Anti-VEGF treatment suppresses remodeling factors and restores epithelial barrier function through the E-cadherin/ß-catenin signaling axis in experimental asthma models.

Besides maintaining a physical barrier with adherens junctional (AJ) and tight junctional proteins, airway epithelial cells have important roles in modulating the inflammatory processes of allergic asthma. E-cadherin and ß-catenin are the key AJ proteins that are involved in airway remodeling. Various mediators such as transforming growth factor-ß (TGF-ß), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), tumor necrosis factor-α (TNF-α) and angiogenic factors, such as vascular endothelial growth factor (VEGF), are released by the airway epithelium in allergic asthma. The signaling pathways activated by these growth factors trigger epithelial-mesenchymal transition (EMT), which contributes to fibrosis and subsequent downregulation of E-cadherin. The present study used a mouse asthma model to investigate the effects of anti-VEGF, anti-TNF and corticosteroid therapies on growth factor and E-cadherin/ß-catenin expression. The study used 38 male BALB/c mice, divided into 5 groups. A chronic mouse asthma model was created by treating 4 of the groups with inhaled and intraperitoneal ovalbumin (n= 8 per group). Saline, anti-TNF-α (etanercept), anti-VEGF (bevacizumab) or a corticosteroid (dexamethasone) were applied to each group by intraperitoneal injection. No medication was administered to the control group (n=6). Immunohistochemistry for E-cadherin, ß-catenin and growth factors was performed on lung tissues and protein expression levels assessed using H-scores. Statistically significant differences were observed in E-cadherin, ß-catenin, EGF, FG, and PFGF (P<0.001 for all) as well as the IGF H-scores between the five groups (P<0.005). Only anti-VEGF treatment caused E-cadherin and ß-catenin levels to increase to the level of non-asthmatic control groups (P>0.005). All treatment groups had reduced TGF-ß, PDGF and FGF H-scores in comparison with the untreated asthma group (P=0.001). The EGF and IGF levels were not significantly different between the untreated asthmatic and non-asthmatic controls. The results suggested that anti-VEGF and TNF-α inhibition treatments are effective in decreasing growth factors, in a similar manner to conventional corticosteroid treatments. Anti-VEGF and TNF inhibition therapy may be an effective treatment for remodeling in asthma while offering an alternative therapeutic option to steroid protective agents. The data suggested that anti-VEGF treatment offered greater restoration of the epithelial barrier than both anti-TNF-α and corticosteroid treatment.

Vitamin D deficiency negatively affects both the intestinal epithelial integrity and bone metabolism in children with Celiac disease.

BACKGROUND AND AIM: We aim to evaluate serum vitamin D levels, vitamin D receptor (VDR) expression in the intestinal epithelium, and their relation with epithelial barrier proteins and bone metabolism in children with Celiac disease (CD). METHODS: Immunostaining for VDR, Claudin-2 and E-cadherin was performed in duodenal samples of the patients with CD and controls. H-score [∑Pi(I+1)] where I is the intensity score and Pi is the corresponding percentage of stained cells was calculated for each samples. The clinic, laboratory and histopathological findings were compared between patients and controls. RESULTS: Thirty-six patients with CD and age and sex matched 36 controls were enrolled. 25-OH vitamin D levels were significantly lower in the patient group compared to the control group. The mean bone mineral density (BMD) value was significantly lower in patients with vitamin D deficiency compared to patients with normal vitamin D level. H-scores for both VDR and Claudin-2 were significantly lower in patient group when compared to the control group. H-scores for VDR, Claudin-2 and E-cadherin were significantly lower in patients with vitamin D deficiency compared to patients with normal vitamin D level. There were positive correlations between 25-OH vitamin D level and H-scores for VDR, E-cadherin and Claudin-2 in patient group. CONCLUSIONS: Our findings showed that vitamin D deficiency is common among children with CD. Expression of VDR and epithelial barrier proteins Claudin-2 and E-cadherin which have important roles in paracellular pathway, was decreased in children with CD in correlation with histological findings of disease severity. Furthermore, deficiency of vitamin D was related to decreased expression of VDR and epithelial barrier proteins E-cadherin and Claudin-2. These findings indicate that paracellular pathway structures responsible for calcium absorption are disturbed in CD which is aggravated by vitamin D deficiency.

Safety of subcutaneous allergen immunotherapy in children: A retrospective review and bird eye to literature.

Toprak-Kanik E, Yilmaz Ö, Yangin-Ergon E, Türkeli A, Yüksel H. Safety of subcutaneous allergen immunotherapy in children: A retrospective review and bird eye to literature. Turk J Pediatr 2018; 60: 684-690. Subcutaneous allergen immunotherapy (SCIT) has been shown to improve clinical course in children with asthma and allergic rhinitis (AR). Systemic and local side-effects may be seen during its administration. The purpose of this study was to evaluate risk factors associated with systemic and local side-effects in children receiving SCIT. We performed a retrospective chart review in the children who received allergen subcutaneous immunotherapy for asthma and/or allergen rhinitis. Demographic data, diagnosis, skin prick test results, presence of additional allergic diseases, the seasonal variation of adverse events in the first and third years of SCIT were recorded. A total of 508 eligible patients were included in the study. Mean age of the children was 10.9±3.2 years, and 65.4% were male. Asthma was present in 21.9% of the children, AR in 44.7%, 33.5% of them had both asthma and AR. According to the skin prick test results, sensitivity to more than one allergen was present in 45.1%, while the most common single-allergen sensitivities were to grass pollen and dermatophagoids (32.5% and 14.4%, respectively). Ratio of systemic and local side-effects was 4.7% and 9.3%, respectively. Local side-effects were more common than systemic reaction. SCIT is a safe treatment modality while using the appropriate dose and with the administration of dose-escalation protocol.

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

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.

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

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.

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

Yilmaz 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.

Metered dose inhaler-spacer use education effects on achieve asthma control in children.

INTRODUCTION: Improper Metered Dose Inhaler (MDI)-spacer use technique can result in less than optimal delivery of medicine to the lungs and poor asthma outcomes. The aim of this study was to evaluate the influence of standardized education on proper MDI- spacer use and asthma control in children with asthma and to identify the factors associated with these results. MATERIALS AND METHODS: This is a cohort study that evaluated the influence of standardized education about MDI-Spacer device use on asthma control in children. Asthmatic children using MDI-Spacer device and their parents were enrolled in this study. Children were followed up for two months after standardized education and the change in asthma control was recorded. RESULT: Thirty eight children (14 females and 24 males) aged between 2.5 and 13 years were enrolled in the study. Mean age of the children was 7.5 ± 2.8 years. Six patients were lost to follow up and thirty two patients completed the study. Mean inhalation technique score was 4.9 ± 1.3 before education and increased significantly to 7.8 ± 0.4 after education (p< 0.001). Mean Asthma Control Questionnaire (ACQ) score decreased significantly with education (0.77 ± 0.9 vs 0.1 ± 0.1 respectively, p< 0.001). Similarly, mean asthma symptom score (ASS) decreased significantly from 4.3 ± 3.6 to 0.2 ± 0.7 with education (p< 0.001). Most common mistake in use of MDI-Spacer device use was detected to be lack of mouth rinsing after use before education in 78.9% of the patients. CONCLUSIONS: Providing standardized education about MDI-Spacer device use to children and parents leads to correct MDI-Spacer device use and is associated with improvement in asthma symptom score and asthma control.

The Effect of Flexible Bronchoscopy on Anxiety in Children.

OBJECTIVES: Flexible bronchoscopy (FB) is a semi-invasive diagnostic tool that allows direct visualization of the airways. The use for diagnostic and therapeutic purposes in children is incrasing with the developments in modern anesthesia. Irrespective of the type of the invasive diagnostic procedure, these interventions are known to cause anxiety in patients. The aim of our study was to evaluate the anxiety and depression status in children hospitalized for bronchoscopy and to investigate the effects of FB. MATERIAL AND METHODS: Thirty children hospitalized for FB and 30 controls, aged 7 to 16 years, were enrolled in this study. Anxiety was evaluated with the "Hospital anxiety and depression scale" (HADS)" besides other parameters recorded. RESULTS: The mean HADS anxiety scores in the patient and control groups were respectively 10.1 (3.5) and 2.7 (1.3) (p= 0.001). The mean HADS depression scores were respectively 8.8 (3.7) and 2.2 (1.1) (p= 0.001). Among the patients, 50% had anxiety and 53.3% had findings while none in the control group showed signs of anxiety and depression. A positive correlation was found between the age and, anxiety and depression scores in patients' groups (respectively r1= 0.257; p= 0.05 and r2= 0.288; p= 0.02). CONCLUSION: Anxiety was demonstrated in nearly half of the children hospitalized for bronchoscopy. It has been observed that behavioral and physical problems may be encountered in approximately 40-60% of children who feel generalized anxiety before anesthesia, during the preoperative, postoperative period, and subsequent periods. These results suggest that the detection of children with increased anxiety and indicate the individual requirements can be assisted pharmacological and psychological supports.

Vascular endothelial growth factor antagonism restores epithelial barrier dysfunction via affecting zonula occludens proteins.

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.

IL-5, IL-8 and MMP -9 levels in exhaled breath condensate of atopic and nonatopic asthmatic children.

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.

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.

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. 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.

Is obesity related to worse control in children with asthma?

INTRODUCTION: Asthma and obesity are related diseases however the influence of obesity on asthma severity is not clear yet. Therefore, the aim of our study was to evaluate the association between obesity and asthma control evaluated on the basis of symptoms and asthma control questionnaire (ACQ). MATERIALS AND METHODS: We enrolled 98 children with asthma aged 4 to 14 years consecutively and recorded their disease characteristics and severity parameters as well as the symptom scores. All children filled in the ACQ. Children were classified as obese and non-obese according to body mass index. Obesity was defined as body mass index over 90th percentile. RESULTS: Mean age of the children in the obese group (n= 27) was 8.1 ± 2.6 while that in the non-obese group (n= 71) was 8.6 ± 2.9 (p= 0.41). Asthma symptom score in obese and non-obese groups were not significantly different (p= 0.73). Children in the obese group had lower ACQ scores when compared to the non-obese group (1.2 ± 0.9 vs 1.7 ± 1.0, p= 0.04) however this significance was lost when controlled for age and gender in the regression model. CONCLUSION: The results of this study suggest that obesity is not significantly associated with worse asthma control when adjusted for age and gender.

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.

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.

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.

Peripheral Mononuclear Response to Antigenic Stimulation in Children with Obese Asthma Phenotype.

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)-ß 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-ß 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-ß 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.