Helen A. Brough

Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy

BACKGROUND The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy. METHODS We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test--one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age. RESULTS Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy. CONCLUSIONS The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.).

Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants

BACKGROUND The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy. METHODS We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cows milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standard-introduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age. RESULTS In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P=0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standard-introduction group (2.4% vs. 7.3%, P=0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P=0.003) and egg allergy (1.4% vs. 5.5%, P=0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe. CONCLUSIONS The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.).

Effect of Avoidance on Peanut Allergy after Early Peanut Consumption

BACKGROUND In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group). METHODS At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. RESULTS We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio. CONCLUSIONS Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.).

EAACI Molecular Allergology User's Guide

The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)‐mediated responses and enabled ‘component‐resolved diagnosis’ (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology Users Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low‐abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross‐reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE‐mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross‐reactive panallergens from plant (lipid transfer proteins, polcalcins, PR‐10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE‐mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.

Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy.

Background History and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy. Objective We sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk. Methods Peanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study. Results There was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01). Conclusion Exposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA.

Peanut allergy: Effect of environmental peanut exposure in children with filaggrin loss-of-function mutations

Background Filaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption. Objective We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds. Methods Exposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations. Results After adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 μg of peanut protein per gram (95% CI, 0.70-1.22 μg/g), that for CRD sensitization was 1.03 μg/g (95% CI, 0.90-1.82 μg/g), and that for peanut allergy was 1.17 μg/g (95% CI, 0.01-163.83 μg/g). Conclusion Early-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired skin barrier.

Peanut protein in household dust is related to household peanut consumption and is biologically active

BACKGROUND Peanut allergy is an important public health concern. To understand the pathogenesis of peanut allergy, we need to determine the route by which children become sensitized. A dose-response between household peanut consumption (HPC; used as an indirect marker of environmental peanut exposure) and the development of peanut allergy has been observed; however, environmental peanut exposure was not directly quantified. OBJECTIVE We sought to explore the relationship between reported HPC and peanut protein levels in an infants home environment and to determine the biological activity of environmental peanut. METHODS Peanut protein was quantified in wipe and dust samples collected from 45 homes with infants by using a polyclonal peanut ELISA. Environmental peanut protein levels were compared with peanut consumption assessed by using a validated peanut food frequency questionnaire and other clinical and household factors. Biological activity of peanut protein in dust was assessed with a basophil activation assay. RESULTS There was a positive correlation between peanut protein levels in the infants bed, crib rail, and play area and reported HPC over 1 and 6 months. On multivariate regression analysis, HPC was the most important variable associated with peanut protein levels in the infants bed sheet and play area. Dust samples containing high peanut protein levels induced dose-dependent activation of basophils in children with peanut allergy. CONCLUSIONS We have shown that an infants environmental exposure to peanut is most likely to be due to HPC. Peanut protein in dust is biologically active and should be assessed as a route of possible early peanut sensitization in infants.

Distribution of peanut protein in the home environment

BACKGROUND To halt the increase in peanut allergy, we must determine how children become sensitized to peanut. High household peanut consumption used as an indirect marker of environmental peanut exposure is associated with the development of peanut allergy. OBJECTIVE We sought to validate a method to quantify environmental peanut exposure, to determine how peanut is transferred into the environment after peanut consumption, and to determine whether environmental peanut persists despite cleaning. METHODS After initial comparative studies among 3 ELISA kits, we validated and used the Veratox polyclonal peanut ELISA to assess peanut protein concentrations in dust and air and on household surfaces, bedding, furnishings, hand wipes, and saliva. RESULTS The Veratox polyclonal peanut ELISA had the best rate of recovery of an independent peanut standard. We demonstrated 100% sensitivity and specificity and a less than 15% coefficient of variation for intra-assay, interassay, and interoperator variability. There was high within-home correlation for peanut protein levels in dust and household surface wipes. Airborne peanut levels were lower than the limit of quantitation for the Veratox polyclonal peanut ELISA in a number of simulated scenarios, except for a brief period directly above peanuts being deshelled. Peanut protein persisted on hands and in saliva 3 hours after peanut consumption. Peanut protein was completely removed from granite tables after cleaning with detergent, and levels were reduced but still present after detergent cleaning of laminate and wooden table surfaces, pillows, and sofa covers. CONCLUSIONS Peanut spread easily around the home and might be resistant to usual cleaning methods. Peanut protein can be transferred into the environment by means of hand transfer and saliva but is unlikely to be aerosolized.

Dietary management of peanut and tree nut allergy: What exactly should patients avoid?

Peanut and tree nut allergies are the commonest cause of life‐threatening food‐allergic reactions and significantly affect quality of life in children and their families. Dietary nut avoidance and provision of emergency medication is currently the mainstay of treatment. Nut avoidance has consequences on both quality of life and nutrition. We review the terminology that may cause confusion and lead to unnecessary dietary restrictions. In peanut or tree nut‐allergic children, introduction of specific nuts to which the child is not allergic may improve quality of life and should be considered in patients with multiple foods allergies, vegan or ethnic‐specific diets, in whom nuts are an important source of protein. Nut‐allergic consumers do not just need to avoid foods containing nuts as an ingredient, but also contend with pre‐packed foods which frequently have precautionary allergen labelling (PAL) referring to possible nut contamination. Although the published rate of peanut contamination in ‘snack’ foods with PAL (see Box ) ranges from 0.9–32.4%, peanut contamination in non‐snack items with PAL is far less common. We propose that in some peanut‐allergic patients (depending on history of reactivity to trace levels of peanut, reaction severity, other medical conditions, willingness to always carry adrenaline, etc.), consideration may be given to allow the consumption of non‐snack foods containing PAL following discussion with the patients (and their familys) specialist. More work is needed to provide consumers with clearer information on the risk of potential nut contamination in pre‐packed food. We also draw attention to the change in legislation in December 2014 that require mandatory disclosure of allergens in non‐pre‐packed foods.

Antihistamine use in children

This review provides an overview of the use of antihistamines in children. We discuss types of histamine receptors and their mechanism of action, absorption, onset and duration of action of first-generation and second-generation H(1)-antihistamines, as well as elimination of H(1)-antihistamines which has important implications for dosing in children. The rationale for the use of H(1)-antihistamines is explored for the relief of histamine-mediated symptoms in a variety of allergic conditions including: non-anaphylactic allergic reactions, atopic eczema (AE), allergic rhinitis (AR) and conjunctivitis, chronic spontaneous urticaria (CSU) and whether they have a role in the management of intermittent and chronic cough, anaphylaxis, food protein-induced gastrointestinal allergy and asthma prevention. Second-generation H(1)-antihistamines are preferable to first-generation H(1)-antihistamines in the management of non-anaphylactic allergic reactions, AR, AE and CSU due to: their better safety profile, including minimal cognitive and antimuscarinic side effects and a longer duration of action. We offer some guidance as to the choices of H(1)-antihistamines available currently and their use in specific clinical settings. H(1)-antihistamine class, availability, licensing, age and dosing administration, recommended indications in allergic conditions and modalities of delivery for the 12 more commonly used H(1)-antihistamines in children are also tabulated.