Ozlem Yilmaz Ozbek

Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in Turkish children with asthma and allergic rhinitis

Plasminogen activator inhibitor (PAI-1) has an essential role in tissue remodeling after inflammation. Recent literature revealed only one study evaluating PAI-1 4G/5G gene polymorphism in children with asthma and none in children with allergic rhinitis. We aimed to investigate distribution of PAI-1 4G/5G polymorphism in a group of Turkish children with asthma and allergic rhinitis and compare these findings with those obtained in normal peers. Patients with physician-diagnosed asthma (n = 106) and allergic rhinitis (n = 99) and 83 healthy peers were included in this study. We evaluated PAI-1 4G/5G polymorphism genotype as well as the possible association between PAI-1 4G/5G polymorphism and pulmonary function tests, serum total immunoglobulin E (IgE), total eosinophil count, and skin-prick test positivity in our study. The prevalence of the 4G allele significantly exceeded the values found in the controls both in patients with asthma (p = 0.001) and in patients with allergic rhinitis (p = 0.002). Interestingly, comparison of asthmatic patients revealed that mean baseline percent forced expiratory volume in 1 second and forced vital capacity were significantly higher in patients who bear 5G/5G genotype than in those who have 4G/4G or 4G/5G genotypes. No statistically significant relationship were found between PAI-1 polymorphism and total serum IgE levels, total eosinophil count, or selected skin test responses to aeroallergens. Our study suggests that Turkish children with asthma or allergic rhinitis have a higher prevalence of PAI-1 4G allele compared with their healthy peers.

Evaluation of angiopoietin 1 and 2, vascular endothelial growth factor, and tumor necrosis factor alpha levels in asthmatic children.

Asthma is characterized by chronic airway inflammation that is associated with structural changes termed airway remodeling. Recently, cytokines/mediators that augment inflammation have been attracting attention in this field. The aim of this study was to evaluate serum angiopoietin (Ang)-1, Ang-2, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF) alpha values, which have important roles in inflammation, angiogenesis, and remodeling in asthmatic children. We also documented correlations between demographic features, duration of asthma, and pulmonary function test (PFT) parameters. Randomly selected 40 children (20 male and 20 female children, aged 6-16 years) with mild or moderate persistent asthma and 32 healthy children (15 male and 17 female children, aged 6-16 years) enrolled in the study. All asthmatic children had been using inhaled corticosteroids at least for the last 3 months. Serum Ang-1 levels were significantly lower in asthmatic children than those in normal controls. The Ang-1/Ang-2 ratio was also significantly lower in asthmatic children compared with those in normal controls (p < 0.01). However, serum Ang-2, VEGF, and TNF-alpha levels were similar in the two groups. A significant positive correlation was found between VEGF and duration of asthma. No correlation between serum Ang-1, Ang-2, VEGF values, and PFT parameters was obtained. On the other hand, significant negative correlation was detected between serum TNF-alpha and forced expiratory volume in 1 second. We have shown that serum Ang-1 levels and Ang-1/Ang-2 ratio were significantly reduced and balance was toward Ang-2 in asthmatics children. This process may lead to inflammation, destabilization of blood vessels, and trigger remodeling.

Double invasive fungal infection and typhlitis in children with acute lymphoblastic leukemia.

Invasive fungal infection is one of the major causes of morbidity and mortality in immunocompromised patients. The occurrence of two invasive fungal infections in one patient at the same time is quite rare. Here the authors report on two adolescent patients with acute lymphoblastic leukemia who developed combined invasive pulmonary aspergillosis and hepatosplenic candidiasis during chemotherapy. They were treated with liposomal amphotericin B, but one of them died due to massive pulmonary hemorrhage during recovery from neutropenia.

Angiopoietin 1 and 2 levels in inhaled steroid using children with stable asthma

lished in the Annals of Allergy, Asthma, and Immunology. The authors analyzed plasma angiopoietin-1 (Ang1) and Ang2 levels in patients with exacerbated asthma and stable asthma before starting use of medication. The study included adults, and the mean (SD) duration of asthma was 6.63 (3.6) years. They found that plasma Ang2 levels were higher and Ang1 levels were lower in patients with exacebated asthma than in those with stable asthma. Plasma Ang2 levels were decreased in patients with stable asthma compared with healthy controls; however, no difference was found in Ang1 levels between patients with stable asthma and healthy controls. They also found that circulating Ang1 and Ang2 levels were correlated with the lung functions. In our recent study, we evaluated serumAng1 and Ang2 levels in children with asthma compared with healthy controls.2 We found that serum Ang2 levels in children with stable asthma were not different than in healthy controls, and we did not find a correlation between Ang levels and lung functions. Our patients were all using inhaled steroids and had stable asthma. We think that steroids help to control not only Ang2 levels but also lung function. Our study included children using inhaled steorids, and the mean (SD) duration of asthma was 27.2 (23.3) months, which was lower than the level found in the the work of Lee et al,1 supporting that finding that age, duration of disease, and medication may have effect on Ang levels. On the other hand, we found that Ang1 levels and the Ang1/ Ang2 ratio were significantly lower in children with asthma compared with healthy controls, which was similar to the findings of the previous work that found Ang1 levels to be decreased inmice with asthma.3 Simoes et al3 speculated that during asthma, after an initial decrease, Ang1 levels increase to provide vascular integrity.

Serum vitamin D levels decrease in children with acute urticaria.

BACKGROUND Acute urticaria is an immune-inflammatory disease, characterised by acute immune activation. There has been increasing evidence showing that vitamin D deficiency is associated with increased incidence and severity of immune-inflammatory disorders. OBJECTIVE The aim of this study was to evaluate serum vitamin D levels in acute urticaria. METHODS We enrolled 30 children with acute urticaria and 30 control subjects. Concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D status, were measured in serum of acute urticaria patients and compared with the control group. RESULTS There were no significant differences in baseline variables (age, gender, weight) between the groups. Vitamin D deficiency (<20ng/ml) was significantly higher in patients with acute urticaria than in control patients. Serum 25(OH)D levels were significantly lower in the study group compared to those in the control group (13.1±4.3 vs 28.2±7.4ng/mL, p<0.05). Moreover, we found negative correlation between mean duration of acute urticaria and serum vitamin D levels (p<0.01). CONCLUSION This study revealed a significant association of lower serum 25(OH)D concentrations with acute urticaria and an inverse relationship with disease duration. These findings may open up the possibility of the clinical use of vitamin D as a contributing factor in the pathogenesis of acute urticaria and a predictive marker for disease activity in acute urticaria. A potential role of vitamin D in pathogenesis and additive therapy in acute urticaria needs to be examined.

Long-term outcome of food allergy after liver transplantation in children.

Pediatric IgE-dependent food allergy (FA) after orthotopic liver transplantation (LT) is a wellknown complication; however, long-term prognosis of the patients who developed FA is unknown. In a recent study published elsewhere, we detected FA in six of 28 children who had LT (1). As long-term outcome of children who developed FA after LT has not been well established, we decided to follow these children in terms of FA after completion of the mentioned study in 2009. During the five-yr follow-up period, all 28 children who had LT visited the Pediatric Allergy Unit every three months. A detailed history of incriminated food (IF) was obtained. We also looked for a new-onset FA. Skin prick test results for the IFs and specific IgE levels were obtained every six months in patients who had FA. Table 1 shows demographic data of the patients. During the follow-up of five yr, new-onset FA has been noticed neither in children who had FA nor in those who had no FA after LT. Elimination of IF allergens from the diet has been continued systematically in all cases. By means of elimination, allergic symptoms did not return. Meanwhile, a decrease in serum-specific IgE levels was observed in all patients who had FA. An oral challenge with each IF was performed after obtaining negative serum-specific IgE levels and skin prick test responses. The IFs were successfully reintroduced in four children (patients 1, 2, 3, and 6) during 7–38 months after the introduction of elimination diet. In patient 6, an oral challenge was performed while the level of cow’s milk-specific IgE was slightly above the normal levels (4.95 UI/mL). In patient 4, lentil allergy, and in patient 5, milk (specific IgE: 74 UI/mL) and peach allergy could not be eliminated (Table 1). Patient 4 developed allergic asthma at the age of four yr, two yr after she developed FA.

Cows milk protein enteropathy and granulomatous duodenitis in a newborn

Abstract:  Cow’s milk protein enteropathy is a symptom complex that composed of severe diarrhoea and malnutrition. This disorder is caused by non‐immunoglobulin E‐mediated food allergy. Its clinical features and natural course have been explained in many reports, of different types of cow’s milk and soy reactions. In the present article, we describe a newborn patient who presented with chronic diarrhoea and failure to thrive diagnosed as cow’s milk protein enteropathy. The duodenal biopsy revealed granulamatous duodenitis which has not been described before. Her clinical and pathological findings responded well to cow’s milk elimination. We suggest that food allergies should be considered in differential diagnosis of patients with chronic diarrhoea and failure to thrive.

Experience of Post-Transplant Lymphoproliferative Disorder (PTLD) After Pediatric Liver Transplant: Incidence, Outcomes and Association with Food Allergy

Introduction We evaluated our 16 years of experience of pediatric PTLD cases who were liver transplanted in Başkent University Hospital between 2001-2017 years. Materials and Methods We reviewed the clinical and laboratory data of 8 patients who were diagnosed as PTLD out of 236 pediatric patients who were liver transplanted in Başkent University Hospital between 2001-2017 years. Pretransplant EBV statuses of 172 patients were also recorded. Results The total PTLD incidence was 3.4%. The incidence of PTLD was 10% in pretransplant EBV IgG negative patients, while it was 0.8% in pretransplant EBV seropositive patients. Mean age of the patients at liver transplant was 2.71±3.21 years; four patients were under 1 year of age at the time of transplant. PTLD was diagnosed 21.81±18.1 months after transplant. The primary site of involvement was variable among patients: peripheral and mediastinal lymph nodes, stomach-intestinal, transplanted graft, bone marrow, and nasopharynx. Eosinophil count varied greatly among patients, with mean values of 524.62±679. Food allergy prevalence was higher than the non-PTLD patients (23/236; 10% versus 3/8; 37.5%) The lymphoproliferative disease was of B cell origin in 6 of the patients. One patient died due to neutropenic sepsis during chemotherapy, while seven patients are being followed up in full remission for 7.75±4 years. Conclusion PTLD is a life-threatening complication of solid organ transplantation with a heterogenous clinic. Food allergy had a close association with PTLD. Close follow-up of patients who had risk factors and early diagnosis with appropriate treatment may lead to good outcome.

A single-center experience of post-transplant lymphoproliferative disorder (PTLD) cases after pediatric liver transplantation: Incidence, outcomes, and association with food allergy

BACKGROUND/AIMS We evaluated our 16-year single-center experience of pediatric post-transplant lymphoproliferative disorder (PTLD) cases who underwent liver transplantation between 2001 and 2017. MATERIALS AND METHODS Of the 236 pediatric patients who underwent liver transplantation between 2001 and 2017, the clinical and laboratory data of eight patients diagnosed with PTLD were reviewed. The pre-transplant Epstein-Barr virus (EBV) status of 172 patients was also recorded. RESULTS The total incidence of PTLD was 3.4%. The incidence of PTLD was 10% in pre-transplant EBV immunoglobulin G (IgG)-seronegative patients and 0.8% in pre-transplant EBV IgG-seropositive patients. The mean age of the patients at liver transplantation was 2.71±3.21 years, and four patients were aged below 1 year at the time of transplantation. PTLD was diagnosed at 21.81±18.1 months after transplantation. The primary site of involvement was variable among patients: peripheral and mediastinal lymph nodes, stomach and intestine, transplanted graft, bone marrow, and nasopharynx. The eosinophil count varied greatly among patients, with a mean value of 524.62±679/mm3. Three patients had a food allergy and were administered an elimination diet at the time of PTLD diagnosis. Six patients had PTLD of B-cell origin. One patient died due to neutropenic sepsis during chemotherapy, whereas seven patients were followed up in full remission for 7.75±4 years. CONCLUSION PTLD is a life-threatening complication of solid-organ transplantation with a heterogeneous clinical spectrum. Food allergy had a close association with PTLD. A close follow-up of patients with risk factors and an early diagnosis with appropriate treatment may lead to a better outcome.

Thrombin lag time is increased in children with mild asthma

BACKGROUND Inflammation and coagulation are closely linked events. Thrombin is the key enzyme in coagulation system and also has roles in inflammation. OBJECTIVE The aim of our study was to evaluate thrombin generation in children with mild asthma. METHODS Forty-two children with mild asthma and 49 healthy children were included in the study. All patients performed spirometry. Thrombin generation tests (TGT) were performed with a calibrated automated thrombogram (CAT) in children without asthma exacerbation during the last six months. During CAT assay thrombogram curves were obtained. The area under the curve showed endogenous thrombin potentials and indicated the total amount of endogenous thrombin generated; the peak height showed the highest thrombin value, thrombin lag time and time to thrombin peak were measured. RESULTS Thrombin lag time was significantly longer in children with asthma (3.98±1.2min) compared to those in the control group (3.29±0.6min) (p<0.01). Children with asthma also had longer thrombin tail time compared to the control group (19.5±8.9min vs. 16.7±2.9min, p=0.02). Thrombin peak was inversely correlated with FEF 25-75 (r=-0.41, p<0.01). Thrombin lag time was inversely correlated with FEF 25-75 (r=-0.39, p<0.01). CONCLUSION Inflammation in mild asthma seems to disturb coagulation but this disturbance may not be so strong as to increase thrombin levels and may only affect the initiation phase of thrombin generation.