How much is too much? Threshold dose distributions for 5 food allergens - 03/04/15
Doi : 10.1016/j.jaci.2014.10.047
Barbara K. Ballmer-Weber, MD a, Montserrat Fernandez-Rivas, MD, PhD b, Kirsten Beyer, MD c, Marianne Defernez, PhD d, Matthew Sperrin, PhD e, Alan R. Mackie, PhD d, Louise J. Salt, PhD d, Jonathan O'B. Hourihane, MD f, Riccardo Asero, MD g, Simona Belohlavkova, MD h, Marek Kowalski, MD, PhD i, Frédéric de Blay, MD j, Nikolaos G. Papadopoulos, MD, PhD k, Michael Clausen, MD l, André C. Knulst, MD, PhD m, Graham Roberts, DM n, Ted Popov, MD, PhD o, Aline B. Sprikkelman, MD, PhD p, Ruta Dubakiene, DRmed Habil q, Stefan Vieths, PhD r, Ronald van Ree, PhD s, René Crevel, DIBT t, E.N. Clare Mills, PhD d, u, ⁎ 
a Allergy Unit, Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
b Allergy Department, Hospital Clinico San Carlos, IdISSC, Madrid, Spain
c Department of Paediatric Pneumology and Immunology, Charité University Medical Center, Berlin, Germany
d Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom
e Institute of Population Health, University of Manchester, Manchester, United Kingdom
f University College Cork, Cork, Ireland
g Ambulatorio di Allergologia, Clinica San Carlo, Paderno-Dugnano, Milan, Italy
h Faculty Hospital Bulovka, Department of Pediatrics, Prague, Czech Republic
i Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland
j Chest Disease Department, University Hospital, Federation of Translational Medicine, University of Strasbourg, Strasbourg, France
k Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece
l Children's Hospital Iceland, Landspitali, University Hospital, Reykjavik, Iceland
m University Medical Center Utrecht, Department of Dermatology/Allergology, Utrecht, The Netherlands
n Human Development and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom
o Medical University, Clinical Centre of Allergology of the Alexandrovska Hospital, Sofia, Bulgaria
p Department of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
q Chest Clinics, Allergology and Radiology, Medical Faculty, Vilnius University, Vilnius, Lithuania
r Paul Ehrlich Institute, Langen, Germany
s Department of Experimental Immunology and Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
t Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, United Kingdom
u Institute of Inflammation and Repair, Manchester Academic Health Science Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom
∗Corresponding author: E. N. Clare Mills, PhD, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, Manchester Institute of Biotechnology, University of Manchester, 131, Princess St, Manchester M1 7DN, United Kingdom.
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.
Le texte complet de cet article est disponible en PDF.Key words : Food, allergy, threshold, peanut, hazelnut, celeriac, fish, shrimp, EuroPrevall
Abbreviations used : DBPCFC, ED10, OAS
Plan
| Supported by the European Union through the EuroPrevall project (FOOD-CT-2005-514000) and the UK Food Standards Agency (FSA projects T07062 and T07046). The Lithuanian birth cohort was supported by unrestricted grants from Grida and MSD and the Dutch birth cohort by unrestricted grants from Nutricia Advanced Medical Nutrition Netherlands, AstraZeneca Netherlands, TEVA Netherlands, and GlaxoSmithKline Netherlands. M.D., A.R.M., L.J.S., and E.N.C.M. were partly funded by the UK Biological and Biotechnological Sciences Research Council through an Institute Strategic Programme Grant to the Institute of Food Research (BBS/E/F/00041800, BBS/E/F/00042204). |
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| Disclosure of potential conflict of interest: The study was done within a European Union project (FOOD-CT-2005-514000). B. K. Ballmer-Weber has received consultancy fees and lecture fees from Thermo Fisher. M. Fernandez-Rivas has received research support and travel support from the European Commission (EuroPrevall project FOOD-CT-2005-514000); has received research support from Instituto de Salud Carlos III, Spanish Ministry of Science; and has received lecture fees from GlaxoSmithKline and ALK-Abelló. K. Beyer is a board member for Danone; has received consultancy fees from Danone, ALK-Abelló, Meda Pharma, Unilever, HAL, and Hipp; has received research support from the European Union (FOOD-CT-2005-514000), the German Research Foundation, Berliner Sparkassen Stiftung, Danone, Thermo Fisher, Hycor Diagnostic Systems, the Foundation for the Treatment of Peanut Allergy, Hipp, and Infectopharm; has received lecture fees from Danone, HAL, Unilever, Infectopharm, CSL Behring, UCB, MedaPharma, MedUpdate, Thermo Fisher, ALK-Abelló, and Hipp; and has received travel support from the EAACI (European Academy of Allergy and Clinical Immunology), AAAAI (American Academy of Allergy, Asthma & Immunology), DGAKI, GPA, Danone, HAL, Unilever, Infectopharm, CSL Behring, UCB, MedaPharma, MedUpdate, Thermo Fisher, ALK, and Hipp. M. Defernez has received research support from the UK Food Standards Agency (T07062). M. Sperrin has received research support from the UK Food Standards Agency (T07062). A. R. Mackie has received research support, travel support, and participation fees from the UK Food Standards Agency (T07062). J. O'B. Hourihane has received research support from the European Union (FOOD-CT-2005-514000) and has received lecture fees from Danone, Nutricia, and Stallergenes. M. Kowalski has received travel support. F. de Blay has received research support from Stallergenes and Chiesi; has received consultancy fees from Stallergenes, ALK-Abelló, Mundipharma, and Novartis; has received participation fees from Stallergenes and ALK-Abelló; and is a board member for and has received consultancy fees from Stallergenes, Mundipharma, ALK-Abelló, and Novartis. N. G. Papadopoulos has received consultancy fees from Abbvie, Novartis, Menarini, Meda, ALK-Abelló, and GlaxoSmithKline; has received research support from Nestlé, Merck, and GlaxoSmithKline; and has received lecture fees from Novartis, Uriach, GlaxoSmithKline, Allergopharma, Stallergenes, and MSD; and has received payment for development of educational presentations from Abbvie, Sanofi, Menarini, and Meda. M. Clausen has received lecture fees from and has received travel support from GlaxoSmithKline. A. C. Knulst has received research support from the European Commission (EuroPrevall project FOOD-CT-2005-514000). G. Roberts has received research support from the European Commission (EuroPrevall project FOOD-CT-2005-514000) and has received consultancy fees from Danone. T. Popov has received research support from the European Commission (EuroPrevall project FOOD-CT-2005-514000). A. B. Sprikkelman has received research support from Nutricia Advanced Medical Nutrition Netherlands, AstraZeneca Netherlands, TEVA Netherlands, and GlaxoSmithKline Netherlands; is a board member for GlaxoSmithKline Netherlands; has received research support from Danone Research Netherlands, Nutricia Advanced Medical Nutrition Netherlands, ALK-Abelló Netherlands, Thermo Fisher Netherlands, Yakult Netherlands, MARFO Netherlands, GlaxoSmithKline Netherlands, Chiesi Netherlands, Stallergenes Netherlands, Medapharma Netherlands, and Allergy Therapeutics Netherlands; and has received lecture fees from Nutrica Advanced Medical Nutrition Netherlands. S. Vieths has received consultancy fees from the Food Allergy Resource and Research Program (Lincoln, Nebraska), the Institute for Product Quality (Berlin, Germany), and Fresenius Academy (Dortmund, Germany); has provided expert testimony for the Medical University of Vienna, Austria; has received research support from Monsanto Company and Pioneer Hi-Bred International; has received lecture fees from the AAAAI, Deutsche Dermatologische Gesellschaft, the Spanish Society of Allergy and Clinical Immunology, Westdeutsche Arbeitsgemeinschaft für pädiatrische Pneumologie und Allergologie e.V. (Köln, Germany), Gesellschaft für pädiatrische Allergologie und Umweltmedizin, and Ärzteverband Deutscher Allergologen; has received royalties from Schattauer Allergologie and Elsevier Nahrungsmittelaller-gien und IntoleranzenHandbuch; and has received travel support from the German Research Foundation, the Federal Institute for Risk Assessment, the Austrian Society for Allergology and Immunology, the French Society of Allergology, the European Directorate for the Quality of Medicines and Health Care, the EAACI, the World Allergy Organization, Technical University of Munich, Deutscher Allergie- und Asthmabund, Association Monégasque pour le Perfectionnement des Connaissances des Médicins, the Federal Office of Consumer Protection and Food Safety, the German Chemical Society (GDCh), the Austrian Society for Dermatology and Venerology, and AKM Allergiekongress. R. van Ree has received research support and travel support from the European Union (FOOD-CT-2005-514000, CT201871), is a board member for EAACI, and is employed by Academic Medical Center. R. Crevel is employed by and has stock/stock options in Unilever and has received royalties from Elsevier. E. N. C. Mills has received research support from the European Union (FOOD-CT-2005-514000), the Biological and Biotechnological Sciences Research Council (BBS/E/F/00041800, BBS/E/F/00042204), the UK Food Standards Agency (T07062), the European Food Safety Authority, the UK Technology Strategy Board (grant no. 101130), DBV Technology, and Novartis; is a board member for Novartis, the UK Food Standards Agency, PepsiCo International, the UK Biological and Biotechnological Sciences Research Council, and Reacta Biotech Ltd; is employed by the University of Manchester and the Institute of Food Research; has stock/stock options in Standard Life and Reacta Biotech; has received travel support from ILSI, EAACI, the University of Bologna, Europa Bio, the British High Commission, the Iceland Allergy Society, Fresenius, EuroFood Tox 2013, and the IUNS Annual Meeting (Granada, Spain September 2013); and was paid as a lecturer and supervisor of masters students at Imperial College and as an external examiner at the University of Birmingham. The rest of the authors declare that they have no relevant conflicts of interest. |
© 2014
American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
Vol 135 - N° 4
P. 964-971 - avril 2015 Retour au numéro
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