. 2022 May;77(5):1545-1558.

doi: 10.1111/all.15165. Epub 2021 Nov 12.

Development and validation of the food allergy severity score

Montserrat Fernández-Rivas¹, Ismael Gómez García², Alejandro Gonzalo-Fernández², Manuel Fuentes Ferrer³, Sabine Dölle-Bierke⁴, Guadalupe Marco-Martín⁵, Barbara K Ballmer-Weber^{6

7}, Riccardo Asero⁸, Simona Belohlavkova⁹, Kirsten Beyer¹⁰, Frédéric de Blay¹¹, Michael Clausen¹², Mareen R Datema¹³, Ruta Dubakiene¹⁴, Kate E C Grimshaw^{15

16}, Karin Hoffmann-Sommergruber¹⁷, Jonathan O'B Hourihane¹⁸, Monika Jedrzejczak-Czechowicz¹⁹, André C Knulst²⁰, Tanya Kralimarkova²¹, Thuy-My Le²⁰, Nikolaos G Papadopoulos^{22

23}, Todor A Popov²⁴, Lars K Poulsen²⁵, Ashok Purohit²⁶, Suranjith L Seneviratne^{27

28}, Angela Simpson²⁹, Atanasios Sinaniotis^{30

31}, Mirjana Turkalji³², Sonia Vázquez-Cortés⁵, Rosialzira N Vera-Berrios², Antonella Muraro³³, Margitta Worm⁴, Graham Roberts^{34

35

36}, Ronald van Ree³⁷, Cristina Fernández-Pérez^{38

39}, Paul J Turner⁴⁰, Elizabeth N Clare Mills⁴¹

Affiliations

¹ Allergy Department, Hospital Clínico San Carlos, Facultad de Medicina, Universidad Complutense (UCM), IdISSC, ARADyAL, Madrid, Spain.
² Grupo de Investigación en Alergia, IdISSC, Madrid, Spain.
³ Unidad de Apoyo a la Investigación, Preventive Medicine Department, Hospital Clínico San Carlos, IdISSC, Universidad Alfonso X El Sabio, Madrid, Spain.
⁴ Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁵ Allergy Department, Hospital Clínico San Carlos, IdISSC, ARADyAL, Madrid, Spain.
⁶ Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
⁷ Clinic for Dermatology and Allergology, Kantonsspital St Gallen, St Gallen, Switzerland.
⁸ Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Milan, Italy.
⁹ Medical Faculty and Faculty Hospital Pilsen, Pilsen, Czech Republic.
¹⁰ Department of Pediatric Respiratory Medicine, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹¹ Chest Diseases Department, Strasbourg University Hospital, Federation of Translational Medicine, University of Strasbourg, Strasbourg, France.
¹² Children's Hospital and Department of Allergy, Landspitali University Hospital, Reykjavik, Iceland.
¹³ Department of Experimental Immunology, and Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Center, Amsterdam, The Netherlands.
¹⁴ Medical Faculty, Vilnius University, Vilnius, Lithuania.
¹⁵ Department of Dietetics, Salford Royal NHS Foundation Trust, Salford, UK.
¹⁶ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁷ Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
¹⁸ Royal College of Surgeons in Ireland, Children's Health Ireland at Temple Street, Dublin, Ireland.
¹⁹ Department of Allergy and Immunology, Medical University of Lodz, Lodz, Poland.
²⁰ Dept. Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
²¹ Clinic of Allergy and Asthma, Medical University in Sofia, Sofia, Bulgaria.
²² Allergy Dpt, 2nd Pediatric clinic, University of Athens, Athens, Greece.
²³ Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
²⁴ University Hospital Sv. Ivan Rilski, Sofia, Bulgaria.
²⁵ Allergy Clinic, Copenhagen University Hospital at Herlev-Gentofte, Copenhagen, Denmark.
²⁶ Allergy Division, Chest Disease Department, University Hospital of Strasbourg, Strasbourg, France.
²⁷ Department of Clinical Immunology and Allergy, Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester, UK.
²⁸ Institute of Immunity and Transplantation, Royal Free Hospital and University College London, London, UK.
²⁹ Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, and Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK.
³⁰ Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
³¹ Allergy Department, Sotiria Chest Diseases Hospital, Athens, Greece.
³² Srebrnjak Children's Hospital Zagreb, Catholic University of Croatia Zagreb, and Medical Faculty Osijek, J.J.Strossmayer University, Osijek, Croatia.
³³ Food Allergy Referral Centre Veneto Region, Department of Women and Child Health, Padua General University Hospital, Padua, Italy.
³⁴ NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³⁵ Clinical and Experimental Sciences and Human Development in Health, Faculty of Medicine, University of Southampton, Southampton, UK.
³⁶ The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, UK.
³⁷ Departments of Experimental Immunology and of Otorhinoraryngology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
³⁸ Preventive Medicine Department, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
³⁹ Preventive Medicine Department, Complejo Hospitalario Universitario Santiago de Compostela, Santiago de Compostela, Spain.
⁴⁰ National Heart & Lung Institute, Imperial College London, London, UK.
⁴¹ Division of Infection, Immunity and Respiratory Medicine, Manchester Academic Health Sciences Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK.

PMID: 34716996
PMCID: PMC9298738
DOI: 10.1111/all.15165

Development and validation of the food allergy severity score

Montserrat Fernández-Rivas et al. Allergy. 2022 May.

. 2022 May;77(5):1545-1558.

doi: 10.1111/all.15165. Epub 2021 Nov 12.

Authors

Affiliations

¹ Allergy Department, Hospital Clínico San Carlos, Facultad de Medicina, Universidad Complutense (UCM), IdISSC, ARADyAL, Madrid, Spain.
² Grupo de Investigación en Alergia, IdISSC, Madrid, Spain.
³ Unidad de Apoyo a la Investigación, Preventive Medicine Department, Hospital Clínico San Carlos, IdISSC, Universidad Alfonso X El Sabio, Madrid, Spain.
⁴ Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁵ Allergy Department, Hospital Clínico San Carlos, IdISSC, ARADyAL, Madrid, Spain.
⁶ Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
⁷ Clinic for Dermatology and Allergology, Kantonsspital St Gallen, St Gallen, Switzerland.
⁸ Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Milan, Italy.
⁹ Medical Faculty and Faculty Hospital Pilsen, Pilsen, Czech Republic.
¹⁰ Department of Pediatric Respiratory Medicine, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹¹ Chest Diseases Department, Strasbourg University Hospital, Federation of Translational Medicine, University of Strasbourg, Strasbourg, France.
¹² Children's Hospital and Department of Allergy, Landspitali University Hospital, Reykjavik, Iceland.
¹³ Department of Experimental Immunology, and Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Center, Amsterdam, The Netherlands.
¹⁴ Medical Faculty, Vilnius University, Vilnius, Lithuania.
¹⁵ Department of Dietetics, Salford Royal NHS Foundation Trust, Salford, UK.
¹⁶ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁷ Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
¹⁸ Royal College of Surgeons in Ireland, Children's Health Ireland at Temple Street, Dublin, Ireland.
¹⁹ Department of Allergy and Immunology, Medical University of Lodz, Lodz, Poland.
²⁰ Dept. Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
²¹ Clinic of Allergy and Asthma, Medical University in Sofia, Sofia, Bulgaria.
²² Allergy Dpt, 2nd Pediatric clinic, University of Athens, Athens, Greece.
²³ Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
²⁴ University Hospital Sv. Ivan Rilski, Sofia, Bulgaria.
²⁵ Allergy Clinic, Copenhagen University Hospital at Herlev-Gentofte, Copenhagen, Denmark.
²⁶ Allergy Division, Chest Disease Department, University Hospital of Strasbourg, Strasbourg, France.
²⁷ Department of Clinical Immunology and Allergy, Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester, UK.
²⁸ Institute of Immunity and Transplantation, Royal Free Hospital and University College London, London, UK.
²⁹ Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, and Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK.
³⁰ Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
³¹ Allergy Department, Sotiria Chest Diseases Hospital, Athens, Greece.
³² Srebrnjak Children's Hospital Zagreb, Catholic University of Croatia Zagreb, and Medical Faculty Osijek, J.J.Strossmayer University, Osijek, Croatia.
³³ Food Allergy Referral Centre Veneto Region, Department of Women and Child Health, Padua General University Hospital, Padua, Italy.
³⁴ NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³⁵ Clinical and Experimental Sciences and Human Development in Health, Faculty of Medicine, University of Southampton, Southampton, UK.
³⁶ The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, UK.
³⁷ Departments of Experimental Immunology and of Otorhinoraryngology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
³⁸ Preventive Medicine Department, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
³⁹ Preventive Medicine Department, Complejo Hospitalario Universitario Santiago de Compostela, Santiago de Compostela, Spain.
⁴⁰ National Heart & Lung Institute, Imperial College London, London, UK.
⁴¹ Division of Infection, Immunity and Respiratory Medicine, Manchester Academic Health Sciences Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK.

PMID: 34716996
PMCID: PMC9298738
DOI: 10.1111/all.15165

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.

Keywords: allergic reactions; anaphylaxis; food allergy; score; severity.

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Conflict of interest statement

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.

Figures

**FIGURE 1**
A, Model evaluation: ROC curves for oFASS‐3, oFASS‐5, and nFASS in the EuroPrevall outpatient clinic cohort. B, External validation: ROC curves for the severity indicators with nFASS. TPR, true‐positive rate; FPR, false‐positive rate; ROC, receiver operating characteristic, CMT, critical medical treatment

See this image and copyright information in PMC

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Development and validation of the food allergy severity score

Affiliations

Development and validation of the food allergy severity score

Authors

Affiliations

Abstract

Conflict of interest statement

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Grants and funding

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