Skip to main content

Oral Food Challenges: The Design must Reflect the Clinical Question

Current Allergy and Asthma Reports volume 15, Article number: 51 (2015) Cite this article

Abstract

Oral food challenges are the gold-standard diagnostic investigation for diagnosing food allergy. They allow a subject to consume an age-appropriate portion of allergenic food under surveillance to assess whether a reproducible immune-mediated adverse response is demonstrated. The specific design of food challenge must closely reflect the anticipated management step being considered. In clinical practice, food challenges are most commonly used to investigate the subject’s status of allergy or tolerance to a food. However, other characteristics of food allergy are increasingly being investigated through recent studies. In particular, studies investigating food allergy prevention strategies, the impact of oral immunotherapy on subjects’ threshold for allergic reactions and also their potential acquisition of long-term tolerance each utilize differing designs of oral food challenges to investigate their specific hypothesis. We examine how oral food challenges may be designed to assess specific characteristics of the food allergic response.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID- sponsored expert panel. J Allergy Clin Immunol. 2010;126:S1–58.

    PubMed Central  PubMed  Article  Google Scholar 

  2. Sampson HA, van Wijk RG, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, et al. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology–European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012;130:1260–74. This consensus report by food allergy experts from EAACI and AAAAI on the conduct and interpretation of DBPCFCs sets out to develop a standardized approach for DBPCFCs in research. While more recent studies highlight important design variables not fully explored in this publication, it provides a valuable guide for developing robust DBPCFC designs.

    PubMed  Article  Google Scholar 

  3. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014;69:1008–25.

    CAS  PubMed  Article  Google Scholar 

  4. Nowak-Wegrzyn A, Assa’ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS. Work Group report: oral food challenge testing. J Allergy Clin Immunol. 2009;123(6):S365–83.

    PubMed  Article  Google Scholar 

  5. Anagnostou K, Stiefel G, Brough H, du Toit G, Lack G, Fox A. Active management of food allergy: an emerging concept. Arch Dis Child. 2014;100(4):386–90. This review examines new approaches to allergy management based on emerging research including: early introduction of potentially allergenic foods, anticipatory testing, active monitoring, desensitisation to food allergens and active risk management.

    PubMed  Article  Google Scholar 

  6. Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803–13. The first study to show that peanut allergy can be prevented, this noteworthy study compares peanut consumption and avoidance as strategies to prevent peanut allergy in a high risk population. OFCs are key to evaluate the primary outcome of peanut allergy or tolerance.

    PubMed  Article  Google Scholar 

  7. Marrs T, du Toit G, Fox AT, Perkin MR, Lack G. Double-blind food challenges can be conducted effectively by using interspersed active and placebo doses among children. J Allergy Clin Immunol. 2013;132(2):502.

    PubMed  Article  Google Scholar 

  8. Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M, et al. Double-blind, placebo- controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol. 1988;82(6):986–97.

    CAS  PubMed  Article  Google Scholar 

  9. Vlieg-Boerstra BJ, Bijleveld CM, van Der HS, Beusekamp BJ, Wolt-Plompen SA, Kukler J, et al. Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children. J Allergy Clin Immunol. 2004;113(2):341–6.

    PubMed  Article  Google Scholar 

  10. Grimshaw KE, King RM, Nordlee JA, Hefle SL, Warner JO, Hourihane JO. Presentation of allergen in different food preparations affects the nature of the allergic reaction—a case series. Clin Exp Allergy. 2003;33(11):1581–5.

    CAS  PubMed  Article  Google Scholar 

  11. Taylor SL, Baumert JL, Kruizinga AG, Remington BC, Crevel RW, Brooke-Taylor S, et al. Establishment of reference doses for residues of allergenic foods: report of the VITAL expert panel. Food Chem Toxicol. 2014;63:9–17.

    CAS  PubMed  Article  Google Scholar 

  12. Ballmer-Weber BK, Fernandez-Rivas M, Beyer K, Defernez M, Sperrin M, Mackie AR, et al. How much is too much? Threshold dose distributions for 5 allergens. J Allergy Clin Immunol. 2015;135(4):964–71.

    CAS  PubMed  Article  Google Scholar 

  13. Sicherer SH, Morrow EH, Sampson HA. Dose response in double-blind, placebo-controlled oral food challenges in children with atopic dermatitis. J Allergy Clin Immunol. 2000;105:582–6.

    CAS  PubMed  Article  Google Scholar 

  14. Torr T, Gaughan M, Roberts G, Bynoe Y, Semple E, Lack G, et al. Food challenges: a review and audit. Paediatr Nurs. 2002;14(9):30–4.

    PubMed  Article  Google Scholar 

  15. Narisety SD, Skripak JM, Steele P, Hamilton RG, Matsui EC, Burks AW, et al. Open-label maintenance after milk oral immunotherapy for IgE-mediated cow’s milk allergy. J Allergy Clin Immunol. 2009;124(3):610–2.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  16. Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, Gorelik M, Schroeder J, et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol. 2015;135(5):1275–82.

  17. Anagnostou K, Clark A, King Y, Islam S, Deighton J, Ewan P. Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome. Clin Exp Allergy. 2011;41:1273–81.

    CAS  PubMed  Article  Google Scholar 

  18. Blumchen K, Ulbricht H, Staden U, Dobberstein K, Beschorner J, Camargo Lopes de Oliveira L, et al. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol. 2010;126:83–91.

    CAS  PubMed  Article  Google Scholar 

  19. Zhu J, Pouillot R, Kwegyir-Afful EK, Luccioli S, Gendel SM. A retrospective analysis of allergic reaction severity and minimal eliciting doses for peanut, milk, egg, and soy oral food challenges. Food Chem Toxicol. 2015;80:92–100. This retrospective analysis of published data from OFCs assesses the relationship between reaction severities and minimal eliciting doses. The relationship between threshold dose distribution and reaction severity was different for peanut compared with other food allergens. Peanut allergic patients who had severe reactions had higher minimal eliciting doses than those who had mild and moderate reactions. There were no significant differences in threshold dose distributions and reaction severity for the other foods tested.

  20. Syed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133(2):500–10. This peanut OIT trial investigates the specific immune mechanisms associated with development of clinical tolerance. Sustained unresponsiveness is assessed at 3 and 6 months after stopping treatment. The supplementary material contains a detailed overview of OFC design and a detailed summary of participant allergy assessments and OFC outcomes at screening and second sustained unresponsiveness challenge.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  21. Burks WA et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367:233–43.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  22. Vickery BP, Scurlock AM, Kulis M, Steele PH, Kamilaris J, Berglund JP, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol. 2014;133:468–75. This study was the first to demonstrate sustained unresponsiveness after peanut OIT. The use of high maintenance doses and long treatment duration is novel in this field. Compared to other OIT studies, DBPCFCs in this study use higher cumulative doses to assess desensitization and sustained unresponsiveness.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  23. Tang M, Ponsonby AL, Orsini F, Tey D, et al. Administration of a probiotic with peanut oral immunotherapy: a randomized trial. J Allergy Clin Immunol. 2015;135(3):737–44.

    CAS  PubMed  Article  Google Scholar 

  24. Marrs T, Flohr C, Perkin MR. Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a critical appraisal. Br J Dermatol. In press.

  25. Varshney P, Jones SM, Scurlock AM, Perry TT, et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011;127:654–60.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  26. Strid J, Thomson M, Hourihane J, Kimber I, Strobel S. A novel model of sensitization and oral tolerance to peanut protein. Immunology. 2004;113(3):293–303.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  27. Anagnostou K, Islam S, King Y, Foley L, et al. Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. Lancet. 2014;383(9925):1297–304. This randomized controlled phase 2 crossover study establishes the efficacy of OIT for the desensitization of children with peanut allergy.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  28. Jones SM, Pons L, Roberts JL, Scurlock AM, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124:292–300.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  29. Blumchen K, Beder A, Beschorner J, Ahrens F, et al. Modified oral food challenge used with sensitization biomarkers provides more real-life clinical thresholds for peanut allergy. J Allergy Clin Immunol. 2014;134:390–8.

    CAS  PubMed  Article  Google Scholar 

  30. Pettersson ME, de Blok BMJ F, van Der Heide S, Kukler J, Dubois AEJ. Is 30 minutes between doses long enough in oral food challenges? Pediatric Allergy and Immunology. 2014;25:600–19.

    Google Scholar 

  31. Maleki SJ, Chung SY, Champagne ET, Raufman JP. The effects of roasting on the allergenic properties of peanut proteins. J Allergy Clin Immunol. 2000;106:763–8.

    CAS  PubMed  Article  Google Scholar 

  32. Beyer K, Morrow E, Li XM, Bardina L, Bannon GA, Burks AW. Effects of cooking methods on peanut allergenicity. J Allergy Clin Immunol. 2001;107(6):1077–81.

    CAS  PubMed  Article  Google Scholar 

  33. Bloom KA, Huang FR, Bencharitiwong R, Bardina L, Ross A, Sampson HA, et al. Effect of heat treatment on milk and egg proteins allergenicity. Pediatr Allergy Immunol. 2014;2598:740–6.

    Article  Google Scholar 

  34. Libbers L, Flokstra-de Blok BMJ, Vlieg-Boerstra BJ, Van der Heide S, van der Muelen GN, Kukler J, et al. No matrix effect in double-blind, placebo-controlled egg challenges in egg allergic children. Clin Exp Allergy. 2013;43:1067–70.

    CAS  PubMed  Article  Google Scholar 

  35. Brockow K, Kniessl D, Valentini L, Zelger O, Grosber L et al. Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis. J Allergy Clinical Immunol. 2015 (In press) This study investigates the effects of acetylsalicyclic acid and alcohol as cofactors in WDEIA. They use high doses of pure gluten-flour bread (delivering higher doses of wheat protein than used in other wheat challenge protocols) to overcome nonresponsiveness which often occurs in diagnostic OFCs followed by exercise. They found that exercise is not an essential trigger for onset of symptoms in WDEIA.

  36. Koplin JJ, Tang ML, Martin PE, Osborne NJ, Lowe AJ, et al. Predetermined challenge eligibility and cessation criteria for oral food challenges in the HealthNuts population-based study of infants. J Allergy Clin Immunol. 2012;129(4):1145–7.

    PubMed  Article  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Mary Feeney and George du Toit declare grants from National Institute of Allergy and Infectious Diseases (NIAID, NIH) and UK Food Standards Agency (FSA) and other support from Food Allergy Research & Education, MRC & Asthma UK Centre, UK Dept of Health through NIHR, National Peanut Board (NPB) and Osem. Gideon Lack reports grants from National Institute of Allergy and Infectious Diseases (NIAID, NIH) and UK Food Standards Agency (FSA), support from Food Allergy Research & Education, MRC & Asthma UK Centre, UK Dept of Health through NIHR, National Peanut Board (NPB), Osem and personal fees from DBV Technologies.

Dr. Tom Marrs reports working within project grants from British Skin Foundation Charity, and from MRC and Food Standards Agency funding, with salary funding derived from Medical and Dental Educational Levy (Madel) through KCL MRC Asthma UK Centre , and previously from NIHR, with additional consultancy fees from Imperial College London, outside this submitted work.

Human and Animal Rights and Informed Consent

Informed written consent was obtained for all LEAP Study participants from their parent or guardian.

Author information

Affiliations

  1. Department of Paediatric Allergy, Division of Asthma, Allergy and Lung Biology, King’s College London and Guy’s and St Thomas’ National Health Service Foundation Trust, Westminster Bridge Road, London, SE1 7EH, UK

    Mary Feeney, Tom Marrs, Gideon Lack & George Du Toit

Authors
  1. Mary Feeney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tom Marrs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gideon Lack
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George Du Toit
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Du Toit.

Additional information

Mary Feeney and Tom Marrs are co-first authors on this work.

This article is part of the Topical Collection on Food Allergy

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Feeney, M., Marrs, T., Lack, G. et al. Oral Food Challenges: The Design must Reflect the Clinical Question. Curr Allergy Asthma Rep 15, 51 (2015). https://doi.org/10.1007/s11882-015-0549-6

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-015-0549-6

Keywords

  • Oral food challenge
  • Double blind placebo controlled food challenge
  • Food allergy
  • Allergy prevention
  • Oral immunotherapy