Background: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort. Methods: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales and were generally well exclusively breastfed babies recruited at 3 months old and followed up until 11 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12m, 36m and 7-11y. Results: The prevalence of PA was 2.1% with only 1 child having PA resolution at 7-11y. PA children had larger SPT size, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p<0.001) compared to PS children at 36m and 7-11y. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant at both 36m and 7-11y (p<0.001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36m. New PA children had increased SPT and peanut-sIgE from 36m to 7-11y, but MAT remained low. PS children had low biomarkers across time. Conclusions: In this cohort, few children outgrow or develop new PA between 36m and 7-11y. Children with PA have significantly higher SPT, peanut-sIgE, Ara h 2-sIgE and MAT compared to PS children, evident from 12-36m of age.

Background Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions. Objective: To evaluate the impact on gradual home introduction of foods containing cows milk after a supervised, single low dose exposure to whole milk at time of diagnosis. Methods Infants less than 12 months old, referred with suspected IgE-mediated cow’s milk allergy were recruited to an open-label randomised, controlled trial of intervention - a single dose of fresh cow’s milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED 05 – vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at Home. Parents completed food allergy quality of life and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post randomisation. Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects had reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). Twelve months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p=0.03). Maternal STAIs were significantly associated with their infants’ progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion This study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows milk allergy in a very young cohort. A supervised single dose of milk at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards completion of the milk ladder, but pre-existing high levels of maternal anxiety are associated with poorer progress.

Background Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions. Objective: To evaluate the impact on gradual home introduction of foods containing cows milk after a supervised, single low dose exposure to whole milk at time of diagnosis. Methods Infants less than 12 months old, referred with suspected IgE-mediated cow’s milk allergy were recruited to an open-label randomised, controlled trial of intervention - a single dose of fresh cow’s milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED 05 – vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at Home. Parents completed food allergy quality of life and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post randomisation. Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects had reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). Twelve months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p=0.03). Maternal STAIs were significantly associated with their infants’ progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion This study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows milk allergy in a very young cohort. A supervised single dose of milk at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards completion of the milk ladder, but pre-existing high levels of maternal anxiety are associated with poorer progress.

Background: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. EDs can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED05 values for cow’s milk (the dose expected to cause objective allergic symptoms in 5% of the milk-allergic population) range from 0.5mg to 13.9mg cow’s milk protein. We undertook a single-dose challenge study to validate a predicted ED05 for cow’s milk of 0.5mg protein. Methods: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5mg cow’s milk protein (approximately 0.015ml of fresh cow’s milk). Children over 1 year underwent formal challenge to cow’s milk to confirm clinical reactivity. Results: 172 children (median age 6 (IQR 0.7-11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7-11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis which responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitisation which were associated with objective reactivity to the single-dose challenge using 0.5mg cow’s milk protein. Conclusions: These data support an estimated ED05 for cow’s milk of 0.5mg protein. Values for ED05 above 0.5mg for cow’s milk protein proposed for allergen risk management need to be reviewed.