Background Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult. Objective To assess the effect of supplementation of an infant ...and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life. Methods Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Results A total of 414 infants were randomized to the prebiotic group and 416 infants to the control group. A total of 300 infants were followed in the breast-feeding group. Up to the first birthday, atopic dermatitis occurred in significantly fewer infants from the prebiotic group (5.7%) than from the control group (9.7%; P = .04). The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group (7.3%). In a Cox regression model, the rate of atopic dermatitis was significantly lower by 44% in the prebiotic group versus the control group ( P = .04). The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants. Conclusion Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.
Background Lower prevalence of atopy was found in children with continuous exposure to livestock and thus to microbial compounds. In animal models exposure to endotoxin (LPS) decreases allergic ...sensitization and airway inflammation. Objective We sought to evaluate the effect of orally applied bacterial lysate in infancy on the prevalence of atopic dermatitis (AD) after the treatment phase at 7 months of age. Methods This randomized, placebo-controlled trial included 606 newborns with at least single heredity for atopy. From week 5 until the end of month 7, infants were treated orally with bacterial lysate containing heat-killed gram-negative Escherichia coli Symbio and gram-positive Enterococcus faecalis Symbio or its placebo. Children were followed until 3 years of age. Results There was no difference in the primary outcome between the active and placebo groups in the total study group. AD prevalence was significantly reduced at the end of the intervention phase (31 weeks of age) in the subgroup of infants with single heredity for atopy (relative risk, 0.52; 95% CI, 0.3-0.9). Ten percent (15/154) of infants in the active group had AD compared with 19% (27/145, P = .030) in the placebo group. This was more pronounced in the group of infants with paternal heredity for atopy (11% vs 32%, P = .004; relative risk, 0.34; 95% CI, 0.2-0.7). Conclusion Feeding of bacterial lysate might have prevented the development of AD, especially in children with paternal atopy, possibly indicating a preventive property only in subjects with a limited risk for atopy.
...supplementation of OS has been limited to the first year of life in these trials.4,5,8,9,E5 Whether supraphysiologic duration of OS supplementation would have an allergy-preventive effect ...persisting beyond the first year is an interesting research question that has not been adequately studied yet. ...there are indications that supplementation of infant diet in the first year of life with the immunoactive prebiotics tested here may have preventive potential against early AD, but the effect is not sustained in low-atopy-risk strata.
Background Randomized trials provide evidence to inform treatment decisions. The Consolidated Standards of Reporting Trials (CONSORT) Statement is a set of recommendations for the reporting of ...trials. Objective We sought to assess the quality of reporting allergen-specific immunotherapy trials according to CONSORT criteria. Methods The reporting of the procedure, randomization, dropouts, strict conduct of intention-to-treat (ITT) analysis, and sample size calculation according to CONSORT were assessed in the 46 subcutaneous and 48 sublingual immunotherapy (SLIT) blind, placebo-controlled randomized trials published between 1996 and 2009 in English. Results One subcutaneous immunotherapy (2.2%) and 3 SLIT (6.6%) trials met CONSORT Statement criteria. These were used for the registration of sublingual tablets to the European Medicines Agency. In subcutaneous immunotherapy, 16 (35%) studies reported a CONSORT flow chart, and 12 (26%) provided a description of dropouts. Adequate randomization was reported in 9 (35%) studies, and incomplete randomization was reported in 15 (33%). Power analysis was reported in 15 (33%) studies. In SLIT, 20 (42%) studies reported a CONSORT flow chart, and 16 (32%) a description of dropouts. ITT analysis was carried out in 1 (2.2%) SLIT study, and a modified ITT analysis was used in 1 (2.2%) subcutaneous immunotherapy study and 2 (4.4%) SLIT studies. Adequate randomization was reported in 6 (12%) studies, and incomplete randomization was reported in 16 (32%). Power analysis was reported in 15 (27%) studies. Conclusion As in other areas of medicine, the quality of reporting of most immunotherapy trials is low, and only 4.2% of SLIT randomized controlled trials met all of the criteria of the CONSORT Statement. Use of the CONSORT criteria should be encouraged.
...Di Bona et al1 performed a rigorous meta-analysis but overinterpreted the results while losing sight of other important parameters. ...the availability of AIT as a treatment option is an important ...part of evidence-based medicine and the patient-physician dialog.
Background The causal link between body mass index (BMI) or obesity and asthma in children is still being debated. Analyses of large longitudinal studies with a sufficient number of incident cases ...and in which the time-dependent processes of both excess weight and asthma development can be validly analyzed are lacking. Objective We sought to investigate whether the course of BMI predicts incident asthma in childhood. Methods Data from 12,050 subjects of 8 European birth cohorts on asthma and allergies were combined. BMI and doctor-diagnosed asthma were modeled during the first 6 years of life with latent growth mixture modeling and discrete time hazard models. Subpopulations of children were identified with similar standardized BMI trajectories according to age- and sex-specific “World Health Organization (WHO) child growth standards” and “WHO growth standards for school aged children and adolescents” for children up to age 5 years and older than 5 years, respectively (BMI-SDS). These types of growth profiles were analyzed as predictors for incident asthma. Results Children with a rapid BMI-SDS gain in the first 2 years of life had a higher risk for incident asthma up to age 6 years than children with a less pronounced weight gain slope in early childhood. The hazard ratio was 1.3 (95% CI, 1.1-1.5) after adjustment for birth weight, weight-for-length at birth, gestational age, sex, maternal smoking in pregnancy, breast-feeding, and family history of asthma or allergies. A rapid BMI gain at 2 to 6 years of age in addition to rapid gain in the first 2 years of life did not significantly enhance the risk of asthma. Conclusion Rapid growth in BMI during the first 2 years of life increases the risk of asthma up to age 6 years.
Background Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. Objective We ...sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Methods Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. Results The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. Conclusions LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.
Background IgE sensitization against grass pollen is a cause of seasonal allergic rhinitis. Objective We sought to investigate the evolution at the molecular level and the preclinical predictive ...value of IgE responses against grass pollen. Methods The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was administered yearly, and blood samples were collected at 1, 2, 3, 5, 6, 7, 10, and 13 years of age. Grass pollen–related seasonal allergic rhinitis (SARg) was diagnosed according to nasal symptoms in June/July. Serum IgE antibodies to Phleum pratense extract and 8 P pratense molecules were tested with immune-enzymatic singleplex and multiplex assays, respectively. Results One hundred seventy-seven of the 820 examined children had SARg. A weak monomolecular/oligomolecular IgE response to P pratense was observed very frequently before SARg onset. These initial IgE responses increased in concentration and molecular complexity during the preclinical and clinical process. A typical progression of IgE sensitization was observed: Phl p 1 (initiator in >75% of cases); then Phl p 4 and Phl p 5; then Phl p 2, Phl p 6, and Phl p 11; and then Phl p 12 and Phl p 7. At age 3 years, IgE sensitization predicted SARg by age 12 years (positive predictive value, 68% 95% CI, 50% to 82%; negative predictive value, 84% 95% CI, 80% to 87%). At this preclinical prediction time, the number of recognized molecules and the serum levels of IgE to P pratense were significantly lower than at 3 or more years after SARg onset. Conclusions The IgE response against grass pollen molecules can start years before disease onset as a weak monosensitization or oligosensitization phenomenon. It can increase in serum concentration and complexity through a “molecular spreading” process during preclinical and early clinical disease stages. Testing IgE sensitization at a preclinical stage facilitates prediction of seasonal allergic rhinitis at its molecular monosensitization or oligosensitization stage.
Background The only treatment option for peanut allergy is strict avoidance. Objective To investigate efficacy and safety of oral immunotherapy (OIT) in peanut allergy. Methods Twenty-three children ...(age, 3.2-14.3 years) with IgE-mediated peanut allergy confirmed by positive double-blind, placebo-controlled food challenge (DBPCFC) received OIT following a rush protocol with roasted peanut for 7 days. If a protective dose of at least 0.5 g peanut was not achieved, patients continued with a long-term buildup protocol using biweekly dose increases up to at least 0.5 g peanut. A maintenance phase for 8 weeks was followed by 2 weeks of peanut avoidance and a final DBPCFC. Immunologic parameters were determined. Results After OIT using the rush protocol, patients tolerated a median dose of only 0.15 g peanut. Twenty-two of 23 patients continued with the long-term protocol. After a median of 7 months, 14 patients reached the protective dose. At the final DBPCFC, patients tolerated a median of 1 g (range, 0.25-4 g) in comparison with 0.19 g peanut at the DBPCFC before OIT (range, 0.02-1 g). In 2.6% of 6137 total daily doses, mild to moderate side effects were observed; in 1.3%, symptoms of pulmonary obstruction were detected. OIT was discontinued in 4 of 22 patients because of adverse events. There was a significant increase in peanut-specific serum IgG4 and a decrease in peanut-specific IL-5, IL-4, and IL-2 production by PBMCs after OIT. Conclusion Long-term OIT appears to be safe and of some benefit in many patients with peanut allergy. With an increase in threshold levels and a reduction of peanut-specific TH 2 cytokine production, the induction of tolerance may be feasible in some patients.
Background The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. Objectives We sought to characterize the evolutionary patterns of ...the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. Methods We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust. Results One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kUA /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. Conclusions Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma.
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