Spezifische Immuntherapie im Kindesalter

Background

Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy are the two routes for administering allergen-specific immunotherapy for inhalative allergens.

Immunotherapy

The only route of administration for children with bee or wasp venom allergy is SCIT and it is also the primary route of administration for children with asthmatic complaints. Both SCIT and SLIT were shown to be effective in controlling symptoms and in reducing rescue medication in patients with allergic rhinoconjunctivitis sensitized to grass pollens. There is evidence from clinical trials that SLIT with specific grass pollen allergens administered as tablets (e.g. Grazax and Oralair) or drops (Infecto-SLIT forte) is effective and safe in children. A recently published meta-analysis compared both forms of administration and showed a trend toward favoring SCIT for symptom and medication scores. Moreover, local adverse events after SLIT, such as oral pruritus, burning sensation, lip or tongue swelling and gastrointestinal symptoms are pronounced during the first months of administration, which might reduce patient compliance and adherence to specific immunotherapy. Finally, SCIT but not SLIT showed a reduced risk of developing asthma and new sensitization during treatment and 7 years after discontinuation of therapy indicating long-term preventive effects of SCIT.

Conclusions

Although there is evidence of effectiveness of both SCIT and SLIT with grass pollen extracts in patients with allergic rhinoconjunctivitis, SCIT is the primary mode of administration in children. Further research is needed to establish the clinical effectiveness of SCIT versus SLIT in a head-to-head trial in children.     

Allergen specific sublingual immunotherapy in children with asthma and allergic rhinitis

Background

The incidence of asthma and allergic rhinitis (AR) is significantly increased, especially in younger children. Current treatment for children with asthma and allergic rhinitis include allergen avoidance, standard pharmacotherapy, and immunotherapy. Since standard pharmacotherapy is prescribed for symptoms, immunotherapy at present plays an important role in the treatment of allergic diseases. This article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and asthma.

Data sources

PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms "asthma", "allergic rhinitis", "children", and "immune therapy". Additional articles were identified by hand searching of the references in the initial search.

Results

Numerous studies have shown that sublingual application of allergen specific immunotherapy (SLIT) is an adequate, safe and efficient substitution to subcutaneous route of allergens administration (SCIT) in the treatment of IgE-mediated respiratory tract allergies in children. According to the literature, better clinical efficacy is connected with the duration of treatment and mono sensitized patients.

Conclusions

At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT. SLIT reduces the symptoms of allergic diseases and the use of medicaments, and improves the quality of life of children with the diseases.

     

Allergenspezifische Immuntherapie/Hyposensibilisierung

Immunologic desensitization

Hyposensitization/allergen-specific immunotherapy represents the only disease-modifying treatment of IgE-mediated allergic disorders. According to test results relevant allergens are administered in increasing doses by subcutaneous or sublingual route. The most promising results in allergen immunotherapy are obtained in subcutaneous hyposensitization in insect venom allergy, allergic rhinoconjunctivitis and mild persistent bronchial asthma.

Possible adverse effects and their treatment

To prevent adverse effects of allergen-specific immunotherapy it is important to identify patient-related risk factors having a negative impact on the tolerance to treatment; these risk factors include acute infectious diseases, current allergic symptoms and individually excessive dose of allergen. Monitoring the patient by trained personnel during the first 30 min after subcutaneous allergen administration is mandatory. Systemic allergic reactions are treated immediately according to the prevailing symptoms, including prompt administration of epinephrine for anaphylaxis.

Conclusion

Hyposensitization treatment provided by allergy-experienced medical staff is a safe and sustainable therapy.     

Sublingual Immunotherapy Decreases Expression of Interleukin-33 in Children with Allergic Rhinitis

Objectives

To identify the expression of IL-33 during SLIT (Sublingual immunotherapy) in AR (Allergic rhinitis) children.

Methods

Thirty children received house dust mite (HDM) allergen extract for SLIT and thirty children received placebo in this study. Serum and nasal lavage samples of cases and controls were collected at different time points during SLIT. Interleukin (IL)-33 and other cytokines were estimated in these samples by enzyme-linked immuno sorbent assay (ELISA). Peripheral blood mononuclear cells (PBMC) were prepared and stimulated with rhIL-33 (with or without other stimulators) at different time points during SLIT.

Results

The present results showed that both serum and nasal lavage of IL-33 levels decreased significantly after 12 mo treatment and this trend maintained at least until 24 mo. The decreased nasal IL-33 level was positively correlated to local Th2 cytokines and increased IL-10 expression at 2 y post SLIT treatment. In vitro experiments showed that IL-33 promotes IL-4 and IL-5 and inhibits IL-10 expression by peripheral blood mononuclear cells (PBMCs) in AR.

Conclusions

Decreased IL-33 expression during SLIT may contribute to low Th2 response and enhanced Regulatory T cell cytokines expression. Thus, IL-33 maybe an important predictor during SLIT.

     

Spezifische Immuntherapie (SIT, Hyposensibilisierung) im Kindesalter

Allergen-specific immunotherapy

Allergen-specific immunotherapy (SIT: specific immunotherapy, hyposensizitation) represents at present the single therapeutic entity for allergic disease, which reduces symptom burden and demonstrates disease-modifying effects.

Indications

In children with allergic rhinitis/rhinoconjunctivitis, allergic asthma, and systemic reactions to hymenoptera stings, SIT has proven efficacy. The use of SIT in children with atopic dermatitis and oral allergy syndrome is under discussion. Prerequisites for the initiation of SIT are the detection of IgE (immunoglobulin E) antibodies or evidence of sensitization with the skin prick test to clinically relevant allergens, the availability of allergen extracts with proven efficacy for the underlying allergic disease, and the impossibility of allergen avoidance.

Contraindications

Contraindications for SIT are partially or fully uncontrolled asthma [FEV₁ <?70?% (FEV₁: forced expiratory volume in 1 s)], severe acute autoimmune disorders, severe immunodeficencies, acute inflammatory syndromes, malignancies, treatment with β-blockers and ACE (angiotensin-converting enzyme) inhibitors and cardiovascular diseases with increased risk of adverse events during administration of epinephrine.     

Controversial role of pets in the development of atopy in children

Background

Exposure to environmental allergens originating from different sources has been implicated in the sensitization to the respective allergens and development of atopic diseases. Keeping domestic animals is associated with exposure to relevant allergens but there are controversial data whether this exposure promotes or protects from the development of atopy.

Data sources

We herein reviewed the literature regarding the available data for the exposure to pets (cats and/or dogs) and the development of atopy. For this purpose, we searched the PubMed database.

Results

This review attempts to answer the following questions that arise from the daily practice and the relevant studies, which are: a) is pet keeping associated with sensitization? b) is there an association between keeping pets and the development of asthma, allergic rhinitis and eczema, and, c) what is the underlying mechanism of any possible protective association? Despite the fact that several studies and meta-analyses have been conducted to explore the role of pets in the development of atopy, there are still conflicting pieces of evidence. It seems that there are different effects depending on the type of pets, the time and duration of exposure, and the genetic background of the individual.

Conclusion

Further appropriately designed birth cohort studies are needed to explore whether exposure to relevant allergens from pets promotes or protects from the development of atopy.     

Sensitization to food allergens in Iranian children with mild to moderate persistent asthma

Background

Asthma is the most common chronic respiratory disease in childhood. The clinical presentation of asthma may worsen after food allergen ingestion in sensitized patients. To avoid nonspecific dietary restrictions in children with asthma, laboratory-based advice about foods is potentially helpful. The purpose of this study was to determine food sensitization in children with asthma.

Methods

Seventy-nine children with mild to moderate persistent asthma were included in this study. Commercial food allergens including cow??s milk, egg white, almond, potato, and soybean were used in skin prick tests. Specific IgE to 20 common food allergens was also measured in serum.

Results

Twelve (15.2%) of the patients had a positive skin prick test to at least one of the five food extracts. Sensitization was detected by skin prick tests to cow??s milk and egg white (each 6.3%), almond (3.8%), potato (2.5%) and soybean (1.3%). Specific IgE levels ??0.35 kAU/L were detected in the serum of 47% of the children with asthma. The most common food allergens were cow??s milk (26.6%), hazelnuts (25.3%), wheat flour (15.2%) and egg white (12.6%). Patients with a history of at least one hospital admission due to asthma attack had a higher rate of sensitization to egg.

Conclusions

In our study, food sensitization was frequent in Iranian children with asthma. Although clinical food allergy could not be evaluated because food challenge tests were not used in our study, skin prick tests and serum-specific IgE to common food allergens might be helpful in identifying children with food sensitization.     

Praktische Durchführung der Hyposensibilisierung

Background

Hyposensitization is a particularly promising method in children and adolescents.

Prerequisites

Hyposensitization treatment in children and adolescents requires a physician who is not only skilled in treating allergic diseases in children and adolescents but is also specialized in the emergency treatment of systemic allergic reactions in this age group and is in possession of the required emergency equipment.

Informed consent

Before carrying out any treatment the patient and the parents must be informed of the options and limitations as well as possible side effects and how to deal with them.

Performance

The exact indications, selection of the correct therapeutic procedure (sublingual or subcutaneous) and therapy details as well as the warranty of appropriate compliance are essential for successful therapy. Subcutaneous hyposensitization with inhalative allergens in the form of a short-term therapy, a preseasonal and all year round therapy (perennial) is possible, whereby the latter probably shows the best long-term results. Most preparations for sublingual immunotherapy are administered daily and perennially and for high-dosage preparations the first dose must be given under medical supervision.

Problematic

The recommended duration of therapy for hyposensitization with inhalative allergens is 3-5 years which often leads to problems with compliance. This can be improved by the introduction of recall systems, well organized practice and adequate consultation and treatment for the possible occurrence of side effects.     

Einfluss von Lebensbedingungen und Verhaltensweisen auf die Entwicklung von Immunsystem und Allergien im Ost-West-Vergleich (LISA)

Background

The frequency of allergic diseases shortly after reunification differed between East- and West Germany.

Design

In this prospective birth cohort study, 3,097 newborns were recruited in Munich, Leipzig and the Rhineland in 1998. Questionnaires, house dust and volatile organic compound (VOC) analyses, as well as blood tests, allowed to associate lifestyle related factors with immune parameters and the onset of atopic diseases.

Results

The frequency of atopic eczema (AE) differed significantly between the study centers. Solid food introduction past the sixth month had no influence on the development of an AE. Exposure to high concentrations of endotoxin in house dust early in life might protect against the development of an allergic immune response whereas exposure to allergens and indoor air chemicals changed the immune reactivity in the direction of an increased atopic risk.

Conclusions

The LISA study will help to identify associations between different lifestyle related factors and parameters of the immune system and atopic diseases.     

Effect of probiotics on allergic rhinitis in Df, Dp or dust-sensitive children: A randomized double blind controlled trial

Objective

To study, we examined the effect of Lactobacillus salivarius on the clinical symptoms and medication use among children with established allergic rhinitis (AR).

Design

Double blind, randomized, controlled trial.

Setting

Hualien Tzu-Chi General Hospital.

Methods

Atopic children with current allergic rhinitis received 4 × 10⁹ colony forming units/g of Lactobacillus salivarius (n=99) or placebo (n=100) daily as a powder mixed with food or water for 12 weeks. The SCORing Allergic rhinitis index (specific symptoms scores [SSS] and symptom medication scores [SMS]), which measures the extent and severity of AR, was assessed in each subject at each of the visits — 2 weeks prior to treatment initiation (visit 0), at the beginning of the treatment (visit 1), then at 4 (visit 2), 8 (visit 3) and 12 weeks (visit 4) after starting treatment. The WBC, RBC, platelet and, eosinophil counts as well as the IgE antibody levels of the individuals were evaluated before and after 3 months of treatment.

Results

The major outcome, indicating the efficacy of Lactobacillus salivarius treatment, was the reduction in rhinitis symptoms and drug scores. No significant statistical differences were found between baseline or 12 weeks in the probiotic and placebo groups for any immunological or blood cell variables.

Conclusions

Our study demonstrates that Lactobacillus salivarius treatment reduces rhinitis symptoms and drug usage in children with allergic rhinitis.     

Association of allergic rhinitis and sinusitis with childhood asthma

Objective

To study the point prevalence of allergic rhinitis and sinusitis in childhood asthma and to examine the relationship among them.

Methods

In 250 children (age <13 y) with mild-to-moderte asthma, allergic rhinitis was diagnosed by clinical plus nasal eosinophilia criteria, and sinusitis was diagnosed clinically plus confirmation by computerized tomography scan.

Results

The point prevalence of allergic rhinitis was 13.6%, and of sinusitis was 2%. On multivariate analysis, allergic rhinitis, sinusitis, and family history were significantly associated with asthma severity.

Conclusions

Allergic rhinitis is common in childhood asthama, but sinusitis is rare.

     

Prevalence and risk factors for allergic bronchopulmonary aspergillosis in Indian children with cystic fibrosis

Objectives

Allergic bronchopulmonary aspergillosis (ABPA) is a common complication in patients with cystic fibrosis. This crosssectional study was planned to determine the prevalence and risk factors for ABPA in Indian children with cystic fibrosis.

Methods

Clinical evaluation, spirometry, chest radiograph, sputum, total IgE, specific IgE for Aspergillus fumigatus, IgG precipitins and skin prick tests were done in 33 CF patients.

Results

Prevalence of allergic bronchopulmonary aspergillosis was 18.2% (95% CI 6.9%–35.4%): allergic bronchopulmonary aspergillosis was higher in patients with low cystic fibrosis score, age >12 years, atopy, and eosinophilia.

Conclusion

Prevalence of ABPA is higher in Indian children with cystic fibrosis.     

Effect of carbamazepine therapy on homocysteine, vitamin B12 and folic acid levels in children with epilepsy

Objectives

To compare the levels of homocysteine, vitamin B12 and folic acid before and after 6 months of carbamazepine therapy and to correlate them with carbamazepine level at 6 months.

Design

Prospective comparative study.

Setting

Tertiary care centre in North India.

Participants

51 children (2–12 years of age) presenting with motor partial seizures.

Intervention

Carbamazepine (10–20 mg/μ/day) for 6 months.

Main outcome measure

Change in serum homocysteine, B₁₂, folic acid level.

Methods

Fasting venous samples were collected before carbamazepine therapy and after six months. Homocysteine was analyzed using homocysteine enzyme immunoassay. Vitamin B₁₂ and folic acid were estimated using electrochemiluminesence technique. Carbamazepine levels were measured at 6 months.

Results

Of the 51 children, 36 (males-21), were followed up and their data analyzed. Mean homocysteine level was 11.51±3.95 μmol/L at recruitment and 11.77±6.65 μmol/L at six months (P=0.785). At recruitment 6(16%) children had homocysteine level above 15 μmol/L which increased to 10(27%) at 6 months. Mean vitamin B₁₂ at recruitment was 292.1±111.2 pg/mL and 297.8±82.9 pg/mL at 6 months (P=0.764). Mean folic acid at recruitment was 9.98±3.45 ng/mL and 10.66±3.97 ng/mL at 6 months (P=0.358). There was no correlation between carbamazepine levels with homocysteine, vitamin B₁₂ and folic acid (P>0.05). There was no effect of age, sex or dietary pattern on homocysteine levels.

Conclusion

Hence 6 months of carbamazepine therapy did not cause significant change in serum levels of homocysteine, vitamin B₁₂ and folic acid.     

Fractional exhaled nitric oxide in children with acute exacerbation of asthma

Objective

To determine whether fractional exhaled nitric oxide (FENO) has a utility as a diagnostic or predictive maker in acute exacerbations of asthma in children.

Design

Analysis of data collected in a pediatric asthma cohort.

Setting

Pediatric Chest Clinic of a tertiary care hospital

Methods

A cohort of children with asthma was followed up every 3 months in addition to any acute exacerbation visits. Pulmonary function tests (PFT) and FENO were obtained at all visits. We compared the FENO values during acute exacerbations with those at baseline and those during the follow up.

Results

243 asthmatic children were enrolled from August 2009 to December 2011 [mean (SD) follow up — 434 (227) days]. FENO during acute exacerbations was not different from FENO during follow up; however, FENO was significantly higher than personal best FENO during follow up (P < 0.0001). FENO during acute exacerbation did not correlate with the severity of acute exacerbation (P=0.29). The receiver operating characteristics curve for FENO as a marker for acute exacerbation had an area under the curve of 0.59. Cut-off of 20 ppb had a poor sensitivity (44%) and specificity (68.7%) for acute exacerbation.

Conclusions

FENO levels during acute exacerbation increase from their personal best levels. However, no particular cut off could be identified that could help in either diagnosing acute exacerbation or predicting its severity.     

Breastfeeding and transmission of cytomegalovirus to preterm infants. Case report and kinetic of CMV-DNA in breast milk

Background

Obesity has been identified as a risk factor for higher prevalence of asthma and asthma-related symptoms in children. The objective of this study was to evaluate the relationship between the prevalence of asthma symptoms and obesity among school-age children in the city of Ahvaz, Iran.

Methods

A total of 903 children, 7 to 11 years of age, were enrolled in this study through cluster sampling. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to identify the children who were currently suffering from asthma. Height and weight were measured and body mass index (BMI) was calculated in kg/m². Overweight was defined as BMI greater than the age- and sex-specific 85th percentile, and obesity as BMI greater than the 95th percentile. We determined the relationship between obesity and asthma symptoms by chi-square tests.

Results

The prevalence of wheeze ever, current wheezing, obesity, and overweight was 21.56%, 8.7%, 6.87%, and 9.5%, respectively. The current prevalence of wheezing among obese and overweight children was 68.75% and 37%, respectively, and there was a statistical association between obesity and the prevalence of current wheezing (p < 0.001), night cough (p < 0.001), and exercise-induced wheezing (p = 0.009), but obesity and overweight were not associated with eczema and allergic rhinoconjunctivitis, so it seems that the pathophysiology of asthma in obese and overweight children is not related to allergy.

Conclusion

There is a strong association between asthma symptoms and both overweight and obesity in both sexes among school-age children.     

Association of T-helper cell cytokine level with age in patients with biliary atresia: a preliminary study

Background

The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in patients with BA.

Methods

Twenty-eight patients with BA were divided into three groups according to their age (<?2 months, 2–3 months, and?≥?3 months). All the patients underwent Kasai portoenterostomy. Blood samples were collected from the patients preoperatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1β, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-β1 and liver expression of IL-1β, IL-6, and TGF-β1.

Results

The serum levels of IL-1β, IL-12p70, IL-6, and IL-10 in patients aged?≥?3 months were significantly higher than those in patients aged?<?2 months. There were no significant age-related differences in the IL-1β, IL-6 and TGF-β1 expression levels in the liver tissue of patients with BA.

Conclusions

The serum levels of IL-1β, IL-6, IL-10 and IL-12p70 showed significant age-related differences in patients with BA. Interpretation of the role of cytokines in BA needs to take patient’s age into consideration.

     

Intellectual disability in Indian children: experience with a stratified approach for etiological diagnosis

Objective

To study the clinico-etiological profile of children with intellectual disability using an algorithmic approach.

Design

Cross-sectional study.

Setting

Tertiary care centre in Northern India.

Participants

Consecutive children aged 3 months to 12 years, presenting with intellectual disability, confirmed by Developmental Assessment Scale for Indian Infants, Binet Kulshreshtha Test and Vineland Social Maturity Scale.

Method

All children were assessed on an internally validated structured proforma. A targeted approach included thyroid function tests, Brainstem evoked response audiometry, electroencephalogram, neuroimaging and metabolic screen done as a pre-decided schema. Genetic tests included karyotyping, molecular studies for Fragile X, Multiplex Ligation Dependent Probe Amplification and Array Comparative Genomic Hybridisation.

Results

Data of 101 children (median age 22 months) was analyzed. The etiological yield was 82.1% with genetic causes being the most common (61.4%) followed by perinatal acquired (20.4%), CNS malformations (12%), external prenatal (3.6%), and postnatal acquired (2.4%). Mild delay was seen in 11.7%, moderate in 21.7%, severe in 30.6% and profound in 35.6%.

Conclusion

It is possible to ascertain the diagnosis in most of the cases of intellectual disability using a judicious and sequential battery of tests.     

Risk factors for scholastic backwardness in children

Aim

To identify the risk factors for scholastic backwardness in children.

Participants

Children in the 6–12 year age group attending regular schools and referred to the child guidance clinic for scholastic backwardness.

Setting

Tertiary care hospital in South India.

Methods

Participants were compared with an age-and sexmatched group of children with good academic performance, to ascertain risk factors for scholastic backwardness.

Results

There were 75 boys and 35 girls in the study group. Among them 30 (27%) children had mental retardation, 39 (36%) had borderline intelligence and 12 (11%) had microcephaly. Undernutrition was noted in 36 (33%) children and 31 (28%) had stunted growth. 28 (26%) children had a history of chronic medical problems like epilepsy, bronchial asthma and congenital heart diseases. Visual, hearing and speech defects were present in 6 (6%), 5 (5%) and 12 (11%) children, respectively. Statistically significant differences were noted in the educational level and employment status of parents of children with scholastic backwardness and those with good academic performance.

Conclusion

Social and family factors have a significant influence on the academic functioning of children.     

Aeroallergen sensitization in childhood asthmatics in Northern India

Abstract

To determine the prevalence of sensitization to common aeroallergens in asthmatic children and study the differences in characteristics of atopics and non atopics.

Design

Analysis of data from a prospective cohort study.

Setting

Pediatric Chest Clinic of tertiary care center in Northern India

Patients

Asthmatic children from 5–18 year of age.

Main outcome measures

Prevalence of sensitization to common aeroallergens.

Results

Skin prick testing (SPT) was performed on 180 children above 5 years of age, with a mean (SD) age of 111.4 (34.2) months. 100 children (55.6%) were sensitized to at least one aeroallergen, suggesting atopy; 68 (37.8%) were sensitized to more than one allergen. 36.7% children were sensitized to housefly antigen; 31.1% to rice grain dust, 18.3% to cockroach, and 7.8% to house dust mite antigens. Atopic children had significantly higher median FENO during follow up than nonatopic children (17.5 ppb vs 13 ppb, P=0.002). There was a positive correlation between age and the number of allergens that an individual was sensitized to (r= 0.21; P=0.0049).

Conclusions

More than half of asthmatic children in our cohort had sensitization to one or more aeroallergens suggesting atopy; sensitization was most commonly seen to housefly antigen and rice grain dust. Atopic children had significantly higher FENO measurements during follow up as compared to non-atopic children.