Metin Aydogan

Efficacy of long-term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mite-allergic children with asthma

Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific‐allergen immunotherapy, the efficacy of long‐term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel‐group, controlled study. Children with asthma aged 4–16 yr, sensitive to house dust mite (HDM) were followed up for a run‐in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom‐medication scores and lung function tests every 3 months, as well as skin‐prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within‐group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM‐allergic children with asthma.

Sublingual immunotherapy in children with allergic rhinoconjunctivitis mono-sensitized to house-dust-mites: a double-blind-placebo-controlled randomised trial.

BACKGROUND Although sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficient treatment in children with seasonal allergic rhinitis (AR), there is little evidence on the efficacy of SLIT with house-dust-mite (HDM) extract in children with isolated perennial AR. OBJECTIVES We sought to assess the clinical efficacy and safety of HDM-SLIT in children with isolated allergic rhinitis-conjunctivitis mono-sensitized to HDM without asthma symptoms. METHODS Twenty-two children (aged 5-10 years) with perennial AR and conjunctivitis symptoms mono-sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae were enrolled. During a 2 months run-in period, symptom and medication scores, lung functions, bronchial hyperreactivity, nasal provocation and skin prick tests were evaluated. Subjects were randomized to active or placebo using a double-blind method. A total of eighteen subjects were randomised to receive either active SLIT or placebo for 12 months. Daily symptom and medication scores, baseline lung functions, bronchial hyperreactivity, nasal provocation and skin prick tests were recorded and re-evaluated at the end of treatment. RESULTS After one year of treatment, no significant differences were detected in the between groups and within group comparisons based on total rhinitis symptom/medication scores (p > 0.05). Skin reactivity to Dermatophagoides pteronyssinus was significantly reduced in HDM-SLIT compared to placebo group (p = 0.018). A significant reduction in nasal sensitivity was observed in SLIT group after one year treatment when compared to baseline (p = 0.04). Total conjunctivitis symptoms were reduced significantly in both active and lacebo group at the end of treatment compared to baseline. The proportion of patients with non-specific bronchial hyperreactivity increased to almost 3-fold in placebo group compared to baseline. CONCLUSION HDM-SLIT was not superior to placebo in reducing isolated rhinoconjunctivitis symptoms within 12 months of treatment. However, HDM-SLIT has a modulating effect on allergen-specific nasal and skin reactivity in isolated perennial AR children. CLINICAL TRIAL REGISTRATION The trial was registered at Anzctr.org.au number, ACTRN12613000315718.

Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model

Background Chitin, a natural polysaccharide extracted from shrimp, is a potent T and B cell adjuvant when delivered in the form of chitin microparticles and can shift a polarized T‐helper type 2 (Th2) immune response towards a Th1 response.

Comparison of Der p1-specific antibody levels in children with allergic airway disease and healthy controls

Although children, with allergic airway disease, who are sensitized to house‐dust mite (HDM) are known to have increased levels of allergen‐specific IgE and IgG, the association between the quantity of those immunoglobulins and the clinical features of disease is not yet well established. The purpose of this study was (i) to evaluate Der p1‐specific IgA, IgG1, IgG4, and IgE levels of children with HDM‐allergic asthma and allergic rhinitis and to compare it with that of healthy controls (ii) to assess the association with disease duration. A total of 73 patients were included. Of those, 58 had asthma (M/F: 27/31, mean age 7.9 ± 2.7 yr) and 15 were diagnosed as allergic rhinitis (M/F: 8/7, mean age 10.1 ± 4.0 yr) without asthma. Twenty‐five (M/F: 13/12, mean age 9.5 ± 4.2 yr) non‐allergic children were included as healthy controls. Data on age at onset and duration of disease were recorded. Then, Der p1‐specific IgA, IgG1, IgG4, IgE levels were measured in all of the 98 subjects by ELISA. Comparison of Der p1‐specific antibody levels of patients and controls revealed that Der p1‐specific IgG1, IgG4 and IgE levels of patients with asthma (p = 0.012, p = 0.021, p = 0.004, respectively) were significantly higher than healthy controls. Also, the ratio of Der p1‐specific IgA/IgE was significantly lower in asthmatic children when compared with children with allergic rhinitis and controls (p = 0.029, p < 0.001, respectively). Der p1‐specific IgG1, IgG4, IgE and IgA levels of asthmatic children with duration of disease of ≥4 yr were significantly higher than those with disease duration of <4 yr. IgA/IgE ratio was not significantly different in those two groups of asthmatics. We concluded that although all of the specific antibody levels increased with longer duration of asthma, IgA/IgE ratio remains to be low in asthmatic children allergic to HDM.

Neonatal BCG vaccination induces IL-10 production by CD4+ CD25+ T cells

Akkoc T, Aydogan M, Yildiz A, Karakoc‐Aydiner E, Eifan A, Keles S, Akin M, Kavuncuoglu S, Bahceciler NN, Barlan IB. Neonatal BCG vaccination induces IL‐10 production by CD4+ CD25+ T cells.
Pediatr Allergy Immunol 2010: 21: 1059–1063.
© 2010 John Wiley & Sons A/S

The predictive factors for remission of chronic spontaneous urticaria in childhood: Outcome from a prospective study

BACKGROUND There are few studies in children on the natural course of chronic spontaneous urticaria (CSU) because of its relative infrequency in childhood. OBJECTIVE To estimate the rate of remission and evaluate the prognostic factors in children with CSU. METHOD A total of 52 children with CSU were prospectively followed over a period of three years. RESULTS The remission rates at 12 months and 36 months were 32.7% and 48.1%. The mean duration of disease at the first visit in the non-remission group was higher than in the remission group at the end of the study (P=0.016). The remission rate of the patients who had been treated by standard dose antihistamine was higher than that of the patients who had been treated with the high-dose antihistamine and combination medications (P=0.004, P<0.001). The treatment steps were independent prognostic factors for remission by logistic regression analysis. CONCLUSION Our study indicates that urticaria controlled by a standard dose of antihistamine can predict a good prognosis independently from disease duration at first visit.

Membranous nephropathy in Schimke immuno-osseous dysplasia

Schimke immuno-osseous dysplasia is a rare autosomal recessive multi-system disorder, with clinical features of growth retardation, spondylo-epiphyseal dysplasia, nephrotic syndrome and immunodeficiency beginning in childhood. Here, we report a new case, in a 10-year-old boy with characteristic symptoms of Schimke immuno-osseous dysplasia. The patient presented with short stature and, later, developed nephrotic syndrome and peritonitis. In addition, he had perinuclear anti-neutrophilic cytoplasmic antibody (p-ANCA)-positive arthritis. Renal pathology of the patients with this disease usually show focal segmental glomerulonephritis, whereas our patient had membranous nephropathy, which has not previously been reported.

Transient peripheral leukocytosis in children with afebrile seizures.

The purpose of this study was (1) to demonstrate whether peripheral blood leukocytosis accompanies first afebrile seizures without bacterial infection, (2) to investigate the duration of leukocytosis, and (3) to assess the relationship between peripheral blood leukocytosis and seizure characteristics. Complete blood count was routinely obtained from all the patients. Blood and urine cultures were obtained from patients with leukocytosis. On the 24th hour of admission, a second complete blood count was obtained from patients with initial leukocytosis. Sixty-two children aged 4.0 ± 3.6 years (range, 6 months—13 years)—31 boys (50%) and 31 girls (50%)—enrolled in the study. The findings showed that peripheral blood leukocytosis was found in 8% of afebrile children without status epilepticus and 41.6% of afebrile children with status epilepticus. An interesting finding of the study was that peripheral blood leukocytosis accompanied by afebrile seizures subsided in 24 hours. Transient leukocytosis could be found in children with afebrile seizures without bacterial infection.

Long-term modulatory effect of Mycobacterium vaccae treatment on histopathologic changes in a murine model of asthma

BACKGROUND Mycobacteria are being investigated for modulation of inflammation in asthma and atopic disorders by eliciting particularly strong protective TH1 immune responses. OBJECTIVE To investigate the long-term effects of intratracheally administered Mycobacterium vaccae on an experimental murine model of asthma. METHODS BALB/c mice were placed in 4 groups: long-term M. vaccae, M. vaccae, asthma, and control groups. All groups but controls were sensitized intraperitoneally and challenged intratracheally with ovalbumin. The long-term M. vaccae and M. vaccae groups were treated with M. vaccae intratracheally simultaneously during challenges. Finally, mice in the long-term M. vaccae group were rechallenged with ovalbumin nebulization 24 days later. Evaluations of lung histopathologic findings and serum cytokine levels were performed. RESULTS Comparison of the long-term M. vaccae group with the asthma model group revealed that the number of hyperplasic goblet cells in small and large airways (small airway: P < .05; large airways: P < .01) and thickness of basement membrane in large airways were significantly less in the long-term M. vaccae group. Furthermore, numbers of hyperplasic goblet cells in small airways (P < .05) and basement membrane in the large airway (P < .05), as well as inflammation in small airways (P < .01), were significantly less in the M. vaccae group when compared with the asthma model group. Interferon-gamma secretion from splenocytes of the M. vaccae group was significantly higher than the asthma model and long-term M. vaccae groups. CONCLUSION Intratracheal administration of M. vaccae exerted a long-lasting ameliorating effect on airway histopathologic features of a murine asthma model.

Predicting Hospitalization in Children with Acute Asthma

BACKGROUND Acute asthma is one of the most common medical emergencies in children. Appropriate assessment/treatment and early identification of factors that predict hospitalization are critical for the effective utilization of emergency services. OBJECTIVE To identify risk factors that predict hospitalization and to compare the concordance of the Modified Pulmonary Index Score (MPIS) with the Global Initiative for Asthma (GINA) guideline criteria in terms of attack severity. METHODS The study population was composed of children aged 5-18 years who presented to the Emergency Departments (ED) of the tertiary reference centers of the country within a period of 3 months. Patients were evaluated at the initial presentation and the 1(st) and 4(th) hours. RESULTS Of the 304 patients (median age: 8.0 years [interquartile range: 6.5-9.7]), 51.3% and 19.4% required oral corticosteroids (OCS) and hospitalization, respectively. Attack severity and MPIS were found as predicting factors for hospitalization, but none of the demographic characteristics collected predicted OCS use or hospitalization. Hospitalization status at the 1(st) hour with moderate/severe attack severity showed a sensitivity of 44.1%, specificity of 82.9%, positive predictive value of 38.2%, and negative predictive value of 86.0%; for MPIS ≥ 5, these values were 42.4%, 85.3%, 41.0%, and 86.0%, respectively. Concordance in prediction of hospitalization between the MPIS and the GINA guideline was found to be moderate at the 1(st) hour (κ = 0.577). CONCLUSION Attack severity is a predictive factor for hospitalization in children with acute asthma. Determining attack severity with MPIS and a cut-off value ≥ 5 at the 1(st) hour may help physicians in EDs. Having fewer variables and the ability to calculate a numeric value with MPIS makes it an easy and useful tool in clinical practice.