity in wheezing children: Nasal oxidant stress and inflammation(Taylor and Francis Ltd, 2018) Yilmaz O.; Turkeli A.; Onur E.; Bilge S.; Yuksel H.Objectives: Prenatal and postnatal smoke exposures are associated with many lung diseases in children due to impaired lung function, increased inflammation, and oxidative stress. We aimed to determine the influence of secondhand tobacco smoke exposure on the levels of nasal glutathione, IL-8, IL-17, MMP-9, and TIMP-1, as well as serum surfactant protein-D (SP-D) in wheezy children. Methods: We enrolled 150 children with recurrent wheezing and recorded wheezing characteristics at enrollment. We measured the levels of serum cotinine, SP-D, nasal glutathione, IL-8, IL-17, MMP-9, and TIMP-1. Serum cotinine levels between 3 and 12 ng/mL, and above 12 ng/mL were defined as lower and higher level secondhand tobacco smoke exposure, respectively. The ANOVA test, Pearson's correlation analysis and multivariate analysis with a linear regression test were used for the statistical analysis. Results: Ninety-one children had been exposed to lower level secondhand tobacco smoke, while 24 children were exposed to higher level secondhand tobacco smoke. Thirty-five children were not exposed to cigarette smoke. Wheezing symptom scores were higher in exposed children (p = 0.03). Levels of other biomarkers showed no significant difference. Conclusions: Secondhand tobacco smoke exposure is associated with more severe respiratory symptoms in wheezing children. However, levels of nasal or serum inflammatory markers fail to explain this association, either because of different mechanical factors in the process or due to low levels of the biomarkers especially in nasal secretions. © 2018 Taylor & Francis Group, LLC.Item Low Mononuclear Cell IL-18 and IL-27 Response in Children: Susceptibility to Tuberculosis Infection after Contact(Georg Thieme Verlag, 2019) Karabacak H.A.; Yilmaz O.; Tuglu I.; Taneli F.; Surucuoglu S.; Kanik E.T.; Ozkutuk N.; Gozukara C.; Ozkut M.M.; Turkeli A.; Yuksel H.Background Identification of the immune response against tuberculosis is vital to develop new diagnostic and therapeutic modalities. The objective of this study was to determine IL (interleukin)-18 and IL-27 responses of peripheral blood mononuclear cells to early secreted antigen (ESAT-6) and culture filtrate protein-10 (CFP-10) stimulation in children with a (+) or (-) tuberculin skin test (TST) with in-house tuberculosis contact. Methods We enrolled 40 children aged 1 to 5 years who had an in-house contact with a tuberculous adult. Blood samples were obtained from all children for QuantiFERON tuberculosis (TB) gold in tube (QFT-GIT), and peripheral blood mononuclear blood cell culture tests. The subjects were grouped as TST (-) QFT-GIT (-), TST (+) QFT-GIT (-), and TST (+) QFT-GIT (+). Supernatant of peripheral blood mononuclear cell culture was separated with and without stimulation of ESAT-6 and CFP-10, and IL-18 and IL-27 levels were measured with enzyme linked immunoassay (ELISA) test. Results The study group included 22 boys and 18 girls with mean age 4.25 ± 0.9 years. IL-18 and IL-27 levels were statistically significant in ESAT-6/CFP-10-stimulated supernatants of peripheral blood mononuclear cell (PBMC) samples among the three groups (p = 0.000, p = 0.007, respectively). IL-18 levels between the TST (-) QFT-GIT (-) and TST (+) QFT-GIT (+) groups were significantly different (p = 0.026). Both IL-18 and IL-27 levels were significantly different between ESAT-6/CFP-10 stimulated PBMC supernatants of TST (-) QFT-GIT (-) and TST (+) QFT-GIT (-) groups (p = 0.000, p = 0.003, respectively). Conclusion Low IL-18 and IL-27 responses of peripheral blood mononuclear cells in children with Bacillus Calmette-Guérin (BCG) vaccine may play a role in Mycobacterium tuberculosis infection after in-house contact. © 2019 by Georg Thieme Verlag KG, Stuttgart. New York.