Barbara K Ballmer-Weber1, Montserrat Fernandez-Rivas2, Kirsten Beyer3, Marianne Defernez4, Matthew Sperrin5, Alan R Mackie4, Louise J Salt4, Jonathan O'B Hourihane6, Riccardo Asero7, Simona Belohlavkova8, Marek Kowalski9, Frédéric de Blay10, Nikolaos G Papadopoulos11, Michael Clausen12, André C Knulst13, Graham Roberts14, Ted Popov15, Aline B Sprikkelman16, Ruta Dubakiene17, Stefan Vieths18, Ronald van Ree19, René Crevel20, E N Clare Mills21. 1. Allergy Unit, Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 2. Allergy Department, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. 3. Department of Paediatric Pneumology and Immunology, Charité University Medical Center, Berlin, Germany. 4. Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom. 5. Institute of Population Health, University of Manchester, Manchester, United Kingdom. 6. University College Cork, Cork, Ireland. 7. Ambulatorio di Allergologia, Clinica San Carlo, Paderno-Dugnano, Milan, Italy. 8. Faculty Hospital Bulovka, Department of Pediatrics, Prague, Czech Republic. 9. Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland. 10. Chest Disease Department, University Hospital, Federation of Translational Medicine, University of Strasbourg, Strasbourg, France. 11. Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece. 12. Children's Hospital Iceland, Landspitali, University Hospital, Reykjavik, Iceland. 13. University Medical Center Utrecht, Department of Dermatology/Allergology, Utrecht, The Netherlands. 14. Human Development and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom. 15. Medical University, Clinical Centre of Allergology of the Alexandrovska Hospital, Sofia, Bulgaria. 16. Department of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 17. Chest Clinics, Allergology and Radiology, Medical Faculty, Vilnius University, Vilnius, Lithuania. 18. Paul Ehrlich Institute, Langen, Germany. 19. Department of Experimental Immunology and Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 20. Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, United Kingdom. 21. Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom; Institute of Inflammation and Repair, Manchester Academic Health Science Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom. Electronic address: clare.mills@manchester.ac.uk.
Abstract
BACKGROUND: Precautionary labeling is used to warn consumers of the presence of unintended allergens, but the lack of agreed allergen thresholds can result in confusion and risk taking by patients with food allergy. The lack of data on threshold doses below which subjects are unlikely to react is preventing the development of evidence-based allergen management strategies that are understood by clinician and patient alike. OBJECTIVE: We sought to define threshold dose distributions for 5 major allergenic foods in the European population. METHODS: Patients with food allergy were drawn from the EuroPrevall birth cohort, community surveys, and outpatient clinic studies and invited to undergo a food challenge. Low-dose, double-blind, placebo-controlled food challenges were undertaken with commercially available food ingredients (peanut, hazelnut, celery, fish, and shrimp) blinded into common matrices. Dose distributions were modeled by using interval-censoring survival analysis with 3 parametric approaches. RESULTS: Of the 5 foods used for challenge, 4 produced similar dose distributions, with estimated doses eliciting reactions in 10% of the allergic population (ED10), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut, and celery with overlapping 95% CIs. ED10 values for fish were somewhat higher (27.3 mg of protein), although the CIs were wide and overlapping between fish and plant foods. Shrimp provided radically different dose distributions, with an ED10 value of 2.5 g of protein. CONCLUSION: This evidence base will contribute to the development of reference doses and action levels for allergens in foods below which only the most sensitive subjects might react.
BACKGROUND: Precautionary labeling is used to warn consumers of the presence of unintended allergens, but the lack of agreed allergen thresholds can result in confusion and risk taking by patients with food allergy. The lack of data on threshold doses below which subjects are unlikely to react is preventing the development of evidence-based allergen management strategies that are understood by clinician and patient alike. OBJECTIVE: We sought to define threshold dose distributions for 5 major allergenic foods in the European population. METHODS: Patients with food allergy were drawn from the EuroPrevall birth cohort, community surveys, and outpatient clinic studies and invited to undergo a food challenge. Low-dose, double-blind, placebo-controlled food challenges were undertaken with commercially available food ingredients (peanut, hazelnut, celery, fish, and shrimp) blinded into common matrices. Dose distributions were modeled by using interval-censoring survival analysis with 3 parametric approaches. RESULTS: Of the 5 foods used for challenge, 4 produced similar dose distributions, with estimated doses eliciting reactions in 10% of the allergic population (ED10), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut, and celery with overlapping 95% CIs. ED10 values for fish were somewhat higher (27.3 mg of protein), although the CIs were wide and overlapping between fish and plant foods. Shrimp provided radically different dose distributions, with an ED10 value of 2.5 g of protein. CONCLUSION: This evidence base will contribute to the development of reference doses and action levels for allergens in foods below which only the most sensitive subjects might react.
Authors: Shelley Dua; Monica Ruiz-Garcia; Simon Bond; Stephen R Durham; Ian Kimber; Clare Mills; Graham Roberts; Isabel Skypala; James Wason; Pamela Ewan; Robert Boyle; Andrew Clark Journal: J Allergy Clin Immunol Date: 2019-07-15 Impact factor: 10.793
Authors: Benjamin C Remington; Joost Westerhout; Marie Y Meima; W Marty Blom; Astrid G Kruizinga; Matthew W Wheeler; Steve L Taylor; Geert F Houben; Joseph L Baumert Journal: Food Chem Toxicol Date: 2020-03-13 Impact factor: 6.023
Authors: Nagib Ahsan; R Shyama Prasad Rao; Philip A Gruppuso; Bharat Ramratnam; Arthur R Salomon Journal: J Proteomics Date: 2016-04-22 Impact factor: 4.044
Authors: Joana Costa; Caterina Villa; Kitty Verhoeckx; Tanja Cirkovic-Velickovic; Denise Schrama; Paola Roncada; Pedro M Rodrigues; Cristian Piras; Laura Martín-Pedraza; Linda Monaci; Elena Molina; Gabriel Mazzucchelli; Isabel Mafra; Roberta Lupi; Daniel Lozano-Ojalvo; Colette Larré; Julia Klueber; Eva Gelencser; Cristina Bueno-Diaz; Araceli Diaz-Perales; Sara Benedé; Simona Lucia Bavaro; Annette Kuehn; Karin Hoffmann-Sommergruber; Thomas Holzhauser Journal: Clin Rev Allergy Immunol Date: 2021-01-07 Impact factor: 8.667