Ahmet Turkeli

Role of vascular endothelial growth factor antagonism on airway remodeling in asthma.

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.

Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma.

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.

E-cadherin as an epithelial barrier protein in exhaled breath condensate

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.

Airway epithelial barrier dysfunction in the pathogenesis and prognosis of respiratory tract diseases in childhood and adulthood

ABSTRACT 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.

Predictive Value of the TRACK Questionnaire as a Measure of Asthma Control in Preschool Aged Children

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. Cronbachs 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.

Secondhand tobacco smoke and severity in wheezing children: Nasal oxidant stress and inflammation

ABSTRACT 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, Pearsons 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.

Does having an asthmatic sibling affect the quality of life in children

Yılmaz Ö, Türkeli A, Karaca Ö, Yüksel H. Does having an asthmatic sibling affect the quality of life in children? Turk J Pediatr 2017; 59: 274-280. Chronic illness in a family member leads to deterioration of quality of life in other members of that family. We aimed to investigate the influence of having an asthmatic sibling on a child`s quality of life (QoL). We enrolled 2-12 year aged healthy children with an asthmatic sibling in the study group and healthy children with a healthy sibling in the control group of this cross-sectional study. Sociodemographic characteristics of children and disease severity characteristics of asthmatic siblings were recorded. All parents filled in Turkish generic PedsQLTM short form appropriate for the child`s age group. Study and control groups had 114 children each. Total PedsQLTM scores were not significantly different in any of the age groups (p=0.23, p=0.13, p= 0.11 respectively). Emotional PedsQLTM sub-scores in children with an asthmatic sibling were significantly worse (83.0±16.5 vs 91.6±10.9 in the 2-4 year age group, 72.0±17.8 vs 92.2±11.6 in the 5-7 year age group, 73.7±24.1 vs 88.7±14.8 in the 8-12 year age group respectively, p≤0.002 for all). Similarly, psychosocial sub-score was significantly lower in the 2-4 and 5-7-year-olds but not the 8-12 year old groups (p=0.01, p=0.01, p=0.08 respectively). In conclusion, healthy children with asthmatic siblings have significantly lower emotional QoL and this needs to investigated for other chronic diseases in further research.

Follicular bronchiolitis: a rare disease in children.

Follicular bronchiolitis (FB) is a benign progressive lung disease. It is characterized with lymphoplasmocellular infiltration and hyperplastic follicles in the peribronchial areas in the small airways. Follicular bronchiolitis should be considered in cases where chronic cough, recurrent upper respiratory tract infections and progressive dyspnea are observed in children. The diagnosis should be supported by lung biopsy. A 8-year old female patient presented to our hospital with complaints including continuing cough and wheezing. Bilateral extensive rales and rhonchi in the lungs were heard on auscultation and lung graphy revealed reticuloglandular appearance. Bilateral extensive septal thickennings, reticulonodular appearance, patchy bronchiectasis, bronchiolectasis and peribronchial thickennings were found on high-resolution thoracal computarized tomography. A diagnosis of follicular bronchiolitis was made as a result of lung biopsy. Improvement was observed in the complaints and findings of our patient after methylprednisolone treatment. This patient was presented to emphasize rare interstitial lung diseases should also be considered in children who present with a clinical picture of chronic bronchial obstruction and do not respond to standard treatment.