Anaphylaxis, drug allergy, urticaria, and angioedema
Cardiovascular changes during peanut-induced allergic reactions in human subjects

https://doi.org/10.1016/j.jaci.2020.06.033Get rights and content
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Background

Food allergy is the most common cause of anaphylaxis. Changes in posture during acute reactions can trigger fatal outcomes, but the impact of allergic reactions on the cardiovascular system in nonfatal reactions remains poorly understood.

Objective

Our aim was to systematically evaluate changes in cardiovascular function during acute allergic reactions to peanut.

Methods

Participants underwent double-blind placebo-controlled food challenge to peanut as part of a clinical trial. Changes in hemodynamic parameters (heart rate, stroke volume, blood pressure, and peripheral blood flow) and electrocardiogram findings during food challenges were assessed using noninvasive continuous monitoring.

Results

A total of 57 adults (median age 24 years [interquartile range = 20-29]), 53% of whom were female, participated; 22 (39%) had anaphylaxis. Acute reactions were associated with significant changes in stroke volume (mean decrease of 4.2% [95% CI = 0.8-7.6; P = .03]), heart rate (mean increase 11.6% [95% CI = 8.4-14.8; P < .0001]), and peripheral blood flow (mean increase 19.7% [95% CI = 10.8-28.6; P < .0001]), irrespective of reaction severity. These changes were reproduced at a subsequent repeat peanut challenge in 26 participants, and could be reversed with administration of intravenous fluids which resulted in faster resolution of abdominal symptoms.

Conclusions

In this first detailed human study of cardiovascular changes during food-induced allergic reactions, we found evidence for significant fluid redistribution, independent of reaction severity. This provides a sound rationale for optimizing venous return during significant allergic reactions to food. Finally, these data provide a new paradigm for understanding severity in anaphylaxis, in which poor outcomes may occur as a result of a failure in compensatory mechanisms.

Key words

Anaphylaxis
cardiac output
cardiovascular
food allergens
intravenous fluids
management
stroke volume
venous return

Abbreviations used

BP
Blood pressure
CO
Cardiac output
DBPCFC
Double-blind placebo-controlled food challenge
HR
Heart rate
HRV
Heart rate variability
IQR
Interquartile range
OCR
Objective clinical reaction
SV
Stroke volume
VAS
Visual analog scale

Cited by (0)

Funding: This research was funded by a UK Medical Research Council Clinician Scientist award to P.J.T. (reference MR/K010468/1). Clinical challenges in the TRACE study were funded by the UK Food Standards Agency, with additional support for follow-up challenges through the European Union’s Seventh Framework Program for Research, Technological Development, and Demonstration under grant agreement no. 312147 (Integrated Approaches to Food Allergen and Allergy Risk Management [chief investigator, Clare Mills) and the National Institute for Health Research Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure of potential conflict of interest: M. H. Shamji has received grants from ALK-Abelló, Regeneron, Merck, ASIT Biotech.sa, and the Immune Tolerance Network and has received personal fees from ASIT Biotech.sa, ALK-Abelló, Allergopharma, and UCB. E. N. C. Mills has received grant support from the UK Biological and Biotechnological Sciences Research Council, DBV Technologies, Reacta Biotech, the Medical Research Council, the European Union, and the UK Food Standards Agency and has patents pending to Reacta Biotech Ltd (PCT/GB2016/051637 and PCT/GB2016/053829). A. R. Lyon has received speaker, advisory board, or consultancy fees and/or research grants from Pfizer, Novartis, Servier, Amgen, Takeda, Roche, Janssens-Cilag Ltd., Clinigen Group, Eli Lily, Eisai, Bristol-Myers Squibb, Ferring Pharmaceuticals, and Boehringer Ingelheim. S. R. Durham receives grant support from the Immune Tolerance Network, National Institute of Allergy and Infectious Diseases, ALK-Abelló, Regeneron, and Biotech Tools and serves as a consultant from Anergis, Circassia, Biomay, Merck, Allergy Therapeutics, Med Update GmbH, and Food Standards Agency. P. J. Turner reports grants from UK Medical Research Council, National Institute for Health Research/Imperial BRC and JM Charitable Foundation during the conduct of the study, as well as personal fees from UK Food Standards Agency and DBV Technologies, personal fees and nonfinancial support from Aimmune Therapeutics, other support from Allergenis, and personal fees from ILSI Europe, outside the submitted work. R. J. Boyle has received honoraria for participating in advisory boards for ALK-Abelló, Prota Therapeutics, and DBV Technologies and consultancy payment for designing a clinical trial for the Dairy Goat Cooperative; in addition, he has given expert testimony in cases relating to food anaphylaxis and infant formula health claims. The rest of the authors declare that they have no relevant conflicts of interest.

Monica Ruiz-Garcia, MD, PhD is now employed by Laboratorios Leti; her employment by Laboratorios Leti did not begin until after the present study's data lock and completion of its analyses.

These authors are joint senior authors.