Single-dose oral challenges to validate eliciting doses in children with cow's milk allergy.

Paul J Turner,Ronald Van Ree,Sophia A Chastell,Rosialzira N Vera‐Berrios,Marta Vazquez‐Ortiz,Clare E N Mills,Montserrat Fernandez‐Rivas,Guadalupe Marco‐Martin,Olaya Alvarez,Joseph L Baumert,Bettina Duca,Raphaëlle Bazire,Pablo Rodríguez Del Río,Jonathan O'B Hourihane,Yvonne M D'Art,Motohiro Ebisawa

doi:10.1111/pai.13482

Abstract

There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. The ED 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. 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 1year underwent formal challenge to cow's milk to confirm clinical reactivity. 172 children (median age 6.0 (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 that 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 sensitization that were associated with objective reactivity to the single-dose challenge using 0.5mg cow's milk protein. 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.

Highlights

There is increasing interest in the use of routinely collected clinical data from oral food challenges (OFC) to inform both patient management and allergen risk management in industry, in terms of the level of dietary allergen avoidance required
The observed proportion of patients reacting to 0.5 mg cow's milk protein with predetermined objective criteria was 7.0%
This is within the statistical bounds for the original estimated ED05 of 0.5 mg cow's milk protein that would result in 5% of the milk-allergic population reacting with objective symptoms

Summary

Introduction

There is increasing interest in the use of routinely collected clinical data from oral food challenges (OFC) to inform both patient management and allergen risk management in industry, in terms of the level of dietary allergen avoidance required. The PRACTALL consensus recommends a starting dose of 3 mg food protein for OFC,[6] but data suggest that for cow's milk protein allergy (CMPA), this may cause objective symptoms in 10% of allergic individuals.[7]. These data are ‘left-censored’ and cause greater uncertainty when estimating a level of exposure, which causes symptoms in a small proportion of the allergic population.[5].

Methods

Findings

Discussion

Conclusion