Faculty Bibliography

BACKGROUND:Cow's milk allergy (CMA) is one of the most common food allergies world-wide. The emergence of online CMA symptom questionnaires, aimed at parents and/or healthcare professionals (HCP), may raise awareness about the possible diagnosis of CMA, but also increases the risk for overdiagnosis leading to unnecessary dietary restriction impacting on growth and nutrition. This publication sets out to establish the availability of these CMA symptom questionnaires and critically assesses the development and validity. METHODS:Thirteen HCP working in the field of CMA, from different countries, were recruited to participate. A combination of a Pubmed and CINAHL literature and online review using the Google search engine in English language was used. Symptoms in the questionnaires were assessed, using the European Academy for Allergy and Clinical Immunology guidelines for food allergy. Following the assessment of both the questionnaires and literature, the authors followed the modified Delphi approach to generate consensus statements. RESULTS:Six hundred and fifty-one publications were identified, of which 29 were suitable for inclusion, with 26 being associated with the Cow's Milk-Related Symptoms Score. The online search yielded 10 available questionnaires: 7/10 were sponsored by formula milk companies and 7/10 were aimed at parents and three at HCP. Following the assessment of data, 19 statements were generated in two rounds of anonymous voting reaching 100% agreement. CONCLUSIONS:Online CMA questionnaires, available to parents and HCP's, are varied in symptoms, and most were not validated. The overarching consensus generated from authors is that these questionnaires should not be used without the involvement of HCP.

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods: Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

Background: Patients with peanut allergy (PA) experience significant burden of illness, which impacts health-related quality of life (HRQoL), particularly in adolescence. There is a paucity of research evaluating drivers of HRQoL scores. Methods: A prospective, online survey of adolescents with self-reported, provider-diagnosed PA completed from November 2018 to January 2019 was used to explore drivers of the real-world impact of PA on HRQoL using the Pediatric Quality of Life Inventory 4.0 (PedsQL) and other measures. Univariate and multivariate analyses were used to identify potential factors associated with PedsQL scores and to understand the level of association. Results: A total of 102 adolescents were included. The final model included 10 variables: race, reported strict peanut avoidance, satisfaction with prophylaxis, moderate-to-severe reaction within the past 12 months, touching peanut as cause of most severe reaction, fear of reaction, age, gender, comorbidities, and daily life limitations. In total, three items were shown to be strong predictors of the PedsQL total score including cause of severe reaction was touching peanut (yes), level of agreement with avoiding peanut (completely agree), and satisfaction with prophylaxis (not very much/not at all). Conclusions: There is substantial heterogeneity in the impact of the burden of PA on PedsQL scores across patients. This indicates the importance of shared and individualized decision making for PA management to optimize outcomes and improve HRQoL.

BACKGROUND:Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Symptoms are distinct from IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with Th17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood. OBJECTIVE:To use an untargeted metabolomics approach to identify novel pathways associated with FPIES reactions. METHODS:Serum samples were obtained before, during, and after an oral food challenge (OFC) (10 FPIES and 10 asymptomatic subjects), and they were analyzed by untargeted metabolomics. Two-way ANOVA with false discovery rate (FDR) adjustment was used for analysis of metabolites. Stomach and duodenal biopsies from non-FPIES donors were stimulated with adenosine in vitro and serotonin measured by immunoassay. RESULTS:A total of 34 metabolites were increased during symptomatic FPIES OFCs compared to asymptomatic subjects, including inosine and urate of the purine signaling pathway. Expression of purine receptors P2RX7 and P2RY10 and the ectonucleotidase CD73 in peripheral blood was significantly reduced after OFC in FPIES patients. The serotonin metabolite 5-hydroxyindoleacetate was significantly elevated post-reaction. Adenosine stimulation of gastric and duodenal biopsies from non-FPIES donors induced a significant release of serotonin, suggesting a link between purinergic pathway activation and serotonin release. CONCLUSIONS:Activation of the purinergic pathway during FPIES reactions provides a possible mechanism connecting inflammation and vomiting symptoms by triggering serotonin release from gastric and duodenal mucosa. CLINICAL IMPLICATIONS/CONCLUSIONS:The link between gastrointestinal inflammation and FPIES symptoms via adenosine and serotonin suggests novel therapeutic approaches to FPIES by targeting purinergic receptors.