Serum sRAGE levels in children with atopic dermatitis: a prospective study.

Introduction: Atopic dermatitis (AD) is chronic inflammatory skin disorder. The receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE. Aim: To determine serum sRAGE levels in children with AD. Material and methods: AD diagnosis was made according to Hanifin and Rajka criteria. Disease severity was scored by the scoring atopic dermatitis (SCORAD) index. Skin prick testing (SPT), total immunoglobulin E (Ig E) and eosinophil counts were analysed. The sRAGE levels were determined using ELISA technique. Results: The children, aged 0.4 to 2.0 years with AD (n = 65) were investigated in two groups according to the presence (AD+/Atopy+ [n = 40]) or absence (AD+/Atopy- [n = 25]) of SPT positivity. The comparisons were made with a healthy control group matched for age and sex. The medians (interquartile range) of sRAGE levels in patient and control groups were 8.43 (1.04-18.37) and 14.09 (6.35-28.64), respectively (p < 0.001). The medians (interquartile range) of sRAGE levels in AD+/Atopy+, AD+/Atopy- and control groups were 8.5 (3.1-17.27), 7.75 (1.04-18.37) and 14.09 (6.35-28.64), respectively (p = 0.004). Correlation analysis failed to reach significance with the disease severity sRAGE levels, total IgE levels and eosinophil counts. Conclusions: To our knowledge, this is the first study investigating the association of sRAGE levels with AD and disease severity in childhood. Serum sRAGE levels are decreased in AD but not correlated with disease severity. sRAGE levels may be important in the AD disease process.

A Novel Intronic Mutation Reduces HAX1 Level and is Associated With Severe Congenital Neutropenia.

Severe congenital neutropenia (SCN) is a rare disease. Autosomal recessive forms of SCN are more frequent in countries where consanguineous marriages are common. In this report, we describe a 54-day-old female with neutropenia who presented with ecthyma gangrenosum. Clinical exome sequencing was used to identify the mutation. HAX1 messenger RNA and isoforms were examined by real-time quantitative and conventional polymerase chain reaction. Bone marrow aspiration was stained by hematoxylin and eosin. Granulocytes were tested for apoptosis upon H2O2 exposure. T-cell proliferation was tested by flow cytometry. Clinical exome sequencing revealed a novel homozygous acceptor splice site mutation in intron 3 of HAX1 (c.505-1G>C), which reduced both isoforms A and B of HAX1 messenger RNA. The Western blot studies showed a complete absence of HAX1 protein. The purified neutrophils from the patient showed increased apoptosis upon H2O2 exposure, whereas T-cell proliferative responses to various stimuli were intact. The patient was treated with combined antibiotics, filgrastim, and placed on antibiotics prophylaxis. To the best of our knowledge, our data provide the first experimental evidence for HAX1 deficiency because of a splice site mutation. Although 3 other splice site variants have been deposited in databases, functional studies were missing. This novel variant of HAX1 may explain the SCN and secondary infections in our patients.

Spirometry in children with asthma and/or allergic rhinitis: comparison of FEF25-75% with the standard measures.

BACKGROUND: Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%), a spirometric measure of small airways, may predict the presence of airway responsiveness both in asthmatics and in allergic rhinitis (AR). We aimed to search the correlation between FEF25-75% and standard measures of spirometry (forced expiratory volume in the first second [FEV1%] and FEV1/FVC [forced vital capacity]) in different clinical conditions, that is in children with asthma, in children with asthma and AR, in children with AR and in healthy children. METHODS: Children with asthma (N.=116), asthma plus AR (N.=25), AR (N.=75) and healthy controls (N.=52) were evaluated. Clinical examinations, spirometry and bronchodilation tests were performed. RESULTS: In asthmatics there was a strong correlation between FEF25-75% and FEV1% (r=0.596, P<0.001); and between FEF25-75% and FEV1/FVC (r=0.740, P<0.001). In AR patients correlation between FEF25-75% and FEV1% (r=0.367, P=0.001); and between FEF25-75% and FEV1/FVC (r=0.534, P<0.001) were less prominent compared to asthmatics but they were still significant and strong. In children with both AR and asthma correlation between FEF25-75% and FEV1% (r=0.633, P=0.001) and between FEF25-75% and FEV1/FVC (r=0.539, P=0.005) were again significant. Pre-test FEV1% and FEF25-75% in AR patients were lower than that of the control subjects. After the bronchodilation, percentage change in the FEV1 in AR patients were significantly higher than the control subjects (P=0.010). AR patients showed significant increases in FEV1%, (P<0.001), FEF25-75%, (P<0.001) and (P=0.001) after the bronchodilation test. Within the AR patients, only 12/75 (16.0%) showed bronchodilation with salbutamol. Among the ones with a FEF25-75% <65%, FEV1% was normal in 6/43 (14%) patients in asthmatics, and FEV1% was normal in 3/9 (33%) patients in asthma +AR patients. CONCLUSIONS: Besides the FEV1% and FEV1/FVC, the FEF25-75% may be a useful and early spirometric parameter to evaluate the children with asthma and or AR.

Increased plasma soluble human leukocyte antigen-G in persistent wheezy infants.

BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical major histocompatibility complex class I antigen characterized by limited polymorphism in its coding region, unique tissue expression pattern in physiologic conditions and immunomodulatory properties. Recently, the level of soluble (s)HLA-G was found to be higher in atopic asthma and allergic rhinitis, but this remains to be clarified in wheezy infants. The aim of the present study was therefore to investigate sHLA-G in wheezy infants. METHODS: The subjects consisted of infants with persistent wheezing and positive modified asthma predictive index (mAPI; n = 30; persistent group) and those with transient wheezing and negative mAPI (n = 17; transient group). sHLA-G was measured in plasma using enzyme-linked immunosorbent assay. Total immunoglobulin E (IgE) and eosinophil count were measured, and skin testing was performed with a battery of 13 antigens with appropriate positive and negative controls. RESULTS: sHLA-G was significantly higher in the persistent wheezing (positive mAPI) group compared with the transient wheezing (negative mAPI) group (P = 0.008). There was no significant difference in peripheral blood eosinophil count and total IgE between the groups. CONCLUSIONS: The increased sHLA-G in infants with persistent wheeze suggests that sHLA-G may be able to be used to distinguish persistent from transient wheeze. Further comprehensive studies are needed on this topic.

The plasma gelsolin levels in atopic dermatitis: Effect of atopy ad disease severity

BACKGROUND: Gelsolin is an actin-binding protein with several cellular functions including anti-apoptosis and is reported to have an anti-inflammatory effect. Apoptosis of keratinocytes has been implicated as a key mechanism of atopic dermatitis (AD). OBJECTIVE: We aimed to determine plasma gelsolin (pGSN) levels in children with atopic dermatitis (AD). METHOD: The diagnosis of AD was made according to Hanifin and Rajka criteria. The disease severity was scored by objective SCORAD index by the same allergist. Skin prick testing (SPT), total IgE levels, and eosinophil counts were analyzed. The pGSN levels were determined using ELISA technique. RESULTS: Children aged between 0.5 and 3.0 years were included in the study. The children with AD (AD; n = 84) were analyzed in two groups according to the presence (AD+/Atopy+; n = 54) or absence of SPT positivity (AD+/Atopy−; n = 30). The comparisons were made with a healthy control group matched for age and sex (n = 81). The median (interquartile range) of pGSN levels in AD+/A+, AD+/A− and control groups were 267 μg/ml (236-368), 293 (240-498) and 547 (361-695), respectively (p < 0.001). The difference between the control group and AD sub-groups remained significant after Bonferroni correction (p < 0.001). Correlation analysis failed to reach significance with the disease severity total IgE levels and eosinophil counts. CONCLUSION: This is the first study investigating the association of pGSN levels with AD and disease severity. pGSN levels decreased in AD. These findings suggest that gelsolin may have a role in the disease process in AD patients

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The plasma gelsolin levels in atopic dermatitis: Effect of atopy and disease severity.

BACKGROUND: Gelsolin is an actin-binding protein with several cellular functions including anti-apoptosis and is reported to have an anti-inflammatory effect. Apoptosis of keratinocytes has been implicated as a key mechanism of atopic dermatitis (AD). OBJECTIVE: We aimed to determine plasma gelsolin (pGSN) levels in children with atopic dermatitis (AD). METHOD: The diagnosis of AD was made according to Hanifin and Rajka criteria. The disease severity was scored by objective SCORAD index by the same allergist. Skin prick testing (SPT), total IgE levels, and eosinophil counts were analyzed. The pGSN levels were determined using ELISA technique. RESULTS: Children aged between 0.5 and 3.0 years were included in the study. The children with AD (AD; n=84) were analyzed in two groups according to the presence (AD+/Atopy+; n=54) or absence of SPT positivity (AD+/Atopy-; n=30). The comparisons were made with a healthy control group matched for age and sex (n=81). The median (interquartile range) of pGSN levels in AD+/A+, AD+/A- and control groups were 267µg/ml (236-368), 293 (240-498) and 547 (361-695), respectively (p<0.001). The difference between the control group and AD sub-groups remained significant after Bonferroni correction (p<0.001). Correlation analysis failed to reach significance with the disease severity total IgE levels and eosinophil counts. CONCLUSION: This is the first study investigating the association of pGSN levels with AD and disease severity. pGSN levels decreased in AD. These findings suggest that gelsolin may have a role in the disease process in AD patients.

Effect of montelukast on clinical score and cytokine levels of infants for clinically diagnosed acute bronchiolitis

BACKGROUND: Acute bronchiolitis comprises a major cause for morbidity in infants with viral infection which induces an immune inflammatory response that may produce long lasting harmful effects. Currently, there is no effective therapy for bronchiolitis. OBJECTIVE: Our aim was to investigate the efficacy of five-day montelukast therapy in acute bronchiolitis management. METHODS: The study included 50 infants with acute bronchiolitis. The infants with first episode of acute bronchiolitis were randomly assigned to receive daily montelukast dose of 4 mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8 and IFN-gamma levels were evaluated before and after treatment by ELISA method. In the present study, the primary outcome measure was change in clinical severity score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL-8, IFN-gamma levels. RESULTS: No significant differences was found in clinical severity score with five-day montelukast treatment (p > 0.05, Mann-Whitney U test). There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma levels between the groups (p > 0.05 Mann-Whitney U test). There was significant decrease in plasma IFN-gamma levels following five-day montelukast treatment (p = 0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8, IFN-gamma levels between the groups after five-day montelukast treatment (p > 0.05, Wilcoxon). There was significant increase in eotaxin levels after five-day montelukast treatment (p = 0.009, Wilcoxon). CONCLUSION: Our study showed that montelukast affected plasma IFN-gamma and eotaxin levels after five days of treatment. Further studies are needed to demonstrate effects of montelukast on chemokine levels in bronchiolitis

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Effect of montelukast on clinical score and cytokine levels of infants for clinically diagnosed acute bronchiolitis.

BACKGROUND: Acute bronchiolitis comprises a major cause for morbidity in infants with viral infection which induces an immune inflammatory response that may produce long lasting harmful effects. Currently, there is no effective therapy for bronchiolitis. OBJECTIVE: Our aim was to investigate the efficacy of five-day montelukast therapy in acute bronchiolitis management. METHODS: The study included 50 infants with acute bronchiolitis. The infants with first episode of acute bronchiolitis were randomly assigned to receive daily montelukast dose of 4mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8 and IFN-gamma levels were evaluated before and after treatment by ELISA method. In the present study, the primary outcome measure was change in clinical severity score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL-8, IFN-gamma levels. RESULTS: No significant differences was found in clinical severity score with five-day montelukast treatment (p>0.05, Mann-Whitney U test). There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma levels between the groups (p>0.05 Mann-Whitney U test). There was significant decrease in plasma IFN-gamma levels following five-day montelukast treatment (p=0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8, IFN-gamma levels between the groups after five-day montelukast treatment (p>0.05, Wilcoxon). There was significant increase in eotaxin levels after five-day montelukast treatment (p=0.009, Wilcoxon). CONCLUSION: Our study showed that montelukast affected plasma IFN-gamma and eotaxin levels after five days of treatment. Further studies are needed to demonstrate effects of montelukast on chemokine levels in bronchiolitis.

Is yoga training beneficial for exercise-induced bronchoconstriction?

BACKGROUND: Some studies have shown the beneficial effects of yoga for individuals with bronchial hyperreactivity with regard to (1) a reduction in the use of rescue medication, (2) an increase in exercise capacity, and (3) an improvement in lung function. Despite the fact that yoga is promising as a new treatment for pediatric patients, further studies are needed to assess the use of this training for asthma management. OBJECTIVE: This study was performed to assess the beneficial effects of yoga in exercise-induced bronchoconstriction (EIB) in children. DESIGN: The study was prospective, with no control group. Participants were randomly chosen among the new patients at the unit. SETTING: This study was conducted in the Erciyes University School of Medicine, Pediatric Allergy Unit, in Kayseri, Turkey. PARTICIPANTS: Two groups of asthmatic children aged 6-17 y were enrolled in the study: (1) children with positive responses to an exercise challenge (n = 10), and (2) those with negative responses (n = 10). INTERVENTION: Both groups attended 1-h sessions of yoga training 2 ×/wk for 3 mo. OUTCOME MEASURES: Researchers administered spirometric measurement to all children before and immediately after participating in an exercise challenge. This process was performed at baseline and at the study's end. Age, gender, IgE levels, eosinophil numbers, and spirometric measurement parameters including forced expiratory volume in 1 sec (FEV1), forced expiratory flow 25%-75% (FEF25%-75%), forced vital capacity (FVC), peak expiratory flow percentage (PEF%), and peak expiratory flow rate (PEFR) were compared using the Mann-Whitney U test and the Wilcoxon test. A P value < .05 was considered significant. RESULTS: At baseline, no significant differences were observed between the groups regarding demographics or pre-exercise spirometric measurements (P > .05, Mann-Whitney U test). Likewise, no significant differences in spirometric measurements existed between the groups regarding the change in responses to an exercise challenge after yoga training (P > .05, Wilcoxon test). For the exercise-response-positive group, the research team observed a significant improvement in maximum forced expiratory volume 1% (FEV1%) fall following the exercise challenge after yoga training (P > .05, Wilcoxon test). All exercise-response-positive asthmatics became exerciseresponse-negative asthmatics after yoga training. CONCLUSION: This study showed that training children in the practice of yoga had beneficial effects on EIB. It is the research team's opinion that yoga training can supplement drug therapy to achieve better control of asthma.

Decreased levels of lipoxin A4 and annexin A1 in wheezy infants.

OBJECTIVE: Wheezing is a common and challenging health issue in infancy and early childhood. Asthma diagnosis is frequent in patients with a history of recurrent wheezing. A relationship has been reported between asthma and anti-inflammatory mediators such as lipoxin A4 and annexin A1. However, this remains uncertain in wheezy infants. The aim of the present study was to determine lipoxin A4 and annexin A1 levels in wheezy infants. MATERIALS AND METHODS: Eighty-seven patients aged 6-36 months were included in this study. Demographic characteristics, clinical features, laboratory data, clinical diagnoses, and treatments, if present, were recorded. Patients were divided into 2 groups: patients with wheezing (n = 59) and healthy controls (n = 28). Blood samples were taken and lipoxin A4 and annexin A1 levels were evaluated by ELISA. RESULTS: Lipoxin A4 and annexin A1 levels were significantly lower in the wheezing group than in the control group (p < 0.05). A significant correlation was found between the serum total immunoglobulin E (IgE) level and the percentage and absolute number of eosinophils (p < 0.05). No significant correlation was found in terms of lipoxin A4 and annexin A1 levels, the serum total IgE level, and the percentage and absolute number of eosinophils among groups (p > 0.05). CONCLUSION: This is the first study to assess lipoxin A4 and annexin A1 levels in wheezy infants. The levels of lipoxin A4 and annexin A1 were found to be low in wheezy infants. We hope that these results will lead to novel therapeutic options for asthma in cases where an optimal treatment modality is lacking.

Gastric signet ring carcinoma in a patient with ataxia-telangiectasia: a case report and review of the literature.

Ataxia-telangiectasia (A-T) is an autosomal recessive primary immunodeficiency disease characterized by progressive cerebellar ataxia, telangiectasia, sinopulmoner recurrent infections, and cancer susceptibility. Individuals with A-T are known to be at increased risk of certain malignancies including leukemia, lymphoma, and breast and gastric cancer. We present an 18-year-old case of A-T with Hashimoto thyroiditis who admitted with complaints of nausea, vomiting, anorexia, and weight loss. An upper endoscopic biopsy revealed gastric signet ring cell carcinoma. To the best of our knowledge, we report the first case of signet ring cell carcinoma in the patient with A-T. Our experience with occurrence of Hashimoto thyroiditis and gastric signet ring cell carcinoma in the same case of A-T underlines that the clinicians handling A-T must be vigilant about both malignancy and autoimmune disorders.

The efficacy of Pelargonium sidoides in the treatment of upper respiratory tract infections in children with transient hypogammaglobulinemia of infancy.

Transient hypogammaglobulinemia of infancy (THI), defined as prolongation of physiological hypogammaglobulinemia normally seen between the initial 3rd and 6th months of life, is one of the most common immune deficiencies of childhood. Recurrent upper respiratory tract infections (URTI) are rather common in this group of patients, and generally, antibiotic treatment is the usual choice, although viruses involved in most cases. Pelargonium sidoides extract a herbal drug with known immunmodulator, antiviral and antibacterial effects. In this randomized, placebo controlled, prospective, monocentric pilot study, 14 of 28 patients with a diagnosed THI, were given Pelargonium sidoides, while 14 were given placebo during the period of URTI. Before and after the treatment period of one week, complete blood count, prothrombin time, activated prothromboplastin time, serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, total and direct bilirubin levels were measured. Mothers were asked to fill in a questionnaire for the recovery of the clinical symptoms during the treatment. The results were evaluated and compared in both group to assess the effect of Pelargonium sidoides. As a conclusion, the Pelargonium sidoides group showed increased appetite. The Pelargonium sidoides were found to beneficial for the nasal congestion, recovery of daily and nocturnal cough but not found be significant. Further studies with large number of participants are necessary to highlight the effect of Pelargonium sidoides in children with transient hypogammaglobulinemia of infancy.