Allergen specificity of early peanut consumption and effect on development of allergic disease in the Learning Early About Peanut Allergy study cohort

Abstract

Background: Early introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented peanut allergy at 5 years of age in the Learning Early About Peanut Allergy (LEAP) study. The protective effect persisted after 12 months of avoiding peanuts in the 12-month extension of the LEAP study (LEAP-On). It is unclear whether this benefit is allergen and allergic disease specific.

Objective: We sought to assess the effect of early introduction of peanut on the development of allergic disease, food sensitization, and aeroallergen sensitization.

Methods: Asthma, eczema, and rhinoconjunctivitis were diagnosed based on clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food allergens and aeroallergens was determined by means of skin prick testing and specific IgE measurement.

Results: A high and increasing burden of food allergen and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least 1 allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts, with levels being higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants and was not affected by peanut consumption.

Conclusion: Early consumption of peanut in infants at high risk of peanut allergy is allergen specific and does not prevent the development of other allergic disease, sensitization to other food allergens and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy.

Keywords: Food allergy; allergen-specific asthma; allergy prevention; atopic dermatitis; eczema; peanut allergy; rhinoconjunctivitis; tolerance.

Figure 1. Asthma and Rhinoconjunctivitis Burden Over Time

The rate of protocol-defined asthma, seasonal rhinoconjunctivitis and perennial rhinoconjunctivitis in the consumption (green bars) and avoidance (gray bars) groups in the ITT population at 30, 60 and 72 months are shown. There are no significant differences between the two groups at any time point as assessed by Chi-Squared Tests.

Figure 2. Eczema Severity Bands Over Time (SCORAD)

The percent of individuals with SCORAD assessments for eczema of 0, >0–15, ≥15–40 and >40 are shown at baseline and at 12, 30, 60 and 72 months in the avoidance (left bar of each pair) and consumption groups (right bar of each pair) in the ITT population. There are no significant differences between the two groups at any time point as assessed by Chi-Squared Tests.

Figure 3. Peanut SPT, Peanut S-IgE, and Ara h2 S-IgE

Peanut SPT (top panel), Peanut IgE (middle panel), and Ara h2 IgE (bottom panel) in the consumption and avoidance groups in the ITT (left column) and LEAP Per Protocol (right column) populations at 4–11, 12, 30, 60, and 72 months are shown. Boxes represent 25th and 75th centiles and error bars represent 2.5th and 97.5^th centiles. Lines connect the means over time for each randomized group. Solid grey lines represent the LEAP avoiders. Dashed green lines represent LEAP consumers. Grey circles represent LEAP avoiders. Green circles represent LEAP consumers. The ‘*’ represent a p-value ≤0.05 resulting from a comparison between the LEAP avoidance and LEAP consumption groups using a two sample t-test. The ‘**’ represent a p-value ≤0.01 resulting from a comparison between the LEAP avoidance and LEAP consumption groups using a two sample t-test.

Figure 4. Tree Nut and Sesame SPT (mm)

Sesame, Brazil nut, Walnut, Cashew, Almond, and Hazelnut SPT (mm) results in the consumption and avoidance groups in the ITT (top row) and LEAP Per Protocol (bottom row) populations at 4–11, 12, 30, 60, and 72 months is shown for Sesame and at 60 and 72 months for the other Tree Nut outcomes. Boxes represent 25th and 75th centiles and error bars represent 2.5th and 97.5^th centiles. Lines connect the means over time for each randomized group. Solid grey lines represent the LEAP avoiders. Dashed green lines represent LEAP consumers. Grey circles represent LEAP avoiders. Green circles represent LEAP consumers. The ‘*’ represent a p-value ≤0.05 resulting from a comparison between the LEAP avoidance and LEAP consumption groups using a two sample t-test. The ‘**’ represent a p-value ≤0.01 resulting from a comparison between the LEAP avoidance and LEAP consumption groups using a two sample t-test.

Figure 5. Tree Nut and Sesame Specific IgE (kU/L)

Sesame, Brazil nut, Walnut, Cashew, Almond, and Hazelnut specific IgE (kU/L) in the consumption and avoidance groups in the ITT (top row) and LEAP Per Protocol (bottom row) populations at 4–11, 12, 30, 60, and 72 months are shown. Boxes represent 25th and 75th centiles and error bars represent 2.5th and 97.5^th centiles. Lines connect the means over time for each randomized group. Solid grey lines represent the LEAP avoiders. Dashed green lines represent LEAP consumers. Grey circles represent LEAP avoiders. Green circles represent LEAP consumers. The ‘*’ represent a p-value ≤0.05 resulting from a comparison between the LEAP avoidance and LEAP consumption groups using a two sample t-test. The ‘**’ represent a p-value ≤0.01 resulting from a comparison between the LEAP avoidance and LEAP consumption groups using a two sample t-test.

Figure 6. Aeroallergen Sensitization

The prevalence of IgE ≥0.35 for several aeroallergens in the consumption (green bars) and avoidance (gray bars) groups at 30, 60 and 72 months are shown. There are no significant differences between the two groups at any time point as assessed by Chi-Squared Tests.

Figure 7. Cumulative Burden Venn Diagram at 60 Months of Age

The number of participants in the ITT population with protocol defined eczema, rhinoconjunctivitis, asthma or any likely food allergy are shown for the avoidance group (top left), consumption group (top right) and total study group (bottom). This illustrates the very high rate of single and multiple allergic diseases in the study population. Figures are numbers (percentage) of participants.

Figure 8. Peanut and Egg Allergy Associations with Development of Allergic Diseases

The rate of protocol-defined asthma (left), seasonal rhinoconjunctivitis (middle) and perennial rhinoconjunctivitis (right) at 60 (top) and 72 (bottom) months are shown in those with neither egg nor peanut allergy, egg allergy only, peanut allergy only or both egg and peanut allergy. The number of subjects contributing to each group is presented in the denominator while the number of subjects with each allergic disease within each group is presented in the numerator of the values annotated within each bar. Presence of egg allergy was defined per inclusion criteria at baseline, whereas peanut allergy was defined at 60 and 72 months. P-values resulting from a multivariate logistic regression model (outcome of interest being each allergic disease) adjusted for peanut allergy, baseline egg allergy and baseline SCORAD are annotated within each panel.