Efficacy, Safety, and Quality of Life in a Multicenter, Randomized, Placebo-Controlled Trial of Low-Dose Peanut Oral Immunotherapy in Children with Peanut Allergy.

BACKGROUND: Only 2 small placebo-controlled trials on peanut oral immunotherapy (OIT) have been published. OBJECTIVE: We examined the efficacy, safety, immunologic parameters, quality of life (QOL), and burden of treatment (BOT) of low-dose peanut OIT in a multicenter, double-blind, randomized placebo-controlled trial. METHODS: A total of 62 children aged 3 to 17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo. The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge (OFC) after 16 months of OIT. We measured the occurrence of adverse events (AEs), immunologic changes, and QOL before and after OIT and BOT during OIT. RESULTS: Twenty-three of 31 (74.2%) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 (16.1%) in the placebo group (P < .001). Thirteen of 31 (41.9%) children of the active versus 1 of 31 (3.2%) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC (P < .001). There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number, severity, and treatment of objective AEs. In the peanut-OIT group, we noted a significant reduction in peanut-specific IL-4, IL-5, IL-10, and IL-2 production by PBMCs compared with the placebo group, as well as a significant increase in peanut-specific IgG4 levels and a significant improvement in QOL; 86% of children evaluated the BOT positively. DISCUSSION: Low-dose OIT is a promising, effective, and safe treatment option for peanut-allergic children, leading to improvement in QOL, a low BOT, and immunologic changes showing tolerance development.

Modified oral food challenge used with sensitization biomarkers provides more real-life clinical thresholds for peanut allergy.

BACKGROUND: Threshold levels for peanut allergy determined by using oral challenges are important for the food industry with regard to allergen labeling. Moreover, the utility of biological markers in predicting threshold levels is uncertain. OBJECTIVE: We sought to use a modified oral food challenge regimen that might determine threshold levels for peanut allergy mimicking a more real-life exposure and to correlate the eliciting dose (ED) and severity of clinical reaction in children with peanut allergy with B-cell, T-cell, and effector cell markers. METHODS: A modified food challenge procedure with doses scheduled 2 hours apart was used in 63 children with peanut allergy. All children received a maximum of 8 semi-log increasing titration steps of roasted peanuts ranging from 3 to 4500 mg of peanut protein until objective allergic reactions occurred. Severity of symptoms was graded from I to V. Biological markers were measured before challenge. RESULTS: Forty-five of 63 patients showed objective symptoms after greater than 30 minutes, with a median latency of clinical reaction of 55 minutes. By using a log-normal dose-distribution model, the ED5 was calculated to be 1.95 mg of peanut protein. The ED was significantly and inversely correlated with peanut- and Ara h 2-specific IgE levels, skin prick test responses, basophil activation, and TH2 cytokine production by PBMCs. Symptom severity did not correlate with any of the markers or the ED. CONCLUSION: This modified food challenge procedure might better reflect threshold levels for peanut allergy than the standard procedure because most of the patients reacted at a time interval of greater than 30 minutes. By using this model, threshold levels, but not severity, could be correlated with biological markers.

Lumbar disc herniation in three patients with cystic fibrosis: a case series.

INTRODUCTION: To date, lumbar disc herniation has not been reported in the context of cystic fibrosis even though back pain and musculoskeletal problems are very common in patients with cystic fibrosis. CASE PRESENTATION: We report on three patients with cystic fibrosis who experienced lumbar disc herniation in the course of their disease at ages 19 to 21 years (a 22-year-old Caucasian man, a 23-year-old Caucasian man, and a 21-year-old Caucasian woman). Our third patient eventually died because of her deteriorated pulmonary situation, which was influenced by the lumbar disc herniation as it was not possible for her to perform pulmonary drainage techniques properly because of the pain. CONCLUSIONS: Lumbar disc herniation can lead to a vicious cycle for patients with cystic fibrosis as it may promote pulmonary infections. This report highlights the need to investigate patients correctly.

Effect of breast-feeding on the development of atopic dermatitis during the first 3 years of life--results from the GINI-birth cohort study.

OBJECTIVE: To investigate if exclusive breast-feeding for 4 months is associated with atopic dermatitis during the first 3 years of life. STUDY DESIGN: Data on 3903 children were taken from yearly parental-administered questionnaires from a birth cohort study in Germany (recruited 1995-1998) comprised of a noninterventional (NI) and an interventional (I) subgroup. Outcomes were physician-diagnosed atopic dermatitis (AD) and itchy rash. Multiple logistic regression was performed for the entire cohort and stratified by family history of allergy and by study group adjusting for a fixed set of risk factors for allergies. RESULTS: Exclusive breast-feeding (52 % of children) was not associated with higher risk for AD either in the entire cohort (OR(adj,) 0.95; 95% CI, 0.79-1.14) or if stratified by family history of AD. In the I subgroup, but not in the NI subgroup, exclusive breast-feeding showed a significant protective effect on AD if compared with conventional cow's milk formula (OR(adj), 0.64; 95% CI, 0.45-0.90). CONCLUSION: These findings do not support the hypothesis that exclusive breast-feeding is a risk factor for development of atopic dermatitis but is protective if compared with conventional cow's milk. Observational studies might not be able to effectively control for selection bias and reverse causation.

Effect of exclusive breast-feeding and early solid food avoidance on the incidence of atopic dermatitis in high-risk infants at 1 year of age.

The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on atopic dermatitis (AD) in infancy. This study is part of a dietary clinical trial in a prospective cohort of healthy term newborns at risk of atopy. It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period. Eight hundred and sixty-five infants exclusively breast-fed, and 256 infants partially or exclusively formula-fed, were followed-up until the end of the first year following birth. AD and sensitization to milk and egg were considered as study end-points. The 1-year incidence of AD was compared between the two study groups. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given. In the breast-fed group, the adjusted OR for AD was 0.47 (95% CI 0.30-0.74). The strongest risk factor was the occurrence of AD in the subject's core family. The risk of infants with AD to be sensitized to milk was four times higher, and to egg eight times higher, than in infants without AD. Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence. We conclude that in infants at atopic risk, exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life.