The Impact of Histological Grade on Outcomes


The following is a summary of “Reproducibility of food challenge to cow’s milk: Systematic review with individual participant data meta-analysis,” published in the November 2022 issue of Allergy and clinical immunology by Turner, et al.

There was ambiguity regarding the severity of responses at low-level CM exposure as well as the repeatability of reaction thresholds. Cow’s milk (CM) is a common source of severe allergic reactions. For a study, researchers sought to ascertain the frequency of anaphylaxis to low-level exposures and the repeatability of response thresholds, so they conducted an individual participant data (IPD) meta-analysis of studies reporting double-blind, placebo-controlled food challenges in CM.

They conducted an IPD meta-analysis and systematic evaluation of papers providing pertinent data. They contacted the authors for any further information or clarification required. The National Institute for Clinical Excellence methodological criteria were used to evaluate the risk of bias.

There was 34 research included, totaling more than 1,000 participants’ data. The cumulative ED01 and ED05 (i.e., cumulative doses inducing objective symptoms in 1% and 5%, respectively, of the at-risk allergy group) were 0.3 (95% CI, 0.2-0.5) and 2.9 (95% CI, 1.6-5.4) mg, respectively. Anaphylaxis occurred in 4.8% (95% CI, 2.0–10.9) and 4.8% (95% CI, 0.7–27.1) of people who reacted to ≤5 mg and ≤0.5 mg of CM protein, respectively (minimum heterogeneity, I2 = 0%), at the meta-analysis. Then 110 people undertook further double-blind, placebo-controlled meal challenges; the intraindividual variation in reaction threshold was limited to a ½-log change in 80% (95% CI, 65-89) of the cases, the intraindividual variation in response threshold was confined to a 1-log change. Although none of the two people developed anaphylaxis, they first tolerated 5 mg of CM protein before reacting to it during a later test.

Anaphylaxis may occur at ED01 or ED05 in around 5% of CM-allergic people who respond to such doses. In the larger CM-allergic population, it translated to 5 and 24 anaphylactic incidents per 10,000 individuals exposed to an ED01 or ED05 dosage, respectively. A single dosage of epinephrine would usually be sufficient to treat the majority of these minor anaphylactic responses.


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