274 results found
Ruth E, Heraghty F, Flynn N, et al., 2023, No evidence of isotretinoin sensitization in peanut-allergic children: a cross-sectional study., Br J Dermatol, Vol: 189, Pages: 481-482
Greenhawt M, Dribin TE, Abrams EM, et 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.
Turner P, Mamula J, Laktabi J, et al., 2023, How common are allergic reactions during commercial flights? A systematic review and meta-analysis, Journal of Allergy and Clinical Immunology: In Practice, 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.
Turner P, Patel N, Blumchen K, et 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
Turner P, Patel N, Isaacs E, et 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
Turner PJ, Cardona V, 2023, Clinical criteria for anaphylaxis: Comparing apples and pears., World Allergy Organ J, Vol: 16, ISSN: 1939-4551
Pouessel G, Deschildre A, Dribin TE, et 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.
Anagnostou A, Lieberman J, Greenhawt M, et al., 2023, The future of food allergy: Challenging existing paradigms of clinical practice., Allergy, Vol: 78, Pages: 1847-1865
The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into clinical practice with the goal to reduce the need for food challenges and assist physicians in the-often complex-diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.
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.
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.
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
Greenhawt M, Sindher SB, Wang J, et 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
Turner P, 2023, Delabelling penicillin allergy is not rocket science, Archives of Disease in Childhood, Vol: 108, ISSN: 0003-9888
Gold MS, Amarasinghe A, Greenhawt M, et 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.
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
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.
Arasi S, Nurmatov U, Dunn-Galvin A, et 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
Ratcliffe H, Tiley KS, Andrews N, et 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
Anagnostou KA, Lieberman JA, Greenhawt M, et 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>
Turner PJ, Tang MLK, Wood RA, 2023, Food Allergy and Eosinophilic Gastrointestinal Diseases-The Next 10 Years, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 11, Pages: 72-78, ISSN: 2213-2198
Cardona V, Ansotegui IJ, Ebisawa M, et al., 2023, [Erratum : World Allergy Organization Anaphylaxis Guidance 2020 [Japanese Journal of Allergology Vol.70 (2021) No.9 p.1211-1234]]., Arerugi, Vol: 72, ISSN: 0021-4884
Rijavec M, Maver A, Turner PJJ, et al., 2022, Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling, Frontiers in Immunology, Vol: 13, ISSN: 1664-3224
Background: Anaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed.Objective: We sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis.Methods: Bulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to Hymenoptera venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken.Results: 1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling.Conclusion: Our study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis.
Mack DP, Greenhawt M, Turner P, et al., 2022, Information needs of patients considering oral immunotherapy for food allergy, Clinical and Experimental Allergy, Vol: 52, Pages: 1391-1402, ISSN: 0954-7894
While the historic management of food allergy includes avoidance strategies and allergic reaction treatment, oral immunotherapy (OIT) approaches have become more commonly integrated into therapeutic approaches. International guidelines, phase 3 trials and real-world experience have supported the implementation of this procedure. However, OIT is an elective, rarely curative procedure with inherent risks that necessitates an increased degree of health literacy for the patients and families. Families assume the responsibility of amateur health care providers to ensure the daily safe administration of the allergenic food. As such, it is incumbent upon physicians to ensure that families are prepared for this role. A thorough educational and shared decision-making approach is necessary during the counseling and consent process to adequately inform the families. Educated discussion about the efficacy and patient-centred effectiveness, therapeutic alternatives, and family goals is required to align physician and patient expectations. A frank discussion about the struggles, practical challenges, risks and contraindications can help to develop an understanding of the risk mitigation strategies employed to maintain safety. Physicians should develop a proactive approach to educate families about this, at times, burdensome procedure. This educational approach should encourage ongoing support starting prior to consent through the maintenance visits. By preparing families for their unique management role, physicians can help ensure the safe and successful integration of OIT into the therapeutic offering for the management of food allergies.
Turner PJ, Tang M, 2022, UK paediatric allergy services: A glass half full?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 1241-1243, ISSN: 0954-7894
Turner PJ, Patel N, Campbell DE, et al., 2022, Reproducibility of food challenge to cow’s milk: a systematic review with individual participant data meta-analysis, Journal of Allergy and Clinical Immunology, Vol: 150, Pages: 1135-1143.e8, ISSN: 0091-6749
Background: Cow’s milk (CM) is an increasingly common cause of severe allergic reactions, but there is uncertainty with respect to severity of reactions at low level CM exposure, as well as the reproducibility of reaction thresholds. Objective: To undertake an individual participant data (IPD) meta-analysis of studies reporting double-blind, placebo-controlled food challenges (DBPCFC) in CM, to determine the rate of anaphylaxis to low level exposures and the reproducibility of reaction thresholds. Methods: Systematic review and individual participant data (IPD) meta-analysis of studies reporting relevant data. Authors were contacted to provide additional data and/or clarifications as needed. Risk of bias was assessed using the National Institute for Clinical Excellence methodological checklists. Results: 34 studies were included, representing data from over 1000 participants. The cumulative ED01 and ED05 (cumulative doses causing objective symptoms in 1% and 5% of the at-risk allergic population) were 0.3 (95%CI 0.2-0.5) and 2.9 (95%CI 1.6-5.4) mg, respectively. At meta-analysis, 4.8% (95%CI 2.0-10.9%) and 4.8% (95%CI 0.7-27.1%) of individuals reacting to ≤5mg and ≤0.5mg of CM protein (respectively) had anaphylaxis (minimal heterogeneity,I2 =0%). 110 individuals subsequently underwent a repeat DBPCFC: the intra-individual variation in reaction threshold was limited to a ½-log change in 80% (95%CI 65-89%) of participants. Two individuals initially tolerated 5mg CM protein but then reacted to this dose at a subsequent challenge, although neither had anaphylaxis. Conclusions: Around 5% of CM-allergic individuals reacting to an ED01 or ED05 exposure might have anaphylaxis to that dose. This equates to 5 and 24 anaphylaxis events per 10,000 patients exposed to an ED01 or ED05 dose respectively, in the broader CM-allergic population. The vast majority of these anaphylactic reactions would be at the more mild end of the spectrum of anaphylaxis severity
Shaw RH, Liu X, Stuart ASV, et al., 2022, Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial, The Lancet Respiratory Medicine, Vol: 10, Pages: 1049-1060, ISSN: 2213-2600
BACKGROUND: Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca). METHODS: Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020-005085-33). FINDINGS: Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77-89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2-ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second
Turner PJ, Patel N, Makela MJ, et al., 2022, Improving the reporting of allergic adverse events during immunotherapy for food allergy, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 150, Pages: 1242-1244, ISSN: 0091-6749
Turner PJ, Gretzinger M, Patel N, et al., 2022, Updated threshold dose-distribution data for sesame, Allergy, Vol: 77, Pages: 3124-3162, ISSN: 0105-4538
Suprun M, Kearney P, Butler H, et al., 2022, Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope-specific IgE antibody profiling, Allergy, Vol: 77, Pages: 3061-3069, ISSN: 0105-4538
Background: IgE-epitope profiling can accurately diagnose clinical peanut allergy. Objective: We sought to determine whether sequential (linear) epitope-specific IgE (ses-IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double-blind, placebo-controlled food challenges utilizing PRACTALL dosing.Methods: 64 ses-IgE antibodies were quantified in blood samples using a bead-based epitope assay. A pair of ses-IgEs that predicts Cumulative Tolerated Dose (CTD) was determined using regression in 75 subjects from the discovery cohort. This epitope-based predictor was validated on 331 subjects from five independent cohorts (ages 4-25 years). Subjects were grouped based on their predicted values and probabilities of reactions at each CTD threshold were calculated. Results: In discovery, an algorithm using two ses-IgE antibodies was correlated with CTDs (rho=0.61, p<0.05); this correlation was 0.51 (p<0.05) in validation. Using the ses-IgE-based predictor, subjects were assigned into “high”, “moderate”, or “low” dose reactivity groups. On average, subjects in the “high” group were 4 times more likely to tolerate a specific dose, compared to the “low” group. For example, predicted probabilities of tolerating 4, 14, 44 and 144 or 444mg in the “low” group were 92%, 77%, 53%, 29% and 10% compared to 98%, 95%, 94%, 88% and 73% in the “high” group. Conclusions: Accurate predictions of food challenge thresholds are complex due to factors including limited responder sample sizes at each dose and variations in study-specific challenge protocols. Despite these limitations, an epitope-based predictor was able to accurately identify CTDs and may provide a useful surrogate for peanut challenges.
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