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Risk prediction of severe reaction to oral challenge test of cow’s milk

  • Original Article
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Abstract

Cow’s milk is one of the most common food allergens among children. Oral food challenge tests determine the threshold dose of allergens, but have not been standardized. To reduce the severe reactions, we developed a practical model of the test. We studied 111 high-risk patients who underwent a first milk oral food challenge on the risk-stratified dose between 2011 and 2017 for predicting the severe reaction risk. Severe reactions were defined as showing > 3 of Sampson’s classification grade. Twenty-eight patients (25%) showed severe reactions without death. Prior to oral food challenge, severe reaction patients experienced milk avoidance (71% vs. 45%, p = 0.02) or bronchial asthma (61% vs. 28%, p = 0.003) more frequently and showed higher milk-specific IgE levels (median 28.3 vs. 7.7 UA/mL, p < 0.0001) than non-severe reaction patients. Multivariate logistic regression analyses established a formula including severe reaction-associated factors; increased levels of milk-specific IgE (odds ratio 11.61, p = 0.001), milk avoidance (odds ratio 3.88, p = 0.02), and bronchial asthma (odds ratio 3.75, p = 0.02). This model had 86% sensitivity and 56% specificity (cut-off 0.25) for risk. Five patients with < 25% probability developed severe reactions, which started in > 3 grade dyspnea up to 20 mL of challenge.

Conclusion: This model could effectively reduce the severe reaction development on the first milk oral food challenge test according to the individual needs.

What is Known:

•Higher levels of milk-specific IgE values, bronchial asthma, and complete milk avoidance are independent risk factors of severe reactions during the cow’s milk oral food challenge.

What is New:

•Statistical analyses of our milk oral food challenge records for 111 patients helped us develop a model formula predicting severe reactions at the first test with high specificity and sensitivity.

•This simple risk-stratified protocol is useful for minimizing the adverse events in the first milk challenge.

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Abbreviations

AUC:

Area under the curve

CM:

Cow’s milk

IgE:

Immunoglobulin E

OFC:

Oral food challenge

OR:

Odds ratio

ROC:

Receiver operating characteristics

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Acknowledgments

We thank all members of the specialized team for supporting the completion of the OFC tests at Fukuoka Higashi Medical Center and Fukuoka Children’s Hospital. We also thank Dr. Brian Quinn (Editor-in-Chief. Japan Medical Communication) for editing the manuscript.

Funding

This work was supported in part by a Grant-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant from the Ministry of Health, Labor and Welfare of Japan.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Takahiro Kawahara & Shouichi Ohga

  2. Division of Pediatrics, National Hospital Organization Fukuoka Higashi Medical Center, 1-1-1 Chidori, Koga city, Fukuoka, 811-3195, Japan

    Takahiro Kawahara, Natsuko Masumoto & Makiko Nanishi

  3. Division of Allergy and Pulmonology, Fukuoka Children’s Hospital, 5-1-1 Kashiiteriha, Higashi-ku, Fukuoka, 813-0017, Japan

    Junichiro Tezuka

  4. Division of Pediatrics, National Hospital Organization Fukuoka Hospital, 1-39-1 Yakatabaru Minami-ku, Fukuoka, 811-1394, Japan

    Takahito Ninomiya & Satoshi Honjo

  5. Division of Pediatrics, National Hospital Organization Kyushu Cancer Center, 1-1-3 Nodame Minami-ku, Fukuoka, 811-1395, Japan

    Hideki Nakayama

Authors
  1. Takahiro Kawahara
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  2. Junichiro Tezuka
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  8. Shouichi Ohga
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Contributions

Takahiro Kawahara, Junichiro Tezuka, and Shouichi Ohga were the principal investigators taking primary responsibility for the paper. Natsuko Masumoto and Makiko Nanishi completed the survey questionnaires, made the clinical diagnosis, and confirmed the clinical and laboratory data. Takahito Ninomiya and Hideki Nakayama supported the clinical study with helpful discussions. Satoshi Honjo supported the statistical analysis. Takahiro Kawahara and Junichiro Tezuka wrote the first draft of the manuscript.

Corresponding author

Correspondence to Junichiro Tezuka.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This investigation was approved by the Institutional Review Board at the institutions (Registration code: H29-clini2). This article does not contain any studies with animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Communicated by Nicole Ritz

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Kawahara, T., Tezuka, J., Ninomiya, T. et al. Risk prediction of severe reaction to oral challenge test of cow’s milk. Eur J Pediatr 178, 181–188 (2019). https://doi.org/10.1007/s00431-018-3274-z

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  • DOI: https://doi.org/10.1007/s00431-018-3274-z

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