Mechanisms underlying the physiological and cellular response to food allergen challenge in human subjects with peanut allergy
Lead Research Organisation:
Imperial College London
Department Name: Dept of Medicine
Abstract
Food allergy affects up to 2% of adults and 8% of children in the UK, and can cause life-threatening reactions (anaphylaxis) in some but not all individuals. The mainstay of management remains dietary avoidance. There is no effective treatment for preventing allergic reactions, which can be fatal even when rescue medication is given in a timely manner.
Allergic reactions to food are mediated through the Immunoglobulin E (IgE) antibody. The binding of allergenic proteins in food to IgE causes the release of different chemical mediators, including histamine. Much of our knowledge of the mechanism is derived from animal models, but this may not be representative of the situation in man. Antihistamines can prevent fatality in animal models of anaphylaxis but are much less effective in man, possibly because humans are 1000-fold more sensitive to the effects of histamine than, for example, mice. Furthermore, anaphylaxis in peanut-allergic humans can be triggered by tiny amounts of protein (under 10mg or 1/30 of a single peanut). By comparison, very high levels are required to cause anaphylaxis by the oral route in mouse models, equivalent to a person eating over 1000 peanuts. These examples demonstrate the difficulties of extrapolating data from animal models to man.
The diagnosis of food allergy can be confirmed by the detection of specific IgE to the trigger food, either by blood or skin testing. Unfortunately, while levels of specific IgE predict the likelihood of reaction after exposure, they do not predict the severity of reaction. While some risk factors have been identified for anaphylaxis (e.g. asthma, underlying heart disease, previous anaphylaxis), the majority of patients do not have a risk factor. Health professionals are therefore unable to determine who is at risk of anaphylaxis, resulting in widespread prescribing of adrenaline auto-injector pens for emergency rescue treatment. The prescription of these devices has increased over the past decade, from 74,600 devices in England in 2000 to over 230,000 devices in 2010, at a cost of £12.5m. The vast majority of these devices are never used, and their prescription is a significant cost to the health service. Any data facilitating improved risk stratification of allergic individuals would assist health professionals in providing reassurance to patients and parents alike, as well as delivering economic savings.
Given the importance of dietary avoidance in the management of food allergies, the Food Standards Agency (FSA) is commissioning a study to determine the amount of peanut which needs to be consumed to trigger a reaction. This threshold varies significantly between individuals, but also within the same person, depending on a number of poorly understood factors including exercise. The aim is to define a safe level of potential food contamination below which peanut-allergic individuals will not react, thus informing the food industry and better protecting the allergic population. The study will recruit 100 peanut-allergic volunteers, each undergoing controlled exposure to peanut or placebo under medical supervision on different occasions.
The FSA study provides a unique opportunity to assess the mechanism of food allergic reactions, and determine the extent to which data from animal models are applicable to man. We propose to monitor the effects of food allergic reactions on:
- the absorption of food proteins in the mouth, to see if this changes as the reaction progresses
- the release of different chemical mediators in blood, saliva and urine.
- changes in blood flow, both at the site of reaction and beyond, using non-invasive techniques
Our data will provide valuable insight into the mechanisms underlying food allergic reactions in man, highlighting new targets for future diagnostic tests and therapies. We further plan to develop new strategies to improve risk stratification, in order to improve management of peanut allergic individuals.
Allergic reactions to food are mediated through the Immunoglobulin E (IgE) antibody. The binding of allergenic proteins in food to IgE causes the release of different chemical mediators, including histamine. Much of our knowledge of the mechanism is derived from animal models, but this may not be representative of the situation in man. Antihistamines can prevent fatality in animal models of anaphylaxis but are much less effective in man, possibly because humans are 1000-fold more sensitive to the effects of histamine than, for example, mice. Furthermore, anaphylaxis in peanut-allergic humans can be triggered by tiny amounts of protein (under 10mg or 1/30 of a single peanut). By comparison, very high levels are required to cause anaphylaxis by the oral route in mouse models, equivalent to a person eating over 1000 peanuts. These examples demonstrate the difficulties of extrapolating data from animal models to man.
The diagnosis of food allergy can be confirmed by the detection of specific IgE to the trigger food, either by blood or skin testing. Unfortunately, while levels of specific IgE predict the likelihood of reaction after exposure, they do not predict the severity of reaction. While some risk factors have been identified for anaphylaxis (e.g. asthma, underlying heart disease, previous anaphylaxis), the majority of patients do not have a risk factor. Health professionals are therefore unable to determine who is at risk of anaphylaxis, resulting in widespread prescribing of adrenaline auto-injector pens for emergency rescue treatment. The prescription of these devices has increased over the past decade, from 74,600 devices in England in 2000 to over 230,000 devices in 2010, at a cost of £12.5m. The vast majority of these devices are never used, and their prescription is a significant cost to the health service. Any data facilitating improved risk stratification of allergic individuals would assist health professionals in providing reassurance to patients and parents alike, as well as delivering economic savings.
Given the importance of dietary avoidance in the management of food allergies, the Food Standards Agency (FSA) is commissioning a study to determine the amount of peanut which needs to be consumed to trigger a reaction. This threshold varies significantly between individuals, but also within the same person, depending on a number of poorly understood factors including exercise. The aim is to define a safe level of potential food contamination below which peanut-allergic individuals will not react, thus informing the food industry and better protecting the allergic population. The study will recruit 100 peanut-allergic volunteers, each undergoing controlled exposure to peanut or placebo under medical supervision on different occasions.
The FSA study provides a unique opportunity to assess the mechanism of food allergic reactions, and determine the extent to which data from animal models are applicable to man. We propose to monitor the effects of food allergic reactions on:
- the absorption of food proteins in the mouth, to see if this changes as the reaction progresses
- the release of different chemical mediators in blood, saliva and urine.
- changes in blood flow, both at the site of reaction and beyond, using non-invasive techniques
Our data will provide valuable insight into the mechanisms underlying food allergic reactions in man, highlighting new targets for future diagnostic tests and therapies. We further plan to develop new strategies to improve risk stratification, in order to improve management of peanut allergic individuals.
Technical Summary
AIMS
1) To investigate the pathophysiology of acute allergic reactions to peanut, and how this relates to severity of clinical symptoms, by assessing mucosal absorption of allergen, cellular activation and vascular physiology.
2) To understand the process by which exercise may alter the character of food allergic reactions.
METHODS
This fellowship will capitalize on a recently funded trial involving repeated double-blind placebo-controlled food challenge (DBPCFC) of peanut-allergic adults under controlled conditions. We will assess mechanisms of the acute reaction to a food allergen through:
- assays for biomarkers (blood, saliva, urine) including kinins, complement, leukotrienes and mast cell proteases. Leukocyte activation will be determined by poylchromatic flow cytometry
- Assessment of local and systemic changes in vascular flow and permeability, using established non-invasive techniques
- the above techniques will be repeated with DBPCFC after exercise
SCIENTIFIC AND MEDICAL OPPORTUNITIES
1) Investigate how the pathophysiology of acute allergic reactions to food differs from that of non-food triggers, which are not often associated with systemic effects. This will highlight new targets for future therapeutic interventions, as well as facilitate risk stratification of peanut allergic individuals
2) Determine the extent to which animal models of food allergy are applicable to man.
3) Allow for characterisation of peanut allergic individuals in terms of peanut-specific antibody production (IgE, IgG, IgG4, IgA, free Ig light chain) and how this relates to reaction severity
4) Validation of novel salivary markers of allergic reactions, improving diagnostic opportunities in patients in whom diagnosis is unclear
5) Synergistic collaborations with the pan-European project on Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM), which will investigate intrinsic and extrinsic factors affecting the severity of reactions to foods.
1) To investigate the pathophysiology of acute allergic reactions to peanut, and how this relates to severity of clinical symptoms, by assessing mucosal absorption of allergen, cellular activation and vascular physiology.
2) To understand the process by which exercise may alter the character of food allergic reactions.
METHODS
This fellowship will capitalize on a recently funded trial involving repeated double-blind placebo-controlled food challenge (DBPCFC) of peanut-allergic adults under controlled conditions. We will assess mechanisms of the acute reaction to a food allergen through:
- assays for biomarkers (blood, saliva, urine) including kinins, complement, leukotrienes and mast cell proteases. Leukocyte activation will be determined by poylchromatic flow cytometry
- Assessment of local and systemic changes in vascular flow and permeability, using established non-invasive techniques
- the above techniques will be repeated with DBPCFC after exercise
SCIENTIFIC AND MEDICAL OPPORTUNITIES
1) Investigate how the pathophysiology of acute allergic reactions to food differs from that of non-food triggers, which are not often associated with systemic effects. This will highlight new targets for future therapeutic interventions, as well as facilitate risk stratification of peanut allergic individuals
2) Determine the extent to which animal models of food allergy are applicable to man.
3) Allow for characterisation of peanut allergic individuals in terms of peanut-specific antibody production (IgE, IgG, IgG4, IgA, free Ig light chain) and how this relates to reaction severity
4) Validation of novel salivary markers of allergic reactions, improving diagnostic opportunities in patients in whom diagnosis is unclear
5) Synergistic collaborations with the pan-European project on Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM), which will investigate intrinsic and extrinsic factors affecting the severity of reactions to foods.
Planned Impact
1. Health and Social Outputs : Individuals
Study participants: will benefit directly from an awareness of their symptoms and the amount of food allergen needed to trigger this. Previous studies have demonstrated that patients undergoing diagnostic food challenges report an improvement in quality of life measures within a short timeframe (months), even where the challenge is 'positive'.
Patients and their families: Up to 8% of children and 2% of adults in the UK have food allergies; this has a high impact on a patient's quality of life, along with their carers (e.g. parents of affected children). This study will complement the results from the threshold-determining study, by providing additional data relating to the allergic reaction, and whether levels of exposure around the threshold cause reproducible reactions in terms of symptom severity. This will inform policy relating to allergen labelling of foods in terms of potential cross-contamination, resulting in benefits to the wider food-allergic population in the UK. It is hoped that this will take place within 3-5 years. Longer-term, the study will highlight future therapeutic targets which may be useful in the future management of severe reactions.
Health professionals: will be better able to offer reassurance to those affected by food allergies, on the basis of a greater understanding of mechanisms involved and improved tools to determine who is at risk of severe symptoms. The validation of diagnostic techniques for food allergic reactions (e.g. salivary testing) will be of particular utility for professionals in the emergency services and A&E departments. These benefits should commence within the period of this grant, once results have been published in peer-reviewed journals.
2. Health and Social Outputs : Public Services and Health Policy
UK & Europe Policy makers: The results will be used to inform data relating to Minimal Eliciting Doses for the food-allergic population and the required safety factor, in order to inform industry and with a view to protecting the allergic population. This has been determined to be a priority by the Food Standards Agency (FSA). Through my proposed collaboration in the EU-funded project on Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM), there will also be significant benefits to EU policy makers.
Health policy: Improved risk stratification of peanut-allergic individuals will allow a more targeted provision of education and rescue medications (such as adrenaline autoinjector devices), with associated cost benefits.
Voluntary sector: A number of support groups and charities have been established to support food-allergic patients and their families. Food allergy has a high impact on quality of life measures. By providing information relating to risk assessment and allergen avoidance, the study will empower these groups to provide more comprehensive information to allergic individuals in the UK, within a timeframe similar to that of the publication of the study results (as described above).
3. Economic benefits : National and Global
Food allergy is increasing throughout the world, and is now a global issue, particularly with the export of foods from one country to another. Some countries (e.g. Australia) have already attempted to rationalise allergen labelling of foods in order to provide clearer information to consumers, though the success of this initiative is debatable. Europe, and in particular the FSA, are taking a more quantitative, evidence-based approach. In conjunction with good manufacturing practice, this initiative can be expected to provide a competitive advantage in the provision of foods with appropriate labelling for allergy sufferers. European researchers are leading the world in advancing this important area of investigation.
Study participants: will benefit directly from an awareness of their symptoms and the amount of food allergen needed to trigger this. Previous studies have demonstrated that patients undergoing diagnostic food challenges report an improvement in quality of life measures within a short timeframe (months), even where the challenge is 'positive'.
Patients and their families: Up to 8% of children and 2% of adults in the UK have food allergies; this has a high impact on a patient's quality of life, along with their carers (e.g. parents of affected children). This study will complement the results from the threshold-determining study, by providing additional data relating to the allergic reaction, and whether levels of exposure around the threshold cause reproducible reactions in terms of symptom severity. This will inform policy relating to allergen labelling of foods in terms of potential cross-contamination, resulting in benefits to the wider food-allergic population in the UK. It is hoped that this will take place within 3-5 years. Longer-term, the study will highlight future therapeutic targets which may be useful in the future management of severe reactions.
Health professionals: will be better able to offer reassurance to those affected by food allergies, on the basis of a greater understanding of mechanisms involved and improved tools to determine who is at risk of severe symptoms. The validation of diagnostic techniques for food allergic reactions (e.g. salivary testing) will be of particular utility for professionals in the emergency services and A&E departments. These benefits should commence within the period of this grant, once results have been published in peer-reviewed journals.
2. Health and Social Outputs : Public Services and Health Policy
UK & Europe Policy makers: The results will be used to inform data relating to Minimal Eliciting Doses for the food-allergic population and the required safety factor, in order to inform industry and with a view to protecting the allergic population. This has been determined to be a priority by the Food Standards Agency (FSA). Through my proposed collaboration in the EU-funded project on Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM), there will also be significant benefits to EU policy makers.
Health policy: Improved risk stratification of peanut-allergic individuals will allow a more targeted provision of education and rescue medications (such as adrenaline autoinjector devices), with associated cost benefits.
Voluntary sector: A number of support groups and charities have been established to support food-allergic patients and their families. Food allergy has a high impact on quality of life measures. By providing information relating to risk assessment and allergen avoidance, the study will empower these groups to provide more comprehensive information to allergic individuals in the UK, within a timeframe similar to that of the publication of the study results (as described above).
3. Economic benefits : National and Global
Food allergy is increasing throughout the world, and is now a global issue, particularly with the export of foods from one country to another. Some countries (e.g. Australia) have already attempted to rationalise allergen labelling of foods in order to provide clearer information to consumers, though the success of this initiative is debatable. Europe, and in particular the FSA, are taking a more quantitative, evidence-based approach. In conjunction with good manufacturing practice, this initiative can be expected to provide a competitive advantage in the provision of foods with appropriate labelling for allergy sufferers. European researchers are leading the world in advancing this important area of investigation.
Organisations
- Imperial College London (Fellow, Lead Research Organisation)
- University of Manchester (Collaboration)
- PUBLIC HEALTH ENGLAND (Collaboration)
- MANCHESTER UNIVERSITY NHS FOUNDATION TRUST (Collaboration)
- Allergenis (Collaboration)
- ICNARC Case Mix Programme (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- French National Institute of Agricultural Research (Collaboration)
- University Clinic Golnik (Collaboration)
- University College Cork (Collaboration)
- UNSW Sydney (Collaboration)
- Netherlands Organization for Applied Scientific Research (TNO) (Collaboration)
- Children's Hospital of Philadelphia (Collaboration)
- UNIVERSITY OF SYDNEY (Collaboration)
People |
ORCID iD |
Paul Turner (Principal Investigator / Fellow) |
Publications
Allen KJ
(2014)
Precautionary labelling of foods for allergen content: are we ready for a global framework?
in The World Allergy Organization journal
Alviani C
(2020)
Anaphylaxis Refractory to intramuscular adrenaline during in-hospital food challenges: A case series and proposed management.
in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Anagnostou A
(2022)
Fatal Food Anaphylaxis: Distinguishing Fact From Fiction.
in The journal of allergy and clinical immunology. In practice
Anagnostou K
(2019)
Myths, facts and controversies in the diagnosis and management of anaphylaxis.
in Archives of disease in childhood
Arasi S
(2021)
Consensus on DEfinition of Food Allergy SEverity (DEFASE) an integrated mixed methods systematic review.
in The World Allergy Organization journal
Bahri R
(2018)
Mast cell activation test in the diagnosis of allergic disease and anaphylaxis
in Journal of Allergy and Clinical Immunology
Baseggio Conrado A
(2021)
Global patterns in anaphylaxis due to specific foods: A systematic review.
in The Journal of allergy and clinical immunology
Baseggio Conrado A
(2021)
Food anaphylaxis in the United Kingdom: analysis of national data, 1998-2018.
in BMJ (Clinical research ed.)
Bernard H
(2020)
Circulating Ara h 6 as a marker of peanut protein absorption in tolerant and allergic humans following ingestion of peanut-containing foods.
in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Blom W
(2022)
Updated full range of Eliciting Dose values for Cow's milk for use in food allergen risk assessment
in Food and Chemical Toxicology
Description | AAAAI Taskforce on adrenaline autoinjector devices |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | Allergen management on aircraft |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to a national consultation/review |
Description | Brighton Collaboration : Anaphylaxis case definition |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | COT |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | Invited to be expert member to the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), an independent scientific committee that provides advice to the Food Standards Agency, the Department of Health and other Government Departments and Agencies on matters concerning the toxicity of chemicals. Remit relates to a review by COT of strategies which might affect atopic outcomes in pregnancy/children/adulthood. |
Description | COVID-vaccine allergy |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Working with MHRA, PHE and NHS-E in implementation of COVID vaccine programme, I built a surveillance system for reporting AEs to the vaccines which has been implemented by MHRA, PHE and NHS-E to collect data relating to possible allergic reactions in order to provide confidence over the risks and measures to mitigate against them. Also contributed to Green Book chapter on COVID vaccines, through my hon role at PHE. |
URL | https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/9612... |
Description | European Allergen Immunotherapy taskforce |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
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 | FSA/DEFRA labelling |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to a national consultation/review |
Impact | Asked to provide ongoing expert input into a government (FSA/DEFRA) consultatation on improving allergen labelling relating to PPDS food products. |
Description | Generic AAI |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | Member of steering group which has worked and lobbied DoH and MHRA for a change in UK legislation to allow generic adrenaline autoinjectors in schools and other educational settings. This MHRA have agreed to a change in legislation and we are working with a variety of stakeholder groups including DH and D.Ed. to provide national guidance to schools in the management of allergic reactions and the use of the generic adrenaline. |
URL | http://www.anaphylaxis.org.uk/campaigning/generic-pen-campaign/ |
Description | Green Book guidance - asthma and influenza vaccination |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Advised the Joint Committee on Vaccination and Immunisation (JCVI) which advises UK health departments on immunisation relating to influenza in chidlren with asthma, and redrafted official government guidance on vaccination |
URL | https://www.gov.uk/government/publications/influenza-the-green-book-chapter-19 |
Description | JCVI / Dept of Health |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Asked to advise the Joint Committee on Vaccination and Immunisation (JCVI) which advises UK health departments on immunisation relating to influenza. |
URL | https://www.gov.uk/government/publications/influenza-the-green-book-chapter-19 |
Description | NICE Diagnostic Assessment |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Membership of a guideline committee |
Description | RCUK Anaphylaxis Guideline |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Impact | Co-lead of update to Resuscitation Council UK Guideline 2021. As part of this, we worked with PHE and RCGP to release urgent advice to Vaccination Centres for COVID-19 to ensure appropriate training of staff delivering vaccines in community hubs |
URL | https://www.resus.org.uk/about-us/news-and-events/rcuk-publishes-anaphylaxis-guidance-vaccination-se... |
Description | SACN/COT committee on infant feeding |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to a national consultation/review |
Impact | Invited to be member of DoH expert committee (SACN/COT) on drafting Government guidelines on infant feeding |
URL | https://cot.food.gov.uk/committee/committee-on-toxicity/cotwg/joint-sacn/cot-working-group-on-the-ti... |
Description | UCT Paediatric Allergy/PICU meeting |
Geographic Reach | Africa |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Guest speaker/trainer at National Paediatric Training meeting in S. Africa, which attracted HCPs from across Africa as well as from South Africa. I gave 3 sessions on diagnosis/management of anaphylaxis, with a number of approaches afterwards to discuss improvements in the clinical management of anaphylaxis. |
Description | United Nations FAO/World Health Organisation Expert Consultation on Food Allergens |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | Published reports have already had impact on national regulators, with many such organisations considering status quo and how this might change in the future to better protect the food-allergic public. |
URL | https://www.who.int/news-room/events/detail/2021/03/15/default-calendar/ad-hoc-joint-fao-who-expert-... |
Description | WAO Anaphylaxis Committee |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Description | BRC Funding |
Amount | £153,000 (GBP) |
Organisation | National Institute for Health Research |
Department | NIHR Imperial Biomedical Research Centre |
Sector | Public |
Country | United Kingdom |
Start | 06/2014 |
End | 03/2016 |
Description | Department of Health Policy Research Programme |
Amount | £2,061,500 (GBP) |
Funding ID | PR-R17-0916-22001 |
Organisation | Government of Wales |
Department | Department of Health |
Sector | Public |
Country | United Kingdom |
Start | 08/2017 |
End | 08/2020 |
Description | Exploring mechanisms to optimise the duration of oral immunotherapy for peanut allergy |
Amount | £1,071,974 (GBP) |
Funding ID | MR/W025639/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2025 |
Description | FP7 iFAAM collaboration |
Amount | € 130,000 (EUR) |
Funding ID | 312147 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 08/2015 |
End | 02/2017 |
Description | Identifying risks for severe life-threatening allergic reactions to foods (IRIS-Allergy) |
Amount | £1,020,009 (GBP) |
Funding ID | MR/W018616/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2022 |
End | 05/2025 |
Description | MRC Confidence in Concepts Award |
Amount | £55,400 (GBP) |
Funding ID | ICL P50832 |
Organisation | Medical Research Council (MRC) |
Department | MRC Confidence in Concept Scheme |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2014 |
End | 04/2015 |
Description | MRC Confidence in Concepts Award |
Amount | £55,426 (GBP) |
Funding ID | ICL PS2531_WMNP and PS2563_WMNP |
Organisation | Medical Research Council (MRC) |
Department | MRC Confidence in Concept Scheme |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2015 |
End | 03/2016 |
Description | MRC DPFS |
Amount | £1,031,452 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2019 |
End | 06/2022 |
Description | NIHR EME |
Amount | £1,742,727 (GBP) |
Organisation | NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2020 |
End | 12/2023 |
Description | National Vaccine Evaluation Consortium, Department of Health |
Amount | £245,000 (GBP) |
Funding ID | 039/0031 |
Organisation | Public Health England |
Sector | Public |
Country | United Kingdom |
Start | 08/2013 |
End | 02/2015 |
Description | National Vaccine Evaluation Consortium, Department of Health |
Amount | £60,000 (GBP) |
Funding ID | 039/0031 |
Organisation | Public Health England |
Sector | Public |
Country | United Kingdom |
Start | 08/2015 |
End | 07/2016 |
Description | Optimising immunotherapy for peanut allergy in the UK to improve patient safety |
Amount | £22,319 (GBP) |
Funding ID | 2834 |
Organisation | Action Medical Research |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2021 |
End | 10/2024 |
Description | Research Grant |
Amount | $180,050 (USD) |
Organisation | End Allergies Together |
Sector | Charity/Non Profit |
Country | United States |
Start | 04/2016 |
End | 12/2017 |
Description | SOCMA Study |
Amount | £295,407 (GBP) |
Organisation | J P Moulton Charitable Foundation |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2020 |
Description | Using NHS data to monitor trends in the occurrence of severe, food induced allergic reactions |
Amount | £443,010 (GBP) |
Funding ID | FS101222 |
Organisation | Food Standards Agency (FSA) |
Sector | Public |
Country | United Kingdom |
Start | 12/2019 |
End | 01/2022 |
Title | Mast cell activation test |
Description | Together with our collaboration partners in Manchester, we have successfully developed the mast cell activation test as a tool in allergy diagnostics, and in the assessment of the relative contributions of mast cells to IgE-mediated pathologies. |
Type Of Material | Model of mechanisms or symptoms - in vitro |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Further grant submissions |
Title | Anaphylaxis registry |
Description | UK National Register of Fatal Anaphylaxis |
Type Of Material | Database/Collection of data |
Provided To Others? | No |
Impact | Publications highlighting risk factors for severe food allergic reactions. Pilot data for case-control study to identify risk factors of severity in food allergy. |
Description | Anaphylaxis Registry |
Organisation | Manchester University NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | Review and cleaning of existing UK fatal anaphylaxis data, collection of prospective data |
Collaborator Contribution | Review and cleaning of existing UK fatal anaphylaxis data, collection of prospective data |
Impact | Publication pending |
Start Year | 2013 |
Description | CHOP |
Organisation | Children's Hospital of Philadelphia |
Department | Division of Allergy |
Country | United States |
Sector | Hospitals |
PI Contribution | Successful award of a grant from the EAT foundation (USA) to look at transcriptomics during peanut-induced allergic reactions: provision of blood samples, clinical data and analysis |
Collaborator Contribution | Successful award of a grant from the EAT foundation (USA) to look at transcriptomics during peanut-induced allergic reactions: analysis of blood samples. |
Impact | nil to date - collaboration only just commenced |
Start Year | 2016 |
Description | Epitope mapping |
Organisation | Allergenis |
Country | United States |
Sector | Private |
PI Contribution | Supplied clinical data and patient samples for analysis |
Collaborator Contribution | Epitope analysis to include in our data science approach to predict phenotypes relating to peanut allergy |
Impact | Submitted abstract to EAACI 2019 |
Start Year | 2018 |
Description | ICNARC |
Organisation | ICNARC Case Mix Programme |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Joint funding application to analysis ICU admissions due to anaphylaxis in England and Wales |
Collaborator Contribution | Joint funding application to analysis ICU admissions due to anaphylaxis in England and Wales |
Impact | Funding application (submitted) |
Start Year | 2015 |
Description | INRA |
Organisation | French National Institute of Agricultural Research |
Country | France |
Sector | Academic/University |
PI Contribution | Supply of biologicial samples for laboratory analysis |
Collaborator Contribution | Laboratory analysis of food proteins in biological samples |
Impact | Pilot data |
Start Year | 2014 |
Description | Influenza collaboration |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Designing and executing a clinical trial assessing efficacy and immunological response to nasal influenza vaccination in children. |
Collaborator Contribution | Funding pilot work for an MRC application to assess immunological responses to nasal influenza vaccination, resulting in biological samples to be available for assay |
Impact | MRC Grant application (through to final round) |
Start Year | 2017 |
Description | Influenza collaboration |
Organisation | Public Health England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Designing and executing a clinical trial assessing efficacy and immunological response to nasal influenza vaccination in children. |
Collaborator Contribution | Funding pilot work for an MRC application to assess immunological responses to nasal influenza vaccination, resulting in biological samples to be available for assay |
Impact | MRC Grant application (through to final round) |
Start Year | 2017 |
Description | Mast Cell Activation Test |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Contribution of clinical samples / clinical data / expertise towards development of new diagnostic test for food allergy |
Collaborator Contribution | Provision of lab data towards improving understanding of food allergy mechanisms and comparative assessment of the performance characteristics of different diagnostic tests |
Impact | Various conference presentations and publications. MRC DFPS Award (2019-) |
Start Year | 2016 |
Description | PHE |
Organisation | Public Health England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Head of collaboration for multicentre CTIMP assessing safety of egg-containing vaccine in egg-allergic children including those with history of severe allergic reactions |
Collaborator Contribution | Funding and statistical support |
Impact | Report to MHRA x 2. 4 conference abstracts. Change in UK vaccination policy achieved. Further study funded. 3 x papers published. |
Start Year | 2013 |
Description | Pero Korosec, Slovenia |
Organisation | University Clinic Golnik |
Country | Slovenia |
Sector | Academic/University |
PI Contribution | Provision of samples and data from food challenges to peanut, to determine pathophysiological changes during allergic reactions |
Collaborator Contribution | Provision of samples and data from patients undergoing acute allergic reactions to venom, presenting to the emergency department, to determine pathophysiological changes during allergic reactions |
Impact | 1 Accepted manuscript to J. Allergy Clin Immunol., to date. |
Start Year | 2016 |
Description | TNO |
Organisation | Netherlands Organization for Applied Scientific Research (TNO) |
Country | Netherlands |
Sector | Public |
PI Contribution | Contributed with data and methodology towards risk assessment methodology for food industry with respect to food allergens. Negotiations are underway to fund a 2 year MD project at Imperial College London. |
Collaborator Contribution | TNO have provided analysis for data relating to food allergen thresholds and the effect of food processing on these. |
Impact | Conference abstract. Paper in submission. |
Start Year | 2015 |
Description | TRACE |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Mechanistic investigations to food allergic reactions |
Collaborator Contribution | Resources in order to fund and excecute DBPCFC food challenges in allergic adults |
Impact | nil to date |
Start Year | 2013 |
Description | TRACE |
Organisation | University of Manchester |
Department | Institute of Inflammation and Repair |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Mechanistic investigations to food allergic reactions |
Collaborator Contribution | Resources in order to fund and excecute DBPCFC food challenges in allergic adults |
Impact | nil to date |
Start Year | 2013 |
Description | UCC |
Organisation | University College Cork |
Country | Ireland |
Sector | Academic/University |
PI Contribution | Data relating to reaction thresholds, interpretation of food allergen labels, research methodology, survey. |
Collaborator Contribution | Data relating to reaction thresholds, interpretation of food allergen labels, research methodology, data analysis |
Impact | Plans for a pan-European survey to assess consumer approaches to allergen labelling interpretation |
Start Year | 2015 |
Description | UNSW |
Organisation | University of New South Wales |
Department | Faculty of Engineering |
Country | Australia |
Sector | Academic/University |
PI Contribution | Provision of samples and clinical data relating to peanut-allergic individuals, to assess IgE-immunoblot changes during desensitisation in peanut allergy |
Collaborator Contribution | IgE-immunoblot changes during desensitisation in peanut allergy |
Impact | Nil to date - collaboration only just commenced |
Start Year | 2016 |
Description | USyd |
Organisation | University of Sydney |
Country | Australia |
Sector | Academic/University |
PI Contribution | Joint clinical study: pilot study being performed in London, UK with analysis of samples and future 2 centre study involving UK and Australia |
Collaborator Contribution | Intellectual input, provision of IMP equivalent, lab analysis |
Impact | pending |
Start Year | 2013 |
Description | iFAAM |
Organisation | University of Manchester |
Department | Institute of Inflammation and Repair |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | 1) Development of a severity score system for food-induced allergic reactions 2) Strategic approaches to 'may contain' precautionary statements on food labels |
Collaborator Contribution | Synergies with regards to severity score |
Impact | 2 review articles (one published to date, one under review) |
Start Year | 2013 |
Title | BOPI |
Description | Phase 2/3 RCT to evaluate use of modified peanut allergen in oral immunotherapy for peanut allergy |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Late clinical evaluation |
Year Development Stage Completed | 2016 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
UKCRN/ISCTN Identifier | ACTRN12614000265673 |
Impact | The pilot data has led to a AUD$1.6million award from NHMRC for a follow-on study, on which I am a co-I. |
URL | https://clinicaltrials.gov/ct2/show/NCT02149719 |
Title | BOPI-2 study |
Description | Ongoing clinical trial (non-CTIMP) to evaluate whether boiled peanut oral immunotherapy is at least as effective as peanut flour in treating children with peanut allergy. The study will compare the rate of adverse events and other safety outcomes between these two interventions, and assess the immunological mechanisms involved, a secondary aim being to develop clinically-useful predictors for identifying individuals likely to undergo successful desensitisation. |
Type | Therapeutic Intervention - Drug |
Year Development Stage Completed | 2018 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | Study follows-on from the original BOPI study, to evaluate the feasibility of introducing boiled peanut OIT into NHS practice. |
Title | Fluenz (LAIV) |
Description | Efficacy and safety of Fluenz (intranasal influenza vaccine) in atopic children |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Market authorisation |
Year Development Stage Completed | 2015 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | Data has supported change in national vaccine policy |
URL | https://clinicaltrials.gov/ct2/show/NCT02549365 |
Title | Fluenz (LAIV) |
Description | Safety of Fluenz (intranasal influenza vaccine in children with egg allergy +/- asthma |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Late clinical evaluation |
Year Development Stage Completed | 2014 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | change in UK public vaccination policy |
URL | http://clinicaltrials.gov/show/NCT02111512 |
Title | Fluenz Tetra (LAIV) |
Description | SNIFFLE-4 Study is a nationwide, multicentre study assessing the safety of Fluenz Tetra in children with moderate-severe asthma. The vaccine is currently available in UK and is part of the national childhood immunisation schedule. However, it's use in asthma is a relative contra-indication. I am the national CI on the study. |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Wide-scale adoption |
Year Development Stage Completed | 2017 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | The study results will feed directly in PHE guidance for influenza vaccination. |
URL | https://clinicaltrials.gov/show/NCT02866942 |
Title | SNIFFLE Study |
Description | Assessing safety of Fluenz LAIV immunisation in egg-allergic children; DoH funded. |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Market authorisation |
Year Development Stage Completed | 2013 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | Demonstration of safety of Fluenz vaccination in egg-allergic children, facilitating nationwide roll-out of universal flu vaccination in children improving streamlined delivery of vaccination programme. |
URL | http://clinicaltrials.gov/show/NCT01859039 |
Title | SOCMA study |
Description | Phase 2b/3 clinical trial evaluating combination approach to milk allergy desensitisation |
Type | Therapeutic Intervention - Complementary |
Current Stage Of Development | Refinement. Clinical |
Year Development Stage Completed | 2018 |
Development Status | Actively seeking support |
Clinical Trial? | Yes |
Impact | Study due to report early 2020 |
URL | https://clinicaltrials.gov/show/NCT02216175 |
Description | Airline company |
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 | Advisory panel to a major international airline on medical procedures in-flight with respect to anaphylaxis emergencies |
Year(s) Of Engagement Activity | 2019 |
Description | Akademie Fresenius |
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 | 2 day workshop / expert panel on improving allergen risk management in food industry |
Year(s) Of Engagement Activity | 2015 |
URL | https://www.akademie-fresenius.com/company/press/news-details/eliminationsdiaet-bei-lebensmittelalle... |
Description | Anaphylaxis Campaign support group |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | 15 parents of food allergic children Follow up from 2 parents seeking further information |
Year(s) Of Engagement Activity | 2013,2014,2015 |
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 4 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Filming for a BBC documentary on blood and allergy Film yet to be aired |
Year(s) Of Engagement Activity | 2014 |
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 | EAACI Severity meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Invovled in European working group on anaphylaxis diagnosis and management pending |
Year(s) Of Engagement Activity | 2014 |
Description | FSA Adult allergy |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Scoping group to define research strategy for Food Standards Agency |
Year(s) Of Engagement Activity | 2016 |
Description | FSA Review on Food Hypersensitivities |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | Various engagement workshops in my capacity as lead for an independent review into Food Allergy & Hypersensitivity Research commissioned by FSA in last 10 years |
Year(s) Of Engagement Activity | 2018,2019,2020 |
Description | Food Allergy Research Programme - BBC interviews |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Interview/filming with BBC |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.bbc.co.uk/news/uk-wales-48473190 |
Description | Food Matters |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Food Matters Live meeting at Excel - presentation on allergy labelling to general public with Q&A afterwards |
Year(s) Of Engagement Activity | 2015 |
Description | Generic adrenaline autoinjectors / MHRA |
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 | Working group to work with DoH/MHRA to facilitate change in UK legislation allowing generic adrenaline autoinjectors into schools |
Year(s) Of Engagement Activity | 2015,2016,2017 |
Description | Generic adrenaline pens in schools |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Led project/working group including patient representatives to develop DoH-funded resources including website to support changes in legislation allowing "spare" adrenaline auto-injectors in schools. |
Year(s) Of Engagement Activity | 2017,2018 |
URL | http://www.sparepensinschools.uk |
Description | ILSI Severity |
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 | Ongoing ILSI expert group on assessing relationship between exposure dose and severity of resulting allergic reactions, to inform allergen risk management |
Year(s) Of Engagement Activity | 2015,2016 |
URL | http://www.ilsi.org/Europe/Pages/Food-Allergy-Expert-Groups.aspx |
Description | ITV regional news |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Filmed for brief slot on allergy awareness week for ITV regional news none specific |
Year(s) Of Engagement Activity | 2014 |
URL | https://www.youtube.com/watch?v=d86SRfBk1s4 |
Description | Infant Feeding Advice - working group |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Led a working group of healthcare professionals (doctors, nurses, dietitians, health visitors) to write national guidance on the introduction of allergenic foods into the infant diet, with input from parents/public/patient rep groups |
Year(s) Of Engagement Activity | 2017,2018 |
Description | NRP Radio interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Radio interview with NRP Washington to discuss management of anaphylaxis, and in particular, use of adrenaline autoinjectors |
Year(s) Of Engagement Activity | 2016 |
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 | Sunday Times article |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Interviewed for Sunday Times magazine central feature on food allergy |
Year(s) Of Engagement Activity | 2019 |
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 | Updated info sheets: Anaphylaxis Campaign |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Edited information sheet (online) for Anaphylaxis Campaign |
Year(s) Of Engagement Activity | 2016 |
Description | Working group: FPIES |
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 | International guidelines on the management of FPIES |
Year(s) Of Engagement Activity | 2015,2016,2017 |
URL | http://www.jacionline.org/article/S0091-6749(17)30153-7/fulltext |
Description | iFAAM Food labelling |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | 80 stakeholders attended a 1 day iFAAM/ILSI workshop on improving allergen food labelling. Feedback useful in determining ongoing activities. |
Year(s) Of Engagement Activity | 2015 |