Imperial College London

Dr Paul Turner

Faculty of MedicineNational Heart & Lung Institute

Reader in Paediatric Allergy & Clinical Immunology
 
 
 
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Contact

 

+44 (0)20 3312 7754p.turner

 
 
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Location

 

Children's Clinical Research FacilityCambridge WingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

293 results found

Dodd A, Turner PJ, Soar J, Savic L, representing the UK Perioperative Allergy Networket al., 2024, Optimising peri-operative anaphylaxis management: end-tidal carbon dioxide monitoring and adrenaline titration: a reply., Anaesthesia

Journal article

Rodríguez Del Río P, Álvaro-Lozano M, Arasi S, Bazire R, Escudero C, Patel N, Sandoval-Ruballos M, Vazquez-Ortiz M, Nowak-Wegrzyn A, Blümchen K, Dunn Galvin A, Deschildre A, Greenhawt M, Schnadt S, Riggioni C, Remington BC, Turner P, Fernandez Rivas Met al., 2024, Evaluation of clinical outcomes of efficacy in food allergen immunotherapy trials, COFAITH EAACI task force., Allergy, Vol: 79, Pages: 793-822

Food allergy is a global public health problem that until recent years lacked any aetiological treatment supported by academy, industry and regulators. Food immunotherapy (AIT) is an evolving treatment option, supported by clinical practice and industry trial data. Recent AIT meta-analyses have highlighted the difficulty in pooling safety and efficacy data from AIT trials, due to secondary heterogeneity in the study. An EAACI task force (CO-FAITH) initiated by the Paediatric Section was created to focus on AIT efficacy outcomes for milk, egg and peanut allergy rather than in trial results. A systematic search and a narrative review of AIT controlled clinical trials and large case series was conducted. A total of 63 manuscripts met inclusion criteria, corresponding to 23, 21 and 22 studies of milk, egg and peanut AIT, respectively. The most common AIT efficacy outcome was desensitization, mostly defined as tolerating a maintenance phase dose, or reaching a particular dose upon successful exit oral food challenge (OFC). However, a large degree of heterogeneity was identified regarding the dose quantity defining this outcome. Sustained unresponsiveness and patient-reported outcomes (e.g. quality of life) were explored less frequently, and to date have been most rigorously described for peanut AIT versus other allergens. Change in allergen threshold assessed by OFC remains the most common efficacy measure, but OFC methods suffer from heterogeneity and methodological disparity. This review has identified multiple heterogeneous outcomes related to measuring the efficacy of AIT. Efforts to better standardize and harmonize which outcomes, and how to measure them must be carried out to help in the clinical development of safe and efficacious food allergy treatments.

Journal article

Mack DP, Dribin TE, Turner PJ, Wasserman RL, Hanna MA, Shaker M, Tang MLK, Rodríguez Del Río P, Sobolewski B, Abrams EM, Anagnostou A, Arasi S, Bajowala S, Bégin P, Cameron SB, Chan ES, Chinthrajah S, Clark AT, Detjen P, du Toit G, Ebisawa M, Elizur A, Factor JM, Greiwe J, O'B Hourihane J, Hughes SW, Jones DH, Muraro A, Nowak-Wegrzyn A, Patel NB, Scurlock AM, Shah AN, Sindher SB, Tilles S, Vickery BP, Wang J, Windom HH, Greenhawt Met al., 2024, Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent., J Allergy Clin Immunol

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Journal article

Turner PJ, Ansotegui IJ, Campbell DE, Cardona V, Carr S, Custovic A, Durham S, Ebisawa M, Geller M, Gonzalez-Estrada A, Greenberger PA, Hossny E, Irani C, Leung ASY, Levin ME, Muraro A, Oppenheimer JJ, Ortega Martell JA, Pouessel G, Rial MJ, Senna G, Tanno LK, Wallace DV, Worm M, Morais-Almeida M, WAO Anaphylaxis Committee and WAO Allergen Immunotherapy Committeeet al., 2024, Updated grading system for systemic allergic reactions: Joint Statement of the World Allergy Organization Anaphylaxis Committee and Allergen Immunotherapy Committee, The World Allergy Organization Journal, Vol: 17, ISSN: 1939-4551

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.

Journal article

Mack DP, Upton J, Patel N, Turner Pet al., 2024, Flex-IT! Applying “platform trials” methodology to immunotherapy for food allergy in research and clinical practice, Journal of Allergy and Clinical Immunology: In Practice, Vol: 12, Pages: 554-561, ISSN: 2213-2198

There is an increasing trend in the management of food allergy toward active treatment using allergen immunotherapy (AIT). Although AIT is efficacious, treatment-related adverse events are common, particularly with oral immunotherapy in those with high levels of allergen-specific IgE sensitization. In clinical practice, these adverse events inevitably create challenges: clinicians and patients routinely face decisions whether to alter the dose itself, the frequency of dosing, and the pace of escalation, or indeed discontinue AIT altogether. Flexibility is therefore needed to adapt treatment, particularly in clinical practice, so that participants are “treated-to-target.” For example, this may entail a significant change in the dosing protocol or even switching from one route of administration to another in response to frequent adverse events. We refer to this approach as flexible immunotherapy. However, there is little evidence to inform clinicians as to what changes to treatment are most likely to result in treatment success. Classical clinical trials rely, by necessity, on relatively rigid updosing protocols. To provide an evidence base to optimize AIT, the food allergy community should adopt adaptive platform trials, where a “master protocol” facilitates more efficient evaluation, including longer-term outcomes of multiple interventions. Within a single clinical trial, participants are able to switch between different treatment arms; interventions can be added or dropped without compromising the integrity of the trial. Developing platform trials for food AIT may initially be costly, but they represent a significant opportunity to grow the evidence base (with respect to both treatment outcomes and biomarker discovery) at scale. In addition, they could help understand longitudinal disease trajectories that are difficult to study in clinical trials for food allergy due to the time needed to demonstrate changes in efficacy. Finally, their adop

Journal article

Turner PJ, Eiwegger T, 2024, Improving "may contain" labels: A call to team up and share data., Allergy

Journal article

Ratcliffe H, Tiley KS, Longet S, Tonry C, Roarty C, Watson C, Amirthalingam G, Vichos I, Morey E, Douglas NL, Marinou S, Plested E, Aley PK, Galiza E, Faust SN, Hughes S, Murray C, Roderick MR, Shackley F, Oddie S, Lee TWR, Turner DPJ, Raman M, Owens S, Turner PJ, Cockerill H, Lopez Bernal J, Ijaz S, Poh J, Shute J, Linley E, Borrow R, Hoschler K, Brown KE, Carroll MW, Klenerman P, Dunachie SJ, Ramsay M, Voysey M, Waterfield T, Snape MDet al., 2023, Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents., iScience, Vol: 26

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.

Journal article

Turner P, Mamula J, Laktabi J, Patel Net al., 2023, How common are allergic reactions during commercial flights? A systematic review and meta-analysis, Journal of Allergy and Clinical Immunology: In Practice, Vol: 11, Pages: 3400-3406.E4, ISSN: 2213-2198

BackgroundGlobal passenger demand for air travel has increased by over 7% annually since 2006, with a strong recovery following the COVID-19 pandemic. Prior to COVID-19, individuals with food allergies reported significant concern and anxiety over the risk of reactions when travelling by air. However, published data of in-flight medical events (IMEs) due to allergic reactions are limited.ObjectiveTo undertake a systematic review with meta-analysis to estimate the incidence of in-flight medical emergencies (IMEs) due to allergic reactions on commercial flights.MethodsWe searched MEDLINE, Embase, PsycINFO, TRANSPORT databases and the Cochrane Register of Controlled Trials for relevant studies reporting IMEs of allergic etiology, published since 1980. Data were extracted in duplicate for meta‐analysis, and risk of bias assessed. Study registration: PROSPERO CRD42022384341.Results17 studies met the inclusion criteria. At meta-analysis, a pooled estimate of 2.2% (95%CI 1.6%-3.1%) of IMEs are coded as being due to allergic reactions. This may be higher in children (3.1%, 95%CI 1.5%-6.7%). The incidence of allergic IMEs at meta-analysis was 0.7 events per million passengers (95%CI 0.4 to 1.1). Reassuringly, the rate of allergic IMEs has been stable over the past 30 years, despite increasing passenger numbers and food allergy prevalence.ConclusionAllergic reactions coded as IMEs during commercial air travel are uncommon, occurring at an incidence around 10-100 times lower than that reported for accidental allergic reactions to food occurring in the community. Despite increasing passenger numbers and food allergy prevalence, the rate of allergic IMEs has not changed over the past 3 decades.

Journal article

Tanno LK, Worm M, Ebisawa M, Ansotegui IJ, Senna G, Fineman S, Geller M, Gonzalez-Estrada A, Campbell DE, Leung A, Muraro A, Levin M, Ortega Martell JA, Caminati M, Kolkhir P, Le Pham D, Darlenski R, Esteban-Gorgojo I, Rial M, Filipovic I, Chiarella SE, Cuervo-Pardo L, Kwong C, Pozo-Beltran CF, Trinh TH, Greenberger PA, Turner PJ, Thong BY-H, Martin B, Cardona V, WAO Anaphylaxis Committee and the WAO Junior Members Steering Groupet al., 2023, Global disparities in availability of epinephrine auto-injectors., World Allergy Organ J, Vol: 16, ISSN: 1939-4551

BACKGROUND: Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis - both acute and preventative - varies by region. METHODS: The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. RESULTS: Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. CONCLUSION: This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.

Journal article

Ruth E, Heraghty F, Flynn N, McGlynn T, Turner PJ, Kelleher M, Byrne A, Hourihane JOet al., 2023, No evidence of isotretinoin sensitization in peanut-allergic children: a cross-sectional study, BRITISH JOURNAL OF DERMATOLOGY, Vol: 189, Pages: 481-482, ISSN: 0007-0963

Journal article

Greenhawt M, Dribin TE, Abrams EM, Shaker M, Chu DK, Golden DB, Akin C, Anagnostou A, ALMuhizi F, Alqurashi W, Arkwright P, Baldwin JL, Banerji A, Bégin P, Ben-Shoshan M, Bernstein J, Bingeman TA, Bindslev-Jensen C, Blumenthal K, Byrne A, Cahil J, Cameron S, Campbell D, Campbell R, Cavender M, Chan ES, Chinthrajah S, Comberiatti P, Eastman JJ, Ellis AK, Fleischer DM, Fox A, Frischmeyer-Guerrerio PA, Gagnon R, Garvey LH, Grayson MH, Clarisse Isabwe GA, Hartog N, Hendron D, Horner CC, O'B Hourihane J, Iglesia E, Kan M, Kaplan B, Katelaris CH, Kim H, Kelso JM, Kahn DA, Lang D, Ledford D, Levin M, Lieberman JA, Loh R, Mack DP, Mazer B, Mody K, Mosnaim G, Munblit D, Mustafa SS, Nanda A, Nathan R, Oppenheimer J, Otani IM, Park M, Pawankar R, Perrett KP, Peter J, Phillips EJ, Picard M, Pitlick M, Ramsey A, Rasmussen TH, Rathkopf MM, Reddy H, Robertson K, Rodriguez Del Rio P, Sample S, Sheshradi A, Shiek J, Sindher SB, Spergel JM, Stone CA, Stukus D, Tang ML, Tracy JM, Turner PJ, Vander Leek TK, Wallace DV, Wang J, Wasserman S, Weldon D, Wolfson AR, Worm M, Yacoub M-Ret al., 2023, Updated guidance regarding the risk ofAllergic reactions to COVID-19 vaccines and recommended evaluation and management: a GRADE assessment, and international consensus approach., Journal of Allergy and Clinical Immunology, Vol: 152, Pages: 309-325, ISSN: 0091-6749

This guidance updates 2021 GRADE recomendations regarding immediate allergic reactions following COVID-19 vaccines and addresses re-vaccinating individuals with 1st dose allergic reactions and allergy testing to determine re-vaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 re-vaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommenations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the UK, and the US formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy, and re-vaccination after a prior immediate allergic reaction. We suggest against >15-minute post-vaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest re-vaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise, in a properly equipped setting. We suggest against pre-medication, split-dosing, or special precautions because of a comorbid allergic history.

Journal article

Turner P, Patel N, Blumchen K, Berkes S, Sampson HA, Beyer Ket al., 2023, Impact of using less objective symptoms to define tolerated dose during food challenges: a data-driven approach, Journal of Allergy and Clinical Immunology, Vol: 152, Pages: 145-154, ISSN: 0091-6749

Background:Food challenges (FCs) form the basis for assessing efficacy outcomes in interventional studies of food allergy; however, different studies have used a variety of similar but not identical criteria to define a challenge reaction, including subjective (nonobjective) symptoms occurring in a single-organ system as dose limiting.Objective:Our aim was to undertake a secondary analysis of 4 interventional studies to assess the impact of using less objective criteria to determine challenge-stop on reaction thresholds and their reproducibility.Methods:We analyzed individual participant data, including individual participant data meta-analysis, by using 3 different published challenge-stop criteria: (1) PRACTALL consesus criteria; (2) Consortium for Food Allergy Research version 3 (CoFAR v3) with at least 1 moderate- or severe-grade symptom; or (3) CoFAR v3 with at least 2 mild symptoms occurring in different organ systems. Reproducibility of challenge threshold was also assessed in participants undergoing subsequent repeat FCs.Results:Four studies, with detailed challenge data from a total of 592 participants, were included. Applying CoFAR v3 definitions for dose-limiting symptoms resulted in an underestimate of reaction thresholds compared with those in PRACTALL (P < .001) that is equivalent to almost a single dosing increment when using a semi-log dosing regimen. Reproducibility was also reduced when applying CoFAR v3 (P < .001 [n = 223]). Using the least conservative interpretation of CoFAR v3 (≥2 mild symptoms occurring in different systems) resulted in a significant overestimate of 15% when assessing oral immunotherapy efficacy. Applying a data-driven minor modification to CoFAR v3 resulted in a new set of challenge-stop criteria with validity similar to that of PRACTALL but one that is simpler to implement and in which significant gastrointestinal discomfort with observable decreased activity remains a dose-limiting symptom.Conclusion:The use of les

Journal article

Turner P, Patel N, Isaacs E, Duca B, Fontanella Set al., 2023, Optimal dose of adrenaline auto-injector for children and young people at risk of anaphylaxis: a phase IV randomised controlled crossover study, Allergy, Vol: 78, Pages: 1997-2006, ISSN: 0105-4538

BackgroundGuidelines recommend intramuscular injection of 500 μg adrenaline (epinephrine) for anaphylaxis in teenagers and adults; however, most autoinjectors deliver a maximum 300 μg dose. We evaluated plasma adrenaline levels and cardiovascular parameters (including cardiac output) following self-injection with 300 μg or 500 μg adrenaline in teenagers at risk of anaphylaxis.MethodsSubjects were recruited to a randomized, single-blind two period crossover trial. Participants received all 3 injections (Emerade® 500 μg, Emerade® 300 μg, Epipen® 0.3 mg) on 2 separate visits (allocated in a randomized block design), at least 28 days apart. Intramuscular injection was confirmed by ultrasound, and heart rate/stroke volume assessed using continuous monitoring. The trial was registered at Clinicaltrials.gov (NCT03366298).ResultsTwelve participants (58% male, median 15.4 years) participated; all completed the study. 500 μg injection resulted in a higher and more prolonged peak concentration (p = 0.01) and greater Area-Under-Curve for plasma adrenaline (p < 0.05) compared to 300 μg, with no difference in adverse events. Adrenaline caused a significant increase in heart rate irrespective of dose and device. Unexpectedly, 300 μg adrenaline resulted in a significant increase in stroke volume when delivered with Emerade®, but a negative inotropic effect with Epipen® (p < 0.05).ConclusionsThese data support a 500 μg dose of adrenaline to treat anaphylaxis in individuals >40 kg in the community. The contrasting effects on stroke volume between Epipen® and Emerade®, despite similar peak plasma adrenaline levels, are unexpected. There is an urgent need to better understand differences in pharmacodynamics following adrenaline administration by autoinjector. In the meantime, we recommend adrenaline injection

Journal article

Pouessel G, Deschildre A, Dribin TE, Ansotegui IJ, Cardona V, Chinthrajah RS, Ebisawa M, Muraro A, Roberts G, Sampson HA, Waserman S, Wood R, Worm M, Turner PJet al., 2023, Refractory anaphylaxis: a new entity for severe anaphylaxis, Journal of Allergy and Clinical Immunology: In Practice, Vol: 11, Pages: 2043-2048, ISSN: 2213-2198

Anaphylaxis reactions lie on a spectrum of severity, ranging from relatively mild lower respiratory involvement (depending on the definition of anaphylaxis used) to more severe reactions which are refractory to initial treatment with epinephrine and may rarely cause death. A variety of grading scales exist to characterize severe reactions, but there is a lack of consensus about the optimal approach to define severity. More recently, a new entity called refractory anaphylaxis (RA) has emerged in the literature, characterized by the persistence of anaphylaxis despite initial epinephrine treatment. However, slightly different definitions have been proposed to date. In this Rostrum, we review these definitions as well as data relating to epidemiology, elicitors, risk factors and management of RA. We propose a need to align the different definitions for RA, to improve epidemiological surveillance, advance our understanding of the pathophysiology of RA, and optimize management strategies to reduce morbidity and mortality.

Journal article

Anagnostou A, Lieberman J, Greenhawt M, Mack DP, Santos AF, Venter C, Stukus D, Turner PJ, Brough HAet al., 2023, The future of food allergy: Challenging existing paradigms of clinical practice, ALLERGY, Vol: 78, Pages: 1847-1865, ISSN: 0105-4538

Journal article

Turner PJ, Cardona V, 2023, Clinical criteria for anaphylaxis: Comparing apples and pears, WORLD ALLERGY ORGANIZATION JOURNAL, Vol: 16, ISSN: 1939-4551

Journal article

Bartra J, Turner P, Munoz-Cano RM, 2023, Cofactors in food anaphylaxis in adults, Annals of Allergy, Asthma, and Immunology, Vol: 130, Pages: 733-740, ISSN: 1081-1206

Around 25% to 50% of food-induced allergic reactions in adults cause anaphylaxis, and epidemiologic evidence suggests that food is the most common cause of anaphylaxis. Reaction severity is unpredictable, and patients will often experience reactions of variable severity, even to an identical exposure (both dose and allergen). A common explanation for this phenomenon has been the impact of “cofactors”—factors that might contribute to reaction severity independent of the allergen exposure. Cofactors can influence reaction severity in 2 ways: either by reducing the reaction threshold (ie, the dose needed to trigger any symptoms) so that patients have no symptoms in the absence of the cofactor and only react with the cofactor present, or by increasing reaction severity such that individuals have only mild symptoms in the absence of the cofactor, but a more severe reaction when the cofactor is present. Indeed, the same patient may have reactions with different cofactors or even need more than one cofactor to develop a severe reaction. Cofactors reportedly play a role in approximately 30% of anaphylaxis reactions in adults. Exercise, nonsteroidal, anti-inflammatory drugs, alcohol, and sleep deprivation are the most frequent cofactors reported. Routine evaluation of the possible involvement of cofactors is essential in managing patients with food anaphylaxis: in patients with a suggestive history but a negative oral food challenge, cofactors should be taken into account to provide appropriate advice to reduce the risk of future anaphylaxis.

Journal article

Turner P, Stafford A, 2023, Grading the severity of anaphylaxis, Current Opinion in Allergy and Clinical Immunology, Vol: 23, Pages: 218-225, ISSN: 1473-6322

Purpose of review Despite no global consensus on a definition of anaphylaxis, there is increasing recognition that just as allergic reactions lie on a spectrum of severity, the same is for anaphylaxis. A variety of severity scores exist in the literature. We review the approaches taken to develop these scores, and their relative advantages and disadvantages.Recent findings There have been four recent comparisons of published severity scores. All have highlighted the heterogeneity between scoring systems, and the lack of transferability from one approach to another. Notably, only one score has been developed using a data-driven approach, and none has undergone formal and comprehensive validation.Summary It is unclear whether a single severity score is achievable, or indeed desirable. If the aim is to guide management of acute reactions, then assignment of severity is not only unnecessary but might delay treatment and cause harm. Severity scores are needed in the research setting, but require an approach which can discriminate between reactions of similar but nonidentical severity (particularly, nonanaphylaxis reactions). Any approach should be fit for purpose, informed by patient and clinician experience, and ideally be data-driven to minimize subjective bias and facilitate objective validation.

Journal article

Turner P, 2023, Persistence of immune response in heterologous COVID vaccination schedules in the Com-COV2 study - a single-blind, randomised trial incorporating mRNA, viral-vector and protein-adjuvant vaccines, Journal of Infection, Vol: 86, Pages: 574-583, ISSN: 0163-4453

BackgroundHeterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development.MethodsCom-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose ‘ChAd’ (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or ‘BNT’ (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8–12 weeks later with either the homologous vaccine, or ‘Mod’ (mRNA-1273, Spikevax, Moderna) or ‘NVX’ (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration.FindingsIn April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N = 540, 45% female) or BNT (N = 532, 39% female) as part of the national vaccination programme.In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95% CI (confidence interval): 8.2, 11.5) at D28 to 6.2 (95% CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95% CI:2.5,3.5) to 2.4 (95% CI:1.9, 3.0).In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The adjusted GMR (aGMR) for BNT/Mod compared with BNT/BNT increased from 1.36 (95% CI: 1.17, 1.58) at D28 to 1.52 (95

Journal article

Turner PJ, 2023, Global Patterns in Food-Induced Anaphylaxis, Publisher: WILEY, Pages: S68-S69, ISSN: 8755-6863

Conference paper

Greenhawt M, Sindher SB, Wang J, O'Sullivan M, du Toit G, Kim EH, Albright D, Anvari S, Arends N, Arkwright PD, Bégin P, Blumchen K, Bourrier T, Brown-Whitehorn T, Cassell H, Chan ES, Ciaccio CE, Deschildre A, Divaret-Chauveau A, Dorris SL, Dorsey MJ, Eiwegger T, Erlewyn-Lajeunesse M, Fleischer DM, Ford LS, Garcia-Lloret M, Giovannini-Chami L, Hourihane JO, Jay N, Jones SM, Kerns LA, Kloepfer KM, Leonard S, Lezmi G, Lieberman JA, Lomas J, Makhija M, Parrish C, Peake J, Perrett KP, Petroni D, Pfützner W, Pongracic JA, Quinn P, Robison RG, Sanders G, Schneider L, Sharma HP, Trujillo J, Turner PJ, Tuttle K, Upton JE, Varshney P, Vickery BP, Vogelberg C, Wainstein B, Wood RA, Bee KJ, Campbell DE, Green TD, Rouissi R, Peillon A, Bahnson HT, Bois T, Sampson HA, Burks AWet al., 2023, Phase 3 Trial of epicutaneous immunotherapy in toddlers with peanut allergy., New England Journal of Medicine, Vol: 388, Pages: 1755-1766, ISSN: 0028-4793

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut al

Journal article

Turner P, 2023, Delabelling penicillin allergy is not rocket science, Archives of Disease in Childhood, Vol: 108, ISSN: 0003-9888

Journal article

Gold MS, Amarasinghe A, Greenhawt M, Kelso JM, Kochhar S, Yu-Hor Thong B, Top KA, Turner PJ, Worm M, Law Bet al., 2023, Anaphylaxis: Revision of the Brighton collaboration case definition, Vaccine, Vol: 41, Pages: 2605-2614, ISSN: 0264-410X

The Brighton Collaboration (BC) has formulated a number of case definitions which have primarily been applied to adverse events of special interest in the context of vaccine safety surveillance. This is a revision of the 2007 BC case definition for anaphylaxis. Recently, the BC definition has been widely used for evaluating reports of suspected anaphylaxis following COVID-19 vaccination. This has led to debate about the performance of the BC definition in comparison with those from the US National Institute of Allergy and Infectious Disease/Food Allergy Anaphylaxis Network (NIAID/FAAN) and the World Allergy Organization (WAO). BC convened an expert working group to revise the case definition based on their usual process of literature review and expert consensus. This manuscript presents the outcome of this process and proposes a revised case definition for anaphylaxis. Major and minor criteria have been re-evaluated with an emphasis on the reporting of observable clinical signs, rather than subjective symptoms, and a clearer approach to the ascertainment of levels of certainty is provided. The BC case definition has also been aligned with other contemporary and international case definitions for anaphylaxis.

Journal article

Turner P, Warner JO, 2023, Cough up, time's up: pholcodine and risk of anaphylaxis to general anaesthetics., Archives of Disease in Childhood, ISSN: 0003-9888

Journal article

Dribin TE, Waserman S, Turner P, 2023, Who needs epinephrine? Anaphylaxis, auto-injectors, and parachutes, Journal of Allergy and Clinical Immunology: In Practice, Vol: 11, Pages: 1036-1046, ISSN: 2213-2198

International guidelines stipulate that intramuscular (IM) epinephrine (adrenaline) is the first-line treatment for anaphylaxis, with an established good safety profile. The availability of epinephrine autoinjectors (EAI) has greatly facilitated the lay administration of IM epinephrine in community settings. However, key areas of uncertainty remain around epinephrine usage. These include variations in prescribing EAI, what symptoms should prompt epinephrine administration, whether emergency medical services (EMS) need to be contacted after administration, and whether epinephrine administered via EAI reduces mortality from anaphylaxis or improves quality of life measures. We provide a balanced commentary on these issues. There is increasing recognition that a poor response to epinephrine, particularly after 2 doses, is a useful marker of severity and the need for urgent escalation. It is likely that patients who respond to a single epinephrine dose do not require EMS activation or emergency department transfer, but data are needed to demonstrate the safety of this approach. Lastly, patients at risk of anaphylaxis must be counseled against over-reliance on EAI alone.

Journal article

Arasi S, Nurmatov U, Dunn-Galvin A, Roberts G, Turner PJ, Shinder SB, Gupta R, Eigenmann P, Nowak-Wegrzyn A, Ansotegui IJ, Rivas MF, Petrou S, Tanno LK, Vazquez-Ortiz M, Vickery B, Wong G, Alvaro-Lozano M, Asaria M, Begin P, Bozzola M, Boyle R, Brough H, Cardona V, Chinthrajah RS, Cianferoni A, Deschildre A, Fleischer D, Gazzani F, Gerdts J, Giannetti M, Greenhawt M, Guzmán MA, Hossny E, Kauppi P, Jones C, Lucidi F, Monge Ortega OP, Munblit D, Muraro A, Pajno G, Podestà M, Rodriguez Del Rio P, Said M, Santos A, Shaker M, Szajewska H, Venter C, Warren C, Winders T, Ebisawa M, Fiocchi Aet al., 2023, WAO consensus on DEfinition of Food Allergy SEverity (DEFASE)., The World Allergy Organization Journal, Vol: 16, Pages: 1-23, ISSN: 1939-4551

BACKGROUND: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. AIM: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. METHODS PHASE 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. PHASE 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. RESULTS: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. CONCLUSIONS: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an

Journal article

Foong R-X, Patel NB, Turner P, Roberts GC, Fox ATet al., 2023, Preventing food allergy fatalities, ARCHIVES OF DISEASE IN CHILDHOOD, ISSN: 0003-9888

Journal article

Ratcliffe H, Tiley KS, Andrews N, Amirthalingam G, Vichos I, Morey E, Douglas NL, Marinou S, Plested E, Aley P, Galiza EP, Faust SN, Hughes S, Murray CS, Roderick M, Shackley F, Oddie SJ, Lees T, Turner DPJ, Raman M, Owens S, Turner P, Cockerill H, Lopez Bernal J, Linley E, Borrow R, Brown K, Ramsay ME, Voysey M, Snape MDet al., 2023, Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019–2021, Archives of Disease in Childhood, Vol: 108, Pages: 123-130, ISSN: 0003-9888

Objective To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation.Design We conducted a community-based cross-sectional seroprevalence study in participants aged 0–18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region.Results Post-first wave (June–August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10–14 years old) to 9.5% (participants 5–9 years old). By April–June 2021, this had increased to 19.9%, varying from 13.9% (participants 0–4 years old) to 32.7% (participants 15–18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit.Conclusions Approximately one-third of participants aged 15–18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children.Trial registration number NCT0

Journal article

Anagnostou KA, Lieberman JA, Greenhawt M, Mack D, Santos A, Venter C, Stukus D, Turner P, Brough HAet al., 2023, The Future of Food Allergy: Challenging Existing Paradigms of Clinical Practice.

<jats:p id="p1">The field of food allergy has seen tremendous change over the past 5-10years with seminal studies redefining our approach to prevention andmanagement and novel testing modalities in the horizon. Earlyintroduction of allergenic foods is now recommended, challenging theprevious paradigm of restrictive avoidance. The management of foodallergy has shifted from a passive avoidance approach to activeinterventions that aim to provide protection from accidental exposures,decrease allergic reaction severity and improve the quality of life offood-allergic patients and their families. Additionally, noveldiagnostic tools are making their way into the clinical practice withthe goal to reduce the need for food challenges and assist physicians inthe – often complex – diagnostic process. With all the newdevelopments and available choices for diagnosis, prevention andtherapy, shared decision-making has become a key part of the medicalconsultation, enabling patients to make the right choice for them, basedon their values and preferences. Communication with patients has alsobecome more complex over time, as patients are seeking advice online andthrough social media, but the information found online may be outdated,incorrect, or lacking in context. The role of the allergist has evolvedto embrace all the above exciting developments and provide patients withthe optimal care that fits their needs. In this review, we discussrecent developments, as well as the evolution of the field of foodallergy in the next decade.</jats:p>

Journal article

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