title: How much is too much? Threshold dose distributions for 5 food allergens.
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.
  
  
  CONCLUSIONS
  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.affiliation: Allergy Unit, Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Ballmer-Weber
authors.affiliation: Allergy Department, Hospital Clinico San Carlos, IdISSC, Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fernandez-Rivas
authors.affiliation: Department of Paediatric Pneumology and Immunology, Charité University Medical Center, Berlin, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Beyer
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom.
authors.forename: Marianne
authors.initials: M
authors.lastname: Defernez
authors.affiliation: Institute of Population Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sperrin
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Mackie
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Salt
authors.affiliation: University College Cork, Cork, Ireland.
authors.forename: Jonathan O'B
authors.initials: JO
authors.lastname: Hourihane
authors.affiliation: Ambulatorio di Allergologia, Clinica San Carlo, Paderno-Dugnano, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Asero
authors.affiliation: Faculty Hospital Bulovka, Department of Pediatrics, Prague, Czech Republic.
authors.forename: Simona
authors.initials: S
authors.lastname: Belohlavkova
authors.affiliation: Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kowalski
authors.affiliation: Chest Disease Department, University Hospital, Federation of Translational Medicine, University of Strasbourg, Strasbourg, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: de Blay
authors.affiliation: Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Papadopoulos
authors.affiliation: Children's Hospital Iceland, Landspitali, University Hospital, Reykjavik, Iceland.
authors.forename: Michael
authors.initials: M
authors.lastname: Clausen
authors.affiliation: University Medical Center Utrecht, Department of Dermatology/Allergology, Utrecht, The Netherlands.
authors.forename: André C
authors.initials: AC
authors.lastname: Knulst
authors.affiliation: Human Development and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Roberts
authors.affiliation: Medical University, Clinical Centre of Allergology of the Alexandrovska Hospital, Sofia, Bulgaria.
authors.forename: Ted
authors.initials: T
authors.lastname: Popov
authors.affiliation: Department of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Aline B
authors.initials: AB
authors.lastname: Sprikkelman
authors.affiliation: Chest Clinics, Allergology and Radiology, Medical Faculty, Vilnius University, Vilnius, Lithuania.
authors.forename: Ruta
authors.initials: R
authors.lastname: Dubakiene
authors.affiliation: Paul Ehrlich Institute, Langen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vieths
authors.affiliation: Department of Experimental Immunology and Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Ree
authors.affiliation: Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, United Kingdom.
authors.forename: René
authors.initials: R
authors.lastname: Crevel
authors.affiliation: 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.
authors.forename: E N Clare
authors.initials: ENC
authors.lastname: Mills
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D002648:Child; D005060:Europe / Q000453:epidemiology; D005502:Food / Q000009:adverse effects; D005512:Food Hypersensitivity / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000276:immunology; D011159:Population Surveillance; D015995:Prevalence; D063189:Symptom Assessment; D055815:Young Adult
chemical_list: D000485:Allergens; D007073:Immunoglobulin E
keywords: EuroPrevall; Food; allergy; celeriac; fish; hazelnut; peanut; shrimp; threshold