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Front. Immunol. | doi: 10.3389/fimmu.2018.02689

Analysis of a Large Standardized Food Challenge Data Set to Determine Predictors of Positive Outcome Across Multiple Allergens

 Sayantani Sindher1,  Andrew J. Long1,  Natasha Purington1, Madeleine Chollet1, Sara Slatkin1,  Sandra Andorf1, Dana Tupa1, Divya Kumar1, Margaret A. Woch1,  Katherine L. O'Laughlin1,  Amal Assaad2, Jacqueline Pongracic3,  Jonathan Spergel4,  Jonathan Tam5, Stephen Tilles6, Julie Wang7,  Stephen J. Galli1,  Kari C. Nadeau1 and  R. Sharon Chinthrajah1*
  • 1Stanford University, United States
  • 2Cincinnati Children's Hospital Medical Center, United States
  • 3Ann & Robert H. Lurie Children's Hospital of Chicago, United States
  • 4Perelman School of Medicine, University of Pennsylvania, United States
  • 5Children's Hospital of Los Angeles, United States
  • 6Northwest Asthma and Allergy Center, University of Washington, United States
  • 7Icahn School of Medicine at Mount Sinai, United States

Background. Double-blind placebo-controlled food challenges (DBPCFCs) remain the gold standard for the diagnosis of food allergy; however, challenges require significant time and resources and place the patient at an increased risk for severe allergic adverse events. There have been continued efforts to identify alternative diagnostic methods to replace or minimize the need for oral food challenges (OFCs) in the diagnosis of food allergy.

Methods. Data was extracted for all IRB-approved, Stanford-initiated clinical protocols involving standardized screening OFCs to a cumulative dose of 500 mg protein to any of 11 food allergens in participants with elevated skin prick test (SPT) and/or specific IgE (sIgE) values to the challenged food across 7 sites. Baseline population characteristics, biomarkers, and challenge outcomes were analyzed to develop diagnostic criteria predictive of positive OFCs across multiple allergens in our multi-allergic cohorts.

Results. A total of 1247 OFCs completed by 427 participants were analyzed in this cohort. Eighty-five percent of all OFCs had positive challenges. A history of atopic dermatitis and multiple food allergies were significantly associated with a higher risk of positive OFCs. The majority of food-specific SPT, sIgE, and sIgE/total IgE (tIgE) thresholds calculated from cumulative tolerated dose (CTD)-dependent receiver operator curves (ROC) had high discrimination of OFC outcome (area under the curves > 0.75). Participants with values above the thresholds were more likely to have positive challenges.

Conclusions. This is the first study to our knowledge, to not only adjust for tolerated allergen dose in predicting OFC outcome, but to also use this method to establish biomarker thresholds. The presented findings suggest that readily obtainable biomarker values and patient demographics may be of use in the prediction of OFC outcome and food allergy. In the subset of patients with SPT or sIgE values above the thresholds, values appear highly predictive of a positive OFC and true food allergy. While these values are relatively high, they may serve as an appropriate substitute for food challenges in clinical and research settings.

Keywords: Food challenge, Cumulative tolerated dose, AUC, Biomarker evaluation, Time-dependent ROC

Received: 03 Jul 2018; Accepted: 31 Oct 2018.

Edited by:

Vida Abedi, Geisinger Health System, United States

Reviewed by:

Nicolò Merendino, Università degli Studi della Tuscia, Italy
Xi Ma, China Agricultural University, China  

Copyright: © 2018 Sindher, Long, Purington, Chollet, Slatkin, Andorf, Tupa, Kumar, Woch, O'Laughlin, Assaad, Pongracic, Spergel, Tam, Tilles, Wang, Galli, Nadeau and Chinthrajah. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. R. Sharon Chinthrajah, Stanford University, Stanford, 94305, California, United States,