Evaluation of a Standardized Bakery Product (SUTMEK) as a Potential Tool for Baked-Milk Tolerance and Immunotherapy Research Studies

Abstract

Background and Objectives: About 65–80% of children with IgE-mediated cow’s milk allergy (CMA) can tolerate extensively heated milk. We have invested in the mass fabrication of a test product containing milk protein baked at 180°C for 30 min (SUTMEK-milk) and a milk-free placebo (SUTMEK-placebo) to carry out a standardised double-blind placebo-controlled food challenge (DBPCFC) test in patients with CMA. Methods: We studied children with IgE-mediated CMA between 13 and 48 months of age. Specific IgEs (spIgE) to milk proteins were quantified. A DBPCFC with our bakery products was performed, and factors determining reactivity to extensively heated milk were evaluated. We also tested the applicability of SUTMEK products in baked-milk oral immunotherapy in a pilot assessment. Results: We studied 15 children (8 girls, 7 boys) with a median age of 26 months (range: 13–48 months). Nine (60%) patients tolerated a challenge with extensively heated milk, while 6 (40%) were found reactive (anaphylaxis: 2, wheezing: 2, urticaria: 2). spIgE to milk, α-lactalbumin, and casein, and the wheal diameter on skin prick testing were higher in the reactive group than the tolerant groups (p = 0.001, p = 0.001, p = 0.002, and p = 0.048, respectively). Receiver-operating characteristic curve analyses yielded the following cut-off values for spIgEs that would predict a reactivity to extensively heated milk; milk: 25 kU/L (area under curve, AUC: 0.981), casein: 32 kU/L (AUC: 0.983), and α-lactalbumin: 17 kU/L (AUC: 0.981). Nine patients have tolerated well a continued daily consumption of SUTMEK-milk or -placebo for 6 months at the desired doses. Conclusions: Our bakery products were successfully used in DBPCFC studies and qualified as an acceptable tool for use in the research of interventional tolerance induction. Although spIgE appears useful in determining children at high risk of reacting to extensively heated milk, the predictive cut-off values are still far from being perfect.

Systematic review and meta‐analyses on the accuracy of diagnostic tests for IgE‐mediated food allergy

“…The systematic search identified 1494 unique records. A total of 149 studies 31‐178 were included after application of our predefined eligibility criteria. Figure 1 illustrates the PRISMA meta‐analyses flowchart for the study screening and selection process.…”

“…For baked milk allergy, there were five studies available that met the inclusion criteria 40,70,96,105,155 . These studies were included in the systematic review, but no meta‐analysis was performed because three of these studies did not report diagnostic performance, namely sensitivity and specificity, for the index tests.…”

“…For baked milk allergy, there were five studies available that met the inclusion criteria. 40,70,96,105,155 These studies were included in the systematic review, but no meta-analysis was performed because F I G U R E 3 Forrest plots with sensitivity and specificity for the individual tests for the different foods (A: peanut, B: hen's egg, C: cow's milk, D: hazelnut, E: cashew nut, F: walnut G: sesame, H: soy, I: wheat, J: shrimp) For a test-food combination to be included in the meta-analyses, there needed to be a minimum of three studies. Data for hen's egg are showed separately for raw, cooked and baked egg allergies.…”

Introduction of Heated Cow’s Milk Protein in Challenge-Proven Cow’s Milk Allergic Children: The iAGE Study

“…Especially when baking products such as cakes, the internal temperature of the product may strongly differ from the surface temperature, leading to different heat-induced protein modifications throughout the product, which may even leave some of the CMP intact. For better understanding of the effect of baked milk on CMA, a standardized, heated and glycated CMP product should be produced, in which the extent of heat-induced modifications, including glycation, have been well characterized [6,16,[23][24][25].…”