Analysis of a large standardized food challenge data set to determine predictors of positive outcome across multiple allergens

Sayantani Sindher, Andrew J. Long, Natasha Purington, Madeleine Chollet, Sara Slatkin, Sandra Andorf, Dana Tupa, Divya Kumar, Margaret A. Woch, Katherine L. O'Laughlin, Amal Assaad, Jacqueline A Pongracic, Jonathan M. Spergel, Jonathan Tam, Stephen Tilles, Julie Wang, Stephen J. Galli, Kari C. Nadeau, R. Sharon Chinthrajah*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number2689
JournalFrontiers in immunology
Volume9
Issue numberNOV
DOIs
StatePublished - Nov 27 2018

Keywords

  • AUC
  • Biomarker evaluation
  • Cumulative tolerated dose
  • Food challenge
  • Time-dependent ROC

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sindher, S., Long, A. J., Purington, N., Chollet, M., Slatkin, S., Andorf, S., Tupa, D., Kumar, D., Woch, M. A., O'Laughlin, K. L., Assaad, A., Pongracic, J. A., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Galli, S. J., Nadeau, K. C., & Chinthrajah, R. S. (2018). Analysis of a large standardized food challenge data set to determine predictors of positive outcome across multiple allergens. Frontiers in immunology, 9(NOV), [2689]. https://doi.org/10.3389/fimmu.2018.02689