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Development and validation of the Food Allergy Severity Score

Development and validation of the Food Allergy Severity Score
Development and validation of the Food Allergy Severity Score

Background: the heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. 

Methods: following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. 

Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10 −6–1.23 × 10 −3). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. 

Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

allergic reactions, anaphylaxis, food allergy, score, severity
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Fernández-Rivas, Montserrat
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Gómez García, Ismael
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Asero, Riccardo
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Turner, Paul J
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Fernández-Rivas, Montserrat
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Fuentes Ferrer, Manuel
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Asero, Riccardo
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Turner, Paul J
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Fernández-Rivas, Montserrat, Gómez García, Ismael, Gonzalo-Fernández, Alejandro, Fuentes Ferrer, Manuel, Dölle-Bierke, Sabine, Marco-Martín, Guadalupe, Ballmer-Weber, Barbara K, Asero, Riccardo, Belohlavkova, Simona, Beyer, Kirsten, de Blay, Frédéric, Clausen, Michael, Datema, Mareen R, Dubakiene, Ruta, Grimshaw, Kate E C, Hoffmann-Sommergruber, Karin, Hourihane, Jonathan O'B, Jedrzejczak-Czechowicz, Monika, Knulst, André C, Kralimarkova, Tanya, Le, Thuy-My, Papadopoulos, Nikolaos G, Popov, Todor A, Poulsen, Lars K, Purohit, Ashok, Seneviratne, Suranjith L, Simpson, Angela, Sinaniotis, Atanasios, Turkalji, Mirjana, Vázquez-Cortés, Sonia, Vera-Berrios, Rosialzira N, Muraro, Antonella, Worm, Margitta, Roberts, Graham, van Ree, Ronald, Fernández-Pérez, Cristina, Turner, Paul J and Mills, E N Clare (2021) Development and validation of the Food Allergy Severity Score. Allergy. (doi:10.1111/all.15165).

Record type: Article

Abstract

Background: the heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. 

Methods: following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. 

Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10 −6–1.23 × 10 −3). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. 

Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

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e-pub ahead of print date: 30 October 2021
Additional Information: Funding Information: Dr Fernández‐Rivas reports research grant to her institution from EU FP7 for the iFAAM project related to the work reported in this manuscript; research grants to her institution from Spanish Government (MINECO, ISCIII), and Aimmune Therapeutics and Diater, consultancy fees from Aimmune Therapeutics, Novartis and SPRIM, fees for participation in DSMB from DBV, lecture fees from Aimmune Therapeutics, ALK, Allergy Therapeutics, Diater, GSK, HAL Allergy and Thermo Fisher Scientific, outside the submitted work. Dr. Beyer reports grants/research supports from Aimmune Therapeutics, Danone/Nutricia/Milupa, DBV, Hipp, Hycor, Infectopharm and honoraria or consultation fees from Aimmune Therapeutics, Bencard, Danone/Nutricia/Milupa, DBV, Hipp, Hycor, Infectopharm, Jenapharma, Mylan/Meda, Nestle, Novartis, Thermo Fisher outside of the submitted work. Dr de Blay reports advisory board membership of Aimmune Therapeutics, Stallergènes Greer, Mundipharma, Novartis, Regeneron, DVB, Sanofi, ALK, Boehringer, and AstraZeneca, outside the submitted work. Dr Hourihane reports research funding from Aimmune Therapeutics, DBV Technologies, Johnson&Johnson, Dublin Skin and Cancer Hospital Charity, National Children's Research Centre, Dublin, Ireland, Temple St Hospital Foundation Charity and Clemens von Pirquet Foundation; advisory board membership of Aimmune Therapeutics; speaker bureaux of Aimmune Therapeutics, DBV Technologies and Danone‐Nutricia, outside the submitted work. Dr Papadopoulos reports research Support from Gerolymatos Int, Capricare, Nutricia, Vian; Speaker/Chairperson fees from HAL, Menarini/Faes Farma, MSD, Biomay, Novartis, Nutricia, Sanofi, Boehringer Ingelheim, Mylan/Meda, Asit Biotech; Advisory board fees from HAL, Menarini/Faes Farma, Novartis, Nutricia, GSK, AstraZeneca, Mylan/Meda, outside the submitted work. Prof. Worm declares the receipt of honoraria or consultation fees by the following companies: ALK‐Abelló Arzneimittel GmbH, Mylan Germany GmbH, Leo Pharma GmbH, Sanofi‐Aventis Deutschland GmbH, Regeneron Pharmaceuticals, DBV Technologies S.A, Stallergenes GmbH, HAL Allergie GmbH, Allergopharma GmbH & Co.KG, Bencard Allergie GmbH, Aimmune Therapeutics UK Limited, Actelion Pharmaceuticals Deutschland GmbH, Novartis AG, Biotest AG., AbbVie Deutschland GmbH & Co. KG and Lilly Deutschland GmbH, outside the submitted work. Prof. Roberts reports funding to his institution by the European Commission and the UK Food Standards Agency to undertake research as part of iFAAM, for the reported work in this manuscript. Dr van Ree reports research grant from EU FP7 for the iFAAM Project for the reported work in this manuscript; research grants from EU FP7, Dutch Science Foundation, and Health Holland, a research contract from Agany Inc., consulting fees from HAL Allergy BV, Citeq BV, Angany Inc., lecture fees from HAL Allergy BV, ALK and Thermo Fisher Scientific, support for attending meetings from HAL Allergy BV, advisory board fees from HAL Allergy BV and Agany Inc., stock options from Agany Inc., outside the submitted work. Dr Turner reports grants from European Commission H2020 iFAAM collaboration for the reported work in this manuscript; grants from UK Medical Research Council, NIHR/Imperial BRC, and UK Food Standards Agency; advisory board fees from ILSI Europe, Aimmune Therapeutics, and AllerGenis, outside the submitted work. Dr. Mills owns founder shares in Reacta Biotech Ltd, a company developing oral food challenge diagnostics for food allergy. Funding for research and consultancy is received from the company through the University of Manchester. All other authors declare no conflicts of interest. Funding Information: The authors wish to thank Prof. Marek L. Kowalski (deceased June 22nd, 2021) for his contribution in the EuroPrevall and iFAAM projects; Audrey DunnGalvin, Lynn Regent, Angel Sánchez, and Sabine Schnadt for their participation in the discussions on severity scoring within the iFAAM project, and Irene Serrano for the technical review of the FASS tool. The development and evaluation of FASS were undertaken as part of the European Union funded project iFAAM (312147), and the subsequent validation was done within the ARADyAL Research Network (RD16/0006/0009) and the BIOGRIAL‐SEVERAL (PI19/01095) project cofounded by the Instituto de Salud Carlos III, Ministry of Science of the Spanish Government and FEDER (European Regional Development Fund). Publisher Copyright: © 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: allergic reactions, anaphylaxis, food allergy, score, severity

Identifiers

Local EPrints ID: 452213
URI: http://eprints.soton.ac.uk/id/eprint/452213
ISSN: 0105-4538
PURE UUID: b2cb29f0-b16b-4f8c-9f5b-dd6683e33306
ORCID for Graham Roberts: ORCID iD orcid.org/0000-0003-2252-1248

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Date deposited: 30 Nov 2021 17:31
Last modified: 16 Apr 2024 01:39

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Contributors

Author: Montserrat Fernández-Rivas
Author: Ismael Gómez García
Author: Alejandro Gonzalo-Fernández
Author: Manuel Fuentes Ferrer
Author: Sabine Dölle-Bierke
Author: Guadalupe Marco-Martín
Author: Barbara K Ballmer-Weber
Author: Riccardo Asero
Author: Simona Belohlavkova
Author: Kirsten Beyer
Author: Frédéric de Blay
Author: Michael Clausen
Author: Mareen R Datema
Author: Ruta Dubakiene
Author: Karin Hoffmann-Sommergruber
Author: Jonathan O'B Hourihane
Author: Monika Jedrzejczak-Czechowicz
Author: André C Knulst
Author: Tanya Kralimarkova
Author: Thuy-My Le
Author: Nikolaos G Papadopoulos
Author: Todor A Popov
Author: Lars K Poulsen
Author: Ashok Purohit
Author: Suranjith L Seneviratne
Author: Angela Simpson
Author: Atanasios Sinaniotis
Author: Mirjana Turkalji
Author: Sonia Vázquez-Cortés
Author: Rosialzira N Vera-Berrios
Author: Antonella Muraro
Author: Margitta Worm
Author: Graham Roberts ORCID iD
Author: Ronald van Ree
Author: Cristina Fernández-Pérez
Author: Paul J Turner
Author: E N Clare Mills

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