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.
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.
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

Anagnostou A
(2023)
The future of food allergy: Challenging existing paradigms of clinical practice.
in Allergy

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

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

Cardona V
(2023)
[Erratum : World Allergy Organization Anaphylaxis Guidance 2020 [Japanese Journal of Allergology Vol.70 (2021) No.9 p.1211-1234]].
in Arerugi = [Allergy]

Deschildre A
(2024)
Towards a common approach for managing food allergy and serious allergic reactions (anaphylaxis) at school. GA 2 LEN and EFA consensus statement
in Clinical and Translational Allergy

Dodd A
(2024)
Emergency treatment of peri-operative anaphylaxis: Resuscitation Council UK algorithm for anaesthetists.
in Anaesthesia

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

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

Gold MS
(2023)
Anaphylaxis: Revision of the Brighton collaboration case definition.
in Vaccine

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 |