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      Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study

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          Abstract

          Background

          The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes. Determining its prevalence, along with identifying those factors associated with its development will help to assess its clinical importance within the national setting and also add to the debate on appropriate prevention strategies.

          Methods

          A population based birth cohort study conducted in Hampshire, UK as part of the EuroPrevall birth cohort study. 1140 infants were recruited with 823 being followed up until 2 years of age. Infants with suspected food reactions were assessed including specific IgE measurement and skin prick testing. Diagnosis of food hypersensitivity was by positive double-blind, placebo-controlled food challenge (DBPCFC) where symptoms up to 48 h after the end of the food challenge were considered indicative of a food hypersensitivity. Factors associated with food hypersensitivity and its two phenotypes of IgE-mediated and non-IgE-mediated disease were modelled in a multivariable logistic regression analysis.

          Results

          Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens’ egg 2.7 % (1.6–3.8); cows’ milk 2.4 % (1.4–3.5); peanut 0.7 % (0.1–1.3); soy 0.4 % (0.0–0.8); wheat 0.2 % (0.0–0.5) and 0.1 % (0.0–0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens’ egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows’ milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal consumption of probiotics during breastfeeding and age at first solid food introduction.

          Conclusions

          Just under half the infants with confirmed food hypersensitivity had no demonstrable IgE. In an exploratory analysis, risk factors for this phenotype of food hypersensitivity differed from those for IgE-mediated food allergy except for a healthy infant diet which was associated with less risk for both phenotypes.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13601-016-0089-8) contains supplementary material, which is available to authorized users.

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          Most cited references40

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          Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.

          Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.
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            Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial.

            The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system. Probiotics, live health-promoting microbes, might offer such stimulation. We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases. We randomized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery. Their infants received the same probiotics plus galacto-oligosaccharides (n = 461) or a placebo (n = 464) for 6 months. At 2 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, and allergic rhinitis) and IgE sensitization (positive skin prick test response or serum antigen-specific IgE level >0.7 kU/L). Fecal bacteria were analyzed during treatment and at age 2 years. Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated (atopic) diseases (odds ratio [OR], 0.71; 95% CI, 0.50-1.00; P = .052). Probiotic treatment reduced eczema (OR, 0.74; 95% CI, 0.55-0.98; P = .035) and atopic eczema (OR, 0.66; 95% CI, 0.46-0.95; P = .025). Lactobacilli and bifidobacteria more frequently (P < .001) colonized the guts of supplemented infants. Probiotic treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema. The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics. The prevention of atopic eczema in high-risk infants is possible by modulating the infant's gut microbiota with probiotics and prebiotics.
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              Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis

              Objective To investigate whether filaggrin gene defects, present in up to one in 10 western Europeans and North Americans, increase the risk of developing allergic sensitisation and allergic disorders. Design Systematic review and meta-analysis. Data sources Medline, Embase, ISI Science Citation Index, BIOSIS, ISI Web of Knowledge, UK National Research Register, clinical trials.gov, the Index to Theses and Digital dissertations, and grey literature using OpenSIGLE. Study selection Genetic epidemiological studies (family, case-control) of the association between filaggrin gene defects and allergic sensitisation or allergic disorders. Data extraction Atopic eczema or dermatitis, food allergy, asthma, allergic rhinitis, and anaphylaxis, along with relevant immunological variables relating to the risk of allergic sensitisation as assessed by either positive skin prick testing or increased levels of allergen specific IgE. Data synthesis 24 studies were included. The odds of developing allergic sensitisation was 1.91 (95% confidence interval 1.44 to 2.54) in the family studies and 1.57 (1.20 to 2.07) in the case-control studies. The odds of developing atopic eczema was 1.99 (1.72 to 2.31) in the family studies and 4.78 (3.31 to 6.92) in the case-control studies. Three studies investigated the association between filaggrin gene mutations and allergic rhinitis in people without atopic eczema: overall odds ratio 1.78 (1.16 to 2.73). The four studies that investigated the association between filaggrin gene mutations and allergic rhinitis in people with atopic eczema reported a significant association: pooled odds ratio from case-control studies 2.84 (2.08 to 3.88). An overall odds ratio for the association between filaggrin gene mutations and asthma in people with atopic eczema was 2.79 (1.77 to 4.41) in case-control studies and 2.30 (1.66 to 3.18) in family studies. None of the studies that investigated filaggrin gene mutations and asthma in people without atopic eczema reported a significant association; overall odds ratio was 1.30 (0.7 to 2.30) in the case-control studies. The funnel plots suggested that publication bias was unlikely to be an explanation for these findings. No studies investigated the association between filaggrin gene mutations and food allergy or anaphylaxis. Conclusions Filaggrin gene defects increase the risk of developing allergic sensitisation, atopic eczema, and allergic rhinitis. Evidence of the relation between filaggrin gene mutations and atopic eczema was strong, with people manifesting increased severity and persistence of disease. Filaggrin gene mutations also increased the risk of asthma in people with atopic eczema. Restoring skin barrier function in filaggrin deficient people in early life may help prevent the development of sensitisation and halt the development and progression of allergic disease.
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                Author and article information

                Contributors
                kecg@soton.ac.uk
                t.n.bryant@soton.ac.uk
                erinoliver686@hotmail.com
                jane.martin@uhs.nhs.uk
                thyme_programming@consultant.com
                terrikemp@talktalk.net
                clare.mills@manchester.ac.uk
                keith.foote@hhft.nhs.uk
                bmm@soton.ac.uk
                kirsten.beyer@charite.de
                g.c.roberts@soton.ac.uk
                Journal
                Clin Transl Allergy
                Clin Transl Allergy
                Clinical and Translational Allergy
                BioMed Central (London )
                2045-7022
                26 January 2016
                26 January 2016
                2015
                : 6
                : 1
                Affiliations
                [ ]Clinical and Experimental Sciences and Human Development in Health Academic Unit, Faculty of Medicine, University of Southampton, Mailpoint 803, Level F, South Academic Block, Southampton, SO16 6YD UK
                [ ]Department of Nutrition and Dietetics, Southampton Children’s Hospital, Southampton, SO16 6YD UK
                [ ]Primary Care and Population Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD UK
                [ ]NIHR Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD UK
                [ ]The Hampshire Hospitals Foundation Trust, Winchester, SO22 5DG UK
                [ ]Institute of Inflammation and Repair, Manchester Academic Health Science Centre, Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK
                [ ]Department of Paediatric Pneumology and Immunology, Charité University Medical Centre, Berlin, Germany
                [ ]NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD UK
                Author information
                http://orcid.org/0000-0003-3649-7963
                Article
                89
                10.1186/s13601-016-0089-8
                4727377
                26816616
                cb7b871f-991d-4f5e-b5a4-e50a9418fcc2
                © Grimshaw et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 July 2015
                : 7 December 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000354, Food Standards Agency (GB);
                Award ID: TO7046
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Immunology
                food hypersensitivity,food allergy,epidemiology,europrevall,incidence,risk factors,dietary pattern analysis,healthy eating

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