Food anaphylaxis may be pathophysiologically different than anaphylaxis caused by nonfood triggers. Currently, there are no robust, clinically useful predictors of severity in food allergy. It is likely that patient-specific reaction phenotypes exist in food allergy, which may affect the risk of severe anaphylaxis. Allergen immunotherapy may modulate these phenotypes. Machine-based learning may help with endotype discovery in anaphylaxis.

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Regeneron; serves the American College of Allergy, Asthma, and Immunology as deputy editor of the Annals of Allergy, Asthma, and Immunology and is a member of the American Board of Allergy and Immunology outside the submitted work; and is on the medical advisory board (unpaid) of the International FPIES Association. L. Lange Background: Tolerance development is an important clinical outcome for infants with cow's milk allergy. Objective: This multicenter, prospective, randomized, doubleblind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acidbased formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgEmediated CM allergy. Methods: Subjects aged < _13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n 5 80) or AAF (n 5 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. A logistic regression model used the all-subjects randomized data set. Results: At baseline, mean 6 SD age was 9.36 6 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P 5 .036). Conclusions: After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections. (J Allergy Clin Immunol 2021;nnn:nnn-nnn.)

Background: Regulatory bodies recommend that all patients at risk of anaphylaxis be prescribed 2 epinephrine autoinjectors, which they should carry at all times. This is in contrast to some guidelines. The proportion of anaphylaxis reactions that are treated with multiple doses of epinephrine has not been systematically evaluated. Objective: Our aim was to undertake a systematic review and meta-analysis of published studies reporting epinephrine treatment for anaphylaxis in which data relating to the number of doses administered were available. Methods: We searched the Medline, Embase, and Cochrane databases for relevant studies reporting at least 10 anaphylaxis events (due to food or venom) from 1946 until January 2020. Data were extracted in duplicate for the metaanalysis, and the risk of bias was assessed. The study was registered under the PROSPERO identifier CRD42017069109. Results: A total of 86 studies (36,557 anaphylaxis events) met the inclusion criteria (20 of the studies [23%] were prospective studies; 64 [74%] reported reactions in the community, and 22 [26%] included food challenge data). Risk of bias was assessed as low in 50 studies. Overall, 7.7% of anaphylaxis events from any cause (95% CI 5 6.4-9.1) were treated with multiple doses of epinephrine. When only epinephrine-treated reactions for which subsequent doses were administered by a health care professional were considered, 11.1% of food-induced reactions (95% CI 5 9.4-13.2) and 17.1% of venom-induced reactions (95% CI 5 11.3-25.0) were treated with at least 1 epinephrine dose. Heterogeneity was moderate to high in the meta-analyses, but at sensitivity analysis it was not affected by study design or anaphylaxis definition. Conclusion: Around 1 in 10 anaphylaxis reactions are treated with at least 1 dose of epinephrine. (J Allergy Clin Immunol 2021;nnn:nnn-nnn.)