disclosures: Turner reports that he has received grants from JM Charitable Foundation, NIH, Care Research/Imperial Biomedical Research Center and UK Medical Research Council. See the study for the relevant financial disclosures from all other authors.
According to a study in The Journal of Allergy and Clinical Immunology†
Most of these anaphylactic reactions are said to be mild and can be treated with a single dose of epinephrine, Paul J. Turner, FRCPCH, PhD, from the National Heart & Lung Institute at Imperial College London, and colleagues wrote.
To determine the degree of anaphylaxis for love-level exposures and the reproducibility of response thresholds, the researchers reviewed 34 studies describing 1002 double-blind, placebo-controlled food challenges (DBPCFCs) for cow’s milk (CM), published between January 1984 and December 2021.
Overall, these challenges to cumulative eliciting doses affected the amount of CM protein predicted to cause objective symptoms in 1% of the CM-allergic population (ED01) of 0.3 mg (95% CI, 0.2-0.5) and in 5% of the CM-allergic population (ED05) of 2.9 mg (95% CI, 1.6-5.4).
Researchers then rated the degree of anaphylaxis to low-level exposures based on the upper 95% CIs of ED01 (0.5mg) and ED05 (5mg).
In 14 of the studies, 105 subjects responded to 5 mg or less of CM protein, with 4.8% (95% CI, 2%-10.9%) having an anaphylactic reaction. In three other studies, 4.8% (95% CI, 0.7%-27.1%) of responses to 0.5 mg or less of CM protein were anaphylactic.
Researchers then tested the reproducibility of these response thresholds using data from five interventional studies involving participants who had a repeated food challenge for CM between 5 and 12 months after an initial baseline challenge. With a median cumulative response threshold of 144 mg CM protein (interquartile range, 44 mg-444 mg), they had an overall anaphylaxis rate of 14.5%.
During repeated challenges, 80% of the participants responded within ± one-half log increment of the initial challenge, which, according to the researchers, was equivalent to within one dosing interval. Also, the subjects who had responses to lower doses during their first DBPCFC were more likely to have responses to higher doses during the repeated challenge with an increase of ± one-half log or greater from the response threshold.
The researchers observed four individuals who had responses to 5 mg or less during their first challenge and then responded to 5 mg or more during a later challenge. There were also two subjects who responded to 5 mg or less during a subsequent challenge, although they had initially tolerated that dose.
None of the individuals initially have an ED. tolerated05 exposure level had anaphylaxis for the same dose or less during a later challenge.
To assess the incidence of recurrent anaphylaxis, researchers reviewed three studies of repeated DBPCFCs in 33 participants with at least one anaphylaxis reaction, including four who had anaphylaxis during both challenges, with responses at the same threshold in both cases.
The researchers said the occurrence of anaphylaxis was not predictable; However, 17 of these patients (52%; 95% CI, 34%-69%) had anaphylaxis on the first but not the second exposure to the same or higher level of CM exposure.
Overall, the researchers determined an overall risk of anaphylaxis in the broader population of people with CM allergy of five events per 10,000 patients exposed to an ED01 dose and 24 events per 10,000 patients exposed to an ED05 dose, which corresponds to 2.9 mg of CM protein or 0.1 ml of fresh milk. Most anaphylactic reactions are said to be mild and responsive to a single dose of epinephrine, the researchers continued.
Furthermore, less than 5% of individuals would respond to a sub-ED05 level having previously tolerated it, and individuals who do respond would be “very unlikely” to have anaphylaxis, the researchers wrote.
The researchers expressed confidence in their results, noting the minimal heterogeneity they observed on meta-analysis and when comparing clearly defined criteria for the lowest observed level of side effects and dose-limiting symptoms.
The researchers also said these findings support the use of trigger doses to inform the need for preventive allergy labeling after food companies conduct formal allergen risk assessments. These findings could also be used to develop strategies for establishing evidence-based approaches to allergen management, the researchers continued.