MICA: Identifying risks for severe life-threatening allergic reactions to foods (IRIS-Allergy)

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

Food allergy affects up to 3% of adults and 6% of children in the UK, and causes serious reactions (anaphylaxis) which can be fatal. Key to management is dietary avoidance; despite this, accidental reactions are common. Food-allergic patients are therefore prescribed rescue medication (such as adrenaline auto-injectors) to treat anaphylaxis. Most allergic reactions are not life-threatening, and respond to rescue medication. However, very severe reactions do occur and can cause death, even if adrenaline is injected in a timely manner.

Currently, we are unable to identify patients at greatest risk of severe reactions. This has a significant adverse impact on quality of life, since all food-allergic individuals must be considered as being at risk of life-threatening reactions. As a result, food-allergic patients, their family and carers, food businesses and regulatory authorities have to prioritise safety and take a maximum risk-averse approach to management - creating a major public health issue.

In this project, we will address a key question: can we explain why some food-allergic individuals have near-fatal reactions or die from anaphylaxis, whereas the majority will never have a truly life-threatening reaction despite multiple food exposures and reactions during their lifetime?

Our group has discovered that most food-allergic patients have a similar pattern of 'stereotypical' symptoms if exposed to the food they are allergic to on multiple occasions at in-hospital food challenges. For example, some always suffer abdominal pain, whilst others do not experience gut symptoms but present with anaphylaxis. This also seems to be the case for reactions due to accidental exposure happening in the community. Furthermore, the severity of symptoms at food challenge do not correlate well to the amount of allergen eaten. These data suggest that some patients have a predisposition towards very severe (and fatal) anaphylaxis - for example, an inability to compensate when they have an allergic reaction. This represents a new paradigm in understanding factors which contribute to severe outcomes in anaphylaxis, and suggests that fatal/near-fatal food-anaphylaxis could be considered an orphan disease.

Our hypothesis is that patients with truly life-threatening anaphylaxis have a different response to food allergen, which can be identified and used to predict risk. The infrastructure of the NHS provides a unique opportunity for us to investigate this.

PROJECT PLAN
Using NHS datasets, and in full compliance with data protection legislation, we will identify food-allergic individuals who have experienced a previous life-threatening reaction requiring intensive care in an NHS hospital in England ("cases"). We will also recruit patients who experienced a less severe anaphylaxis reaction to the same allergen around the same time, as "controls".

Both "cases" and controls will be invited to attend for a detailed assessment, which will include a thorough interview to assess the circumstances of their food allergic reaction(s), and their tendency to asthma and its severity (which could increase the risk of severe reactions). We will complete immune profiling of their allergies using novel chip-based technologies. Anaphylaxis is caused by the activation of "effector" cells such as mast cells and basophils. We will investigate whether differences in anaphylaxis severity can be linked to differences in reactivity of these "effector" cells in the skin and blood. We will also collect samples for future genetic analyses to assess for traits which might predispose towards more severe reactions.

By undertaking this evaluation, we will be able to compare cases to controls, to define the circumstances of near-fatal anaphylaxis reactions to food, and identify risk factors for severe outcomes.

Our longer-term aim is to develop a risk calculator which can be used by clinicians to identify those at greatest risk of potentially fatal reactions.

Technical Summary

OBJECTIVES
Undertake a case-control study to assess potential risk factors for near-fatal food anaphylaxis, and evaluate whether specific host factors (IgE sensitisation, effector cell regulation) predispose to more severe reactions.

METHODS
i) CASE IDENTIFICATION: using linked NHS data with appropriate ICD codes, we will identify all anaphylaxis admissions requiring Level 3 critical care (advanced respiratory support/multi-organ failure) in an NHS facility since 2008. This avoids any ambiguity in terms of determining "severity", while use of a national dataset minimises potential for selection bias. Control patients will be identified through a similar data search relating to anaphylaxis presentations to hospital (irrespective of reaction severity, but not requiring intensive care) within a similar time window and matching for age/sex.

ii) CASE VERIFICATION: Under section 251 exemption and with ethics approval, potential participants will be invited to provide information regarding the circumstances of their anaphylaxis event; causality will be determined through clinical history and allergy testing. Where possible, these details will be verified against medical notes and prescription records.

iii) CASE INVESTIGATION: Participants will be invited to undergo the following assessments: lung function/bronchial hyperreactivity; immunological (in vivo and in vitro IgE sensitisation including epitope reactivity; mast cell and basophil activation/degranulation).

OUTPUTS:
Case-control comparison to evaluate risk factors for severity, including asthma; IgE sensitisation; other co-morbidities and co-factors. We will also undertake unsupervised data-driven analyses using functional data analysis clustering and predictive models to assess clinical/physiological/genetic/immune factors which might predict risk and be used to develop a risk-prediction model.

Publications

10 25 50

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Arasi S (2023) WAO consensus on DEfinition of Food Allergy SEverity (DEFASE). in The World Allergy Organization journal

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Bartra J (2023) Cofactors in food anaphylaxis in adults. in Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

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Dribin TE (2023) Who Needs Epinephrine? Anaphylaxis, Autoinjectors, and Parachutes. in The journal of allergy and clinical immunology. In practice

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Foong RX (2023) Preventing food allergy fatalities. in Archives of disease in childhood

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Gowland M (2024) Encyclopedia of Food Allergy

 
Description Expert Participant in a workshop by ACNFP to evaluate risk assessment for novel food proteins
Geographic Reach Europe 
Policy Influence Type Participation in a guidance/advisory committee
URL https://acnfp.food.gov.uk/ACNFPNovelFoodAssessments
 
Description Expert to FSA on Precautionary Allergen Labelling
Geographic Reach National 
Policy Influence Type Contribution to a national consultation/review
 
Description Informing the care of allergic teenagers in UK
Geographic Reach National 
Policy Influence Type Contribution to new or improved professional practice
Impact Asked to advise on national service specifications for "allergy" through NHS England, and specifically to inform transitioning of care of children into adult services. Once adopted by NHS England, the service specs will become the key set of standards to inform specialist commissioning in the NHS.
 
Description Management of anaphylaxis in vaccination setting
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Specifically, review the need for oxygen and other adjuncts in managing faints/collapse occurring in the vaccination setting.
URL https://www.gov.uk/government/publications/vaccine-safety-and-adverse-events-following-immunisation-...
 
Description New UK guideline on perioperative anaphylaxis (through RCUK)
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
URL https://www.resus.org.uk/sites/default/files/2024-01/2526%20AAP%20RCUK%20periop%20anaphylaxis-8C.pdf
 
Title Non-injectable adrenaline 
Description Asked to provide expert input to a number of pharma companies developing alternatives to injectable adrenaline for the treatment of acute allergic reactions and anaphylaxis. Aim is to overcome some of the existing barriers to optimal treatment of anaphylaxis, including needle-phobia, cost of treatment. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Market authorisation
Year Development Stage Completed 2025
Development Status Under active development/distribution
Impact Ongoing work under development. 
 
Description Anaphylaxis UK Business Supporters Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Speaker at a one-day supporters seminar for Anaphylaxis UK, a leading patient charity.
Year(s) Of Engagement Activity 2023
URL https://www.anaphylaxis.org.uk/business/symposium/
 
Description BBC World Service The Evidence on allergies 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact 90min seminar recorded at Wellcome Institute for BBC World Service on questions such as:
- Is the world becoming more allergic?
- What are allergies and what is the purpose of them?
- They are increasingly common in towns and cities but are they still on the rise?
- Are we close to finding any cures?
Year(s) Of Engagement Activity 2023
URL https://www.bbc.co.uk/programmes/w3ct5l4j
 
Description EFA meetings 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Multiple meetings with EFA, the European Federation of Allergy and Airways Diseases, a European alliance of 39 patient support groups. The interactions were specifically focussed on accurate diagnosis of food allergy and in particular, determination of reaction thresholds to inform allergen risk management.
Year(s) Of Engagement Activity 2023,2024
URL https://www.efanet.org
 
Description Improving cabin crew environment for passengers with food allergy / CAA 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Working group established by myself and leading representatives from Key Air Passenger carriers and CAA to improve policies related to helping food-allergic individuals and their caregivers feel safe when travelling by air. Monthly meetings to draw up national guidance which can then be implemented by airlines.
Year(s) Of Engagement Activity 2024,2025
URL https://www.caa.co.uk/passengers-and-public/
 
Description Interview for BBC radio 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact 30min radio podcast about transitioning of children with allergic diseases into adult services, for Radio 4.
Year(s) Of Engagement Activity 2025
URL https://www.bbc.co.uk/programmes/m00289nw
 
Description National Allergy Strategy Group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Appointed as vice chair to the National Allergy Strategy Group, an alliance of the professional organisation BSACI (British Society of Allergy and Clinical Immunology), the patient charities, Allergy UK, Anaphylaxis UK and Natasha Allergy Research Foundation. Since its formation in 2001, the NASG has worked, with others, to highlight the need for allergy services; the inadequate care available for allergy patients at all levels in the NHS and to improve NHS allergy services. The NASG provides the secretariat to the All Party Parliamentary Group for Allergy.
Year(s) Of Engagement Activity 2024,2025
URL https://www.nasguk.org/about-us/
 
Description Podcast for BBC World Service CrowdScience show 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Invited to record podcast by BBC CrowdScience to address if "allergies" are increasing in the world, and how this varies from one country to another. Also to explain different sort of allergy tests, and their pitfalls.
Year(s) Of Engagement Activity 2025
 
Description Presentation to National Medical Students conference in paediatrics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact Invited to speak at National Medical Students meeting to explain about paediatric allergy and routes to become involved in this area, as a medical student and/or junior doctor.
Year(s) Of Engagement Activity 2025
URL https://www.bacch.org.uk/events/imperial-college-icsm-national-paediatrics-conference-2025-london
 
Description Programme to develop new Service Standards for Paediatric Allergy Services in the NHS 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I am leading a programme of work to define new Service Standards for Paediatric Allergy Services in the NHS on behalf of BSACI and RCPCH. This has included extensive PI through stakeholder engagement, prioritisation workshops.
Year(s) Of Engagement Activity 2023,2024
 
Description United Nations FAO / WHO Expert Panel on Food Allergens 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Member of the FAO/WHO Expert Panel on risk management of food allergens, to inform Codex Alimentarus discussions
Year(s) Of Engagement Activity 2019,2020,2021,2022,2023
URL https://www.who.int/publications/m/item/ad-hoc-joint-fao-who-expert-consultation-on-risk-assessment-...
 
Description Working group on Precautionary Allergy Labelling for healthcare professionals 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Working group building on FAO/WHO Codex discussions to build global consensus amongst HCPs working in allergy globally in terms of support (or not) for Codex recommendations.
Year(s) Of Engagement Activity 2024,2025