[Severe atopy and allergy--rare hyper-IgE syndrome caused by the DOCK8 mutation as underlying condition]. / Taustalla harvinainen DOCK8-mutaation aiheuttama hyper-IgE-syndrooma. Vaikea atopia ja allergia.

The DOCK8 hyperimmunoglobulin E syndrome is an autosomal recessive primary combined immunological deficiency. Severe atopic eczema having its onset in infancy, food allergies, chronic viral infections of the skin, and recurrent pneumonias are central symptoms. Serum IgE level is high and eosinophilia is found in the blood. In addition, abnormalities in the number and function of lymphocytes can be detected. The disease may be difficult to distinguish from severe allergic eczema and asthma. The diagnosis is made through a gene test. We describe a 13-year-old boy, whose disease was cured with allogenic stem cell transplantation.

Childhood asthma management guided by repeated FeNO measurements: a meta-analysis.

The fraction of exhaled nitric oxide (FeNO) has gained interest as a non-invasive tool to measure airway inflammation in asthma since it reflects allergic inflammation. Recent controlled clinical studies have, however, questioned its role in the management of asthma in children. To assess the clinical value of FeNO in paediatric asthma management, a meta-analysis was performed on the controlled studies of childhood asthma management guided by repeated FeNO measurements, and relevant publications on the confounders of FeNO were reviewed. The data suggests that utilising FeNO to tailor the dose of inhaled corticosteroids in children cannot be recommended for routine clinical practice since there is a danger of excessive inhaled corticosteroid doses in children without meaningful changes in clinical outcomes. Many disease and non-disease related factors (most importantly atopy, height/age and infection) affect FeNO levels which can easily confound the interpretation.

Atopic characteristics of wheezing children and responses to prednisolone.

We wanted to test the hypothesis that the efficacy of systemic corticosteroid is associated with atopic characteristics in wheezing children. A randomized controlled trial comparing oral prednisolone (2 mg/kg/day in 3 divided doses for 3 days) with placebo in hospitalized wheezing children (n = 266, median 1.6 years, range 3 months to 15.2 years) was conducted. In this post-hoc analysis, we assessed the link between the efficacy of prednisolone and several atopic characteristics, such as atopy, aeroallergen sensitization, total IgE level, number of sensitizations, eczema, atopic eczema, blood or nasal eosinophils, exhaled nitric oxide, positive modified asthma predictive index/asthma, inhaled corticosteroid medication and parental asthma/allergy. Virology was studied comprehensively. Our primary endpoint was the time until ready for discharge, and the most important secondary endpoint was the occurrence of relapses during the following 2 months. For statistics, we used interaction analyses in uni- and multivariate regression models. Overall, prednisolone did not decrease any of our predefined clinical endpoints. Neither was the efficacy of prednisolone associated with atopy. However, prednisolone significantly decreased the time until ready for discharge in children with positive modified asthma predictive index/asthma, inhaled corticosteroids, or rhinovirus infection and/or in children without azithromycin treatment. Prednisolone significantly decreased relapses in children with eczema, nasal eosinophilia and rhinovirus infection. The multiple clinical, inflammatory and viral markers associating with the efficacy of prednisolone should be confirmed in prospective trials. It is important that corticosteroid intervention trials have strict design for these potentially confounding factors.

Evaluation of the efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus.

BACKGROUND: The role of systemic corticosteroids in the treatment of early childhood wheezing in children is not clear. OBJECTIVE: We sought to determine whether prednisolone is effective in rhinovirus-induced early wheezing. METHODS: We conducted a controlled trial comparing oral prednisolone (2 mg/kg per day in three divided doses for 3 days) with placebo in 78 hospitalized children (mean age, 1.1 year; standard deviation, 0.7) experiencing their first or second episode of wheezing induced by rhinovirus or respiratory syncytial virus. Mixed viral infections were excluded. Our primary end point was the time until the patient was ready for discharge; secondary end points included oxygen saturation during hospitalization, duration of symptoms, occurrence of relapses during the next 2 months and blood eosinophil counts at discharge and 2 weeks later. RESULTS: In multivariate regression analysis, prednisolone did not influence the time until ready for discharge, but it decreased relapses during the subsequent 2-month period in rhinovirus-affected children (prednisolone versus placebo, 22% versus 56%; odds ratio, 19.06; 95% confidence interval, 2.52-144.03; P = 0.004) and in children with blood eosinophils > or = 0.2 x 10/L (respectively, 24% versus 71%; odds ratio, 10.57; 95% confidence interval, 1.99-56.22; P = 0.006). Rhinovirus-affected children had more blood eosinophils on admission (mean, 0.44 versus 0.086 x 10/L), had a higher prevalence of atopy (44% versus 8%) and were older (mean, 1.4 versus 0.9 years, P < 0.001 for all) than respiratory syncytial virus-infected children. CONCLUSION: Prednisolone reduced relapses during a 2-month period after first episodes of wheezing associated with rhinovirus infection or blood eosinophils > or = 0.2 x 10/L.

A follow-up study of nutrient intake, nutritional status, and growth in infants with cow milk allergy fed either a soy formula or an extensively hydrolyzed whey formula.

BACKGROUND: Infants with cow milk allergy (CMA) are reported to have reduced growth and special nutritional needs. OBJECTIVE: The aim of the present study was to compare nutrient intake, nutritional status, and growth in infants with CMA who were fed either a soy formula or an extensively hydrolyzed whey formula. DESIGN: The study group comprised 168 double-blind challenge-proven infants with CMA. Eighty-four of the infants were fed a soy formula (mean starting age: 7.8 mo), and the other 84 infants were fed an extensively hydrolyzed whey formula (mean starting age: 7.5 mo). RESULTS: The length (SD score) of the infants was close to the mean Finnish reference growth by age 2 y in both groups. Weight-for-length measurements continued to reach the 50th percentile by age 4 y in both study groups. The mean nutrient intake followed the recommended intake in both groups, although most of the infants were supplemented with calcium and vitamin D. The observed serum transferrin receptor concentrations indicated a greater iron inadequacy in the tissue of infants in the soy formula group than in the hydrolyzed whey formula group (P = 0.08). However, there were no significant differences between the groups either in the percentages of abnormally low laboratory values (mean cell volume, hemoglobin, zinc, and ferritin) or in the percentages of high alkaline phosphatase activity, which indicates the comparable safety and effectiveness of the formulas studied. CONCLUSIONS: Both nutritional status and growth were well within reference values in the 2 groups, and the selection of a formula can largely be made on the basis of infant tolerance to the formulas.

The link between bronchiolitis and asthma.

Bronchiolitis and asthma are common wheezing illnesses of childhood. Respiratory syncytial virus is the main causative agent of Bronchiolitis. Rhinovirus is the most common trigger of exacerbations of asthma, but also has been detected increasingly in doing children with Bronchiolitis. Reportedly, childhood asthma develops in 40% of children with a history of Bronchiolitis. No convincing link has been reported between Bronchiolitis and development of atopy, although atopy generally is regarded as the main risk factor for chronic asthma. This article focuses on the association between bronchiolitis and the development of asthma. The authors address the question how respiratory syncytial virus and rhinovirus infections in young children, together with genetics and immunologic immaturity, may contribute to the development of asthma.

Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema.

BACKGROUND: Rhinovirus-induced early wheezing has been suggested as a new important risk factor for recurrent wheezing. OBJECTIVE: We sought to investigate the risk factors for recurrent wheezing and to determine post hoc the efficacy of prednisolone in risk groups. METHODS: We followed for 1 year 118 children (median age, 1.1 years) who had had their first episode of wheezing and had participated in a trial comparing prednisolone with placebo in hospitalized children. Demographics and laboratory data were obtained at study entry. The follow-up outcome was recurrent wheezing (3 physician-confirmed episodes). RESULTS: Recurrent wheezing was diagnosed in 44 (37%) children. Independent risk factors were age < 1 year, atopy, and maternal asthma. The probability of recurrent wheezing was higher in rhinovirus than respiratory syncytial virus (RSV)-affected children among placebo recipients (hazard ratio, 5.05; 95% CI, 1.00-25.41). Prednisolone decreased the probability of recurrent wheezing in children with eczema (0.15; 95% CI, 0.04-0.63) but not in those without eczema (1.89; 95% CI, 0.83-4.29; P = .007 for interaction). Prednisolone was associated with less recurrent wheezing in the rhinovirus group (0.19; 95% CI, 0.05-0.71), but not in the RSV (2.12; 95% CI, 0.46-9.76) or in the RSV/rhinovirus-negative groups (2.03; 95% CI, 0.83-5.00; P = .017 for interaction). CONCLUSION: Rhinovirus-induced early wheezing is a major viral risk factor for recurrent wheezing. Prednisolone may prevent recurrent wheezing in rhinovirus-affected first-time wheezers. The presence of eczema may also influence the response to prednisolone. CLINICAL IMPLICATIONS: A prospective trial is needed to test the hypothesis that prednisolone reduces recurrent wheezing in rhinovirus-affected wheezing children.

Efficacy of prednisolone in children hospitalized for recurrent wheezing.

Data on the efficacy of corticosteroids on respiratory picornavirus-induced wheezing are limited. To determine whether prednisolone is effective in rhinovirus- or enterovirus-induced recurrent wheezing, we conducted a controlled trial comparing oral prednisolone (2 mg/kg/day in three divided doses for 3 days) with placebo in hospitalized wheezing children and studied post hoc virus-specific efficacy in early wheezing (<3 episodes, reported elsewhere) and in recurrent wheezing (>or=3 episodes). Virus-negative children where excluded. Our primary endpoint was the time until children were ready for discharge. Secondary endpoints included oxygen saturation and exhaled nitric oxide during hospitalization, duration of symptoms, blood eosinophil count, and impulse oscillometry 2 wk after discharge, and occurrence of relapses during the following 2 months. Virus-specific effects were analyzed with interaction analysis in a multivariate regression model. During the study period, 661 patients were hospitalized, 293 randomized, and 59 were accepted in this analysis (mean age 2.6 yr, s.d. 1.3). Prednisolone did not significantly decrease the time until ready for discharge in all patients (prednisolone vs. placebo, medians, 18 vs. 24 h, p = 0.11). However, prednisolone decreased the time until ready for discharge in children with picornavirus infection (respectively, 12 vs. 24 h, p = 0.0022) and more specifically, in children with enterovirus infection (6 vs. 35 h, p = 0.0007). In the secondary endpoints, prednisolone decreased the duration of cough and dyspnea in rhinovirus-affected children (p = 0.033 for both). Prospectively designed clinical trial is needed to test the hypothesis that prednisolone reduces symptoms in picornavirus-affected wheezing children.

Feeding a soy formula to children with cow's milk allergy: the development of immunoglobulin E-mediated allergy to soy and peanuts.

Peanut allergy has been associated with the intake of soy milk or a soy formula. We studied the development of immunoglobulin E antibodies specific to soy and peanuts and of allergic reactions caused by peanuts, in children with confirmed cow's milk (CM) allergy fed either a soy formula or an extensively hydrolyzed formula (EHF). One hundred and seventy infants with documented CM allergy (CMA) were randomly assigned to receive either a soy formula or an EHF. The children were followed to the age of 4 yr. Peanut-specific immunoglobulin E was measured at the age of 4. A detailed history of the occurrence of allergic reactions caused by peanuts was recorded by the parents. Soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1, 2 and 4 yr. Immunoglobulin E antibodies to soy (> or =0.35 kU/l) were found in 22 of 70 children fed the soy formula, and in 14 of 70 of the children fed the EHF (p = 0.082). In an open challenge with soy at the age of 4, no immediate reactions were observed. One of 72 children from the soy group had a delayed reaction. immunoglobulin E antibodies to peanuts (> or =0.35 kU/l) were found in 21 of 70 children fed the soy formula and 17 of 69 infants fed the EHF (p = 0.717). The incidence of reported peanut allergy in the soy group was two of 72 (3%) and four of 76 (5%) in the EHF group (p = 0.68). Development of immunoglobulin E-associated allergy to soy and peanuts was rare in our study group of milk allergic children. The use of a soy formula during the first 2 yr of life did not increase the risk of development of peanut-specific immunoglobulin E antibodies or of clinical peanut allergy.

Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years.

OBJECTIVES: We conducted a prospective, randomized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow's milk allergy. STUDY DESIGN: Infants (n = 170) with documented cow's milk allergy were randomly assigned to receive either a soy formula or an extensively hydrolyzed formula. If it was suspected that the formula caused symptoms, a double-blind, placebo-controlled challenge (DBPCFC) with the formula was performed. The children were followed to the age of 2 years, and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years. RESULTS: An adverse reaction to the formula was confirmed by challenge in 8 patients (10%; 95% confidence interval, 4.4%-18.8%) randomly assigned to soy formula and in 2 patients (2.2%; 95% confidence interval, 0.3% to 7.8%) randomly assigned to extensively hydrolyzed formula. Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow's milk allergy (11% and 9%, respectively). IgE to soy was detected in only 2 infants with an adverse reaction to soy. Adverse reactions to soy formula were more common in younger (<6 months) than in older (6 to 12 months) infants (5 of 20 vs 3 of 60, respectively, P =.01). CONCLUSIONS: Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow's milk allergy. Development of IgE-associated allergy to soy was rare. Soy formula can be recommended as a first-choice alternative for infants >or=6 months of age with cow's milk allergy.

Prediction of the development of tolerance to milk in children with cow's milk hypersensitivity.

OBJECTIVES: To investigate whether the development of tolerance to cow's milk (CM) by aged 4 years can be predicted with a skin prick test (SPT) and measurements of total or specific immunoglobulin E (IgE) in the serum, taken at the time of diagnosis of cow's milk hypersensitivity (CMH). STUDY DESIGN: Infants with immediate (n=95) or delayed (n=67) challenge reactions to CM were prospectively followed to aged 4 years. CMH status was assessed annually by CM challenges. RESULTS: By aged 2, 3, and 4 years, children with delayed reactions developed tolerance to CM faster than those with immediate reactions: 64%, 92%, and 96% versus 31%, 53%, and 63%, respectively. A wheal size of <5 mm in SPT correctly identified 83% of 124 infants who developed tolerance to CM by aged 4 years, and a wheal size of >or=5 mm in SPT correctly identified 71% of 39 infants with persistent CMH. Milk-specific IgE <2 kU/L correctly identified 82% of infants who developed tolerance to CM, and milk-specific IgE >or=2 kU/L correctly identified 71% of infants with persistent CMH. CONCLUSION: SPT and milk-specific IgE in the serum are useful prognostic indicators of the development of tolerance to CM in infants with CMH.