209 results found
Liu X, Shaw RH, Stuart ASV, et al., 2021, Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial., The Lancet, Vol: 398, Pages: 856-869, ISSN: 0140-6736
BACKGROUND: Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer-BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. METHODS: Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative a
Dribin TE, Schnadower D, Wang J, et al., 2021, Anaphylaxis knowledge gaps and future research priorities: a consensus report., Journal of Allergy and Clinical Immunology, ISSN: 0091-6749
BACKGROUND: Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. OBJECTIVE: To systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. METHODS: We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: 1) Population Science, 2) Basic & Translational Sciences, 3) Emergency Department Care/Acute Management, and 4) Long-Term Management Strategies & Prevention. Revised statements were incorporated into an anonymous electronic survey and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0-100 scale. RESULTS: The panel generated 98 statements across the four anaphylaxis themes: Population Science (29), Basic & Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies & Prevention (18). Median scores for impact and feasibility ranged from 50.0-95.0 and from 40.0-90.0. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize post-anaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. CONCLUSIONS: We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.
Turner P, Patel N, 2021, Peanut can be used as a reference allergen for hazard characterization in food allergen risk management: A rapid evidence assessment and meta-analysis, Journal of Allergy and Clinical Immunology: In Practice, ISSN: 2213-2198
Regional and national legislation mandates the disclosure of “priority” allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen (“may contain”) labels (PAL) which are frequently ignored by food allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and non-uniformity in the use of PAL by food businesses. One potential solution would be to establish internationally-agreed “reference doses”, below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at low-level allergen exposure.
Turner P, Stafford A, 2021, Improving severity scoring of food-induced allergic reactions: a global “Best-Worst Scaling” exercise, Journal of Allergy and Clinical Immunology: In Practice, ISSN: 2213-2198
BackgroundThere is no current consensus on assigning severity to food-induced allergic reactions, for example to assess the efficacy of allergen immunotherapy. Existing severity scores lack the capability to discriminate between non-anaphylaxis reactions of different severities. Attempts are ongoing to develop a more discriminatory score, which should ideally be data-driven and validated in multiple cohorts.ObjectiveTo undertake an exercise using ‘Best-Worst Scaling’ (BWS) to define a potential ‘gold standard’ against which severity scoring of food-induced allergic reactions can be refined.MethodsWe undertook a global survey to better understand how healthcare professionals rate the severity of food-induced allergic reactions, using BWS methodology. Respondents were given a number of patient case vignettes describing real-world allergic reactions, and asked to select the pair that, in their opinion, reflected the maximum difference in severity. Responses were then modelled and a “preference” score (representing severity) determined for each scenario. Scenarios were also scored using existing published scoring systems, and the scores compared to the BWS score using Spearman’s R correlation and Cohen’s kappa. Given the differences in definitions of anaphylaxis globally, we also evaluated differences in BWS ranking depending on the geographical location of respondents.Results334 complete responses were received, 183 (55%) from Europe and 65 (20%) from North America. Perception of severity of some reactions appeared to be affected by geographical location. The comparison of BWS ranking with current grading systems identified significant issues that varied from one grading system to another, such as prominence to some symptoms e.g. vomiting which skew grading when using scoring systems not designed for food allergy. In general, current scoring systems poorly discriminate against more mild symptoms and often overestimate the
Turner P, 2021, Identifying key priorities for research to protect the consumer with food hypersensitivity: a UK Food Standards Agency Priority Setting Exercise, Clinical and Experimental Allergy, ISSN: 0954-7894
IntroductionFood hypersensitivity (FHS), including food allergy, coeliac disease and food intolerance, is a major public health issue. The Food Standards Agency (FSA), an independent UK Government department working to protect public health and consumers’ wider interests in food, sought to identify research priorities in the area of FHS.MethodsA priority setting exercise was undertaken, using a methodology adapted from the James Lind Alliance—the first such exercise with respect to food hypersensitivity. A UK-wide public consultation was held to identify unanswered research questions. After excluding diagnostics, desensitization treatment and other questions which were out of scope for FSA or where FSA was already commissioning research, 15 indicative questions were identified and prioritized by a range of stakeholders, representing food businesses, patient groups, health care and academia, local authorities and the FSA.Results295 responses were received during the public consultation, which were categorized into 70 sub-questions and used to define 15 key evidence uncertainties (‘indicative questions’) for prioritization. Using the JLA prioritization framework, this resulted in 10 priority uncertainties in evidence, from which 16 research questions were developed. These could be summarized under the following 5 themes: communication of allergens both within the food supply chain and then to the end consumer (ensuring trust in allergen communication); the impact of socio-economic factors on consumers with FHS; drivers of severe reactions; mechanism(s) underlying loss of tolerance in FHS; and the risks posed by novel allergens/processing.DiscussionIn this first research prioritization exercise for food allergy and FHS, key priorities identified to protect the food-allergic public were strategies to help allergic consumers to make confident food choices, prevention of FHS and increasing understanding of socio-economic impacts. Diagnosis and trea
Turner P, 2021, Vaccine hesitancy: drivers and how the allergy community can help, Journal of Allergy and Clinical Immunology: In Practice, ISSN: 2213-2198
Vaccine hesitancy—defined by the World Health Organization (WHO) as a “delay in acceptance or refusal of vaccines despite availability of vaccination services”—is not a recent phenomenon. Historical records indicate that vaccine hesitancy existed by the 18th century in Europe and even resulted in violent riots. The drivers of vaccine hesitancy have evolved over the last 200 years but not, perhaps, as much as one might expect. More problematic are the means by which concerns over vaccine hesitancy are communicated by a new landscape of digital communication, generating what has been described as an “infodemic” in which an overabundance of information—both factual and misinformation—contributes to hesitancy. In this review, we discuss the background and current drivers of vaccine hesitancy and the evidence base for strategies to combat this. We highlight the important role the allergy/immunology community could have in working to mitigate vaccine hesitancy, particularly with respect to the current coronavirus disease 2019 (COVID-19) pandemic.
Padayachee Y, Flicke S, Linton S, et al., 2021, Review: The nose as a route for therapy. Part 2 Immunotherapy, Frontiers in Allergy, Vol: 2, ISSN: 2673-6101
The nose provides a route of access to the body for inhalants and fluids. Unsurprisingly it has a strong immune defense system, with involvement of innate (e.g., epithelial barrier, muco- ciliary clearance, nasal secretions with interferons, lysozyme, nitric oxide) and acquired (e.g., secreted immunoglobulins, lymphocytes) arms. The lattice network of dendritic cells surrounding the nostrils allows rapid uptake and sampling of molecules able to negotiate the epithelial barrier. Despite this many respiratory infections, including SARS-CoV2, are initiated through nasal mucosal contact, and the nasal mucosa is a significant “reservoir” for microbes including Streptococcus pneumoniae, Neisseria meningitidis and SARS -CoV-2. This review includes consideration of the augmentation of immune defense by the nasal application of interferons, then the reduction of unnecessary inflammation and infection by alteration of the nasal microbiome. The nasal mucosa and associated lymphoid tissue (nasopharynx-associated lymphoid tissue, NALT) provides an important site for vaccine delivery, with cold-adapted live influenza strains (LAIV), which replicate intranasally, resulting in an immune response without significant clinical symptoms, being the most successful thus far. Finally, the clever intranasal application of antibodies bispecific for allergens and Intercellular Adhesion Molecule 1 (ICAM-1) as a topical treatment for allergic and RV-induced rhinitis is explained.
Stafford A, Patel N, Turner P, 2021, Anaphylaxis–moving beyond severity…, Journal of Allergy and Clinical Immunology, Vol: 148, Pages: 83-85, ISSN: 0091-6749
Hourihane JO, Byrne AM, Blümchen K, et al., 2021, Ascertainment bias in anaphylaxis safety data of COVID-19 vaccines, The Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 2562-2566, ISSN: 2213-2198
Turner P, Vazquez-Ortiz M, Duca B, et al., 2021, Single-dose oral challenges to validate eliciting doses in children with cow's milk allergy, Pediatric Allergy and Immunology, Vol: 32, Pages: 1056-1065, ISSN: 0905-6157
Background: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. The ED can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED05 values for cow's milk (the dose expected to cause objective allergic symptoms in 5% of the milk‐allergic population) range from 0.5 mg to 13.9 mg cow's milk protein. We undertook a single‐dose challenge study to validate a predicted ED05 for cow's milk of 0.5 mg protein.Methods: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5 mg cow's milk protein (approximately 0.015 mL of fresh cow's milk). Children over 1 year underwent formal challenge to cow's milk to confirm clinical reactivity.Results: 172 children (median age 6.0 (IQR 0.7‐11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7%‐11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis that responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitization that were associated with objective reactivity to the single‐dose challenge using 0.5 mg cow's milk protein.Conclusions: These data support an estimated ED05 for cow's milk of 0.5 mg protein. Values for ED05 above 0.5 mg for cow's milk protein proposed for allergen risk management need to be reviewed.
Greenhawt M, Abrams EM, Shaker M, et al., 2021, The risk of allergic reaction to SARS-CoV-2 vaccines and recommended evaluation and management: a systematic review, meta-analysis, GRADE assessment, and international consensus approach, Journal of Allergy and Clinical Immunology: In Practice, ISSN: 2213-2198
Concerns for anaphylaxis may hamper SARS-CoV-2 immunization efforts. We convened a multi-disciplinary group of international experts in anaphylaxis comprised of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the WHO global coronavirus database, and the grey literature (inception-March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the GRADE approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases/million (n=41,000,000 vaccinations, 95%CI 4.02-15.59; 26 studies, moderate certainty), the prevalence of PEG allergy is 103 cases/million (95%CI 88-120; 2 studies, very low certainty), and the sensitivity for PEG skin testing is poor though specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.
The Resuscitation Council UK has updated its Guideline for healthcare providers on the Emergency treatment of anaphylaxis. As part of this process, an evidence review was undertaken by the Guideline Working Group, using an internationally-accepted approach for adoption, adaptation, and de novo guideline development based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) framework, referred to as GRADE-ADOLOPMENT. A number of significant changes have been made, which will be reflected in the updated Guideline. These include: emphasis on repeating intramuscular adrenaline doses after 5 min if symptoms of anaphylaxis do not resolve; corticosteroids (e.g. hydrocortisone) no longer being routinely recommended for the emergency treatment of anaphylaxis; interventions for reactions which are refractory to initial treatment with adrenaline; a recommendation against the use of antihistamines for the acute management of anaphylaxis; and guidance relating to the duration of observation following anaphylaxis, and timing of discharge.
Shaker M, Turner P, Greenhawt M, 2021, A cost-effectiveness analysis of epinephrine autoinjector risk stratification for patients with food allergy--one epinephrine autoinjector or two?, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 2440-2451.e3, ISSN: 2213-2201
Background:Food-allergic patients are routinely prescribed 2 epinephrine autoinjectors (EAIs). The cost-effectiveness of this strategy is unknown.Objective:To evaluate the cost-effectiveness of routinely prescribing all patients 2 EAI devices versus a risk-stratified approach (2 EAIs prescribed only for patients with a risk factor).Methods:Markov models compared universal versus risk-stratified approaches on the basis of either a previous medical history of anaphylaxis (PMH-ana) or anaphylaxis requiring multiple epinephrine doses (multi-epi). Cohorts of children with peanut allergy were evaluated over an 80-year time horizon from both US and UK societal and health care perspectives. Models assumed prescribing a second EAI provided a baseline 10-fold risk reduction versus anaphylaxis-related fatality and hospitalization. Cost-effectiveness threshold was $100,000/quality-adjusted life-year (QALY).Results:From a US perspective, universal prescription of 2 EAIs to all patients with peanut allergy was not cost-effective in the base case versus risk stratification by PMH-ana. Universal prescription of 2 EAIs was associated with an incremental cost of $10,696,036/QALY versus the PMH-ana strategy, and $17,514,558/QALY versus the multi-epi strategy. However, the universal strategy became cost-effective versus a multi-epi strategy when single EAI costs were less than $80, second epinephrine dose requirements more than 25.5%, anaphylaxis hospitalization costs more than $18,453, annual anaphylaxis risk more than 76.5%, or anaphylaxis hospitalization rate more than 74.9%. From a UK perspective, universally prescribing 2 EAIs was also not cost-effective (incremental cost of $4,132,440/QALY vs PMH-ana and $6,208,227/QALY vs multi-epi) at single device costs more than $18.ConclusionsAt current EAI prices and low rates of needing 2 devices, limiting the second EAIs to patients with PMH-ana is more cost-effective than routinely prescribing 2 EAIs to all patients (particularly in reso
Patel N, Adelman DC, Anagnostou K, et al., 2021, Using data from food challenges to inform management of food-allergic consumers: a systematic review with individual participant data meta-analysis, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 2249-2262.e7, ISSN: 0091-6749
BackgroundEliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown.ObjectiveOur aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge.MethodsWe conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists.ResultsA total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis.ConclusionAround 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose, respectively, in the broader population
Turner P, Patel N, Vazquez-Ortiz M, et al., 2021, Self-administration of adrenaline for anaphylaxis during in-hospital food challenges improves health-related quality of life, Archives of Disease in Childhood, Vol: 106, Pages: 558-563, ISSN: 0003-9888
Objective To assess the impact of anaphylaxis on health-related quality of life (HRQL) and self-efficacy in food-allergic patients undergoing in-hospital food challenge.Design Secondary analysis of a randomised controlled trial.Setting Specialist allergy centre.Patients Peanut-allergic young people aged 8–16 years.Interventions Double-blind, placebo-controlled food challenge to peanut, with HRQL and self-efficacy assessed using validated questionnaire, approximately 2 weeks prior to and 2 weeks after challenge. Where possible, anaphylaxis was treated with self-injected adrenaline (epinephrine).Main outcome measures Change in HRQL and self-efficacy.Results 56 participants had reactions at food challenge, of whom 16 (29%) had anaphylaxis. Overall, there was an improvement in HRQL (mean 2.6 points (95% CI 0.3 to 4.8); p=0.030) and self-efficacy (mean 4.1 points (95% CI 2.4 to 5.9); p<0.0001), independent of whether anaphylaxis occurred. Parents also reported improved HRQL (mean 10.3 points (95% CI 5.9 to 14.7); p<0.0001). We found evidence of discordance between the improvement in HRQL and self-efficacy as reported by young people and that perceived by parents in their child.Conclusions Anaphylaxis at food challenge, followed by self-administration of injected adrenaline, was associated with an increase in HRQL and self-efficacy in young people with peanut allergy. We found no evidence that the occurrence of anaphylaxis had a detrimental effect. Young people should be encouraged to self-administer adrenaline using their autoinjector device to treat anaphylaxis at in-hospital challenge.Trial registration number NCT02149719
Turner P, Ruiz-Garcia M, Patel N, et al., 2021, Delayed symptoms and orthostatic intolerance following peanut challenge, Clinical and Experimental Allergy, Vol: 51, Pages: 696-702, ISSN: 0954-7894
BackgroundClinical reactions to Oral Food Challenge (OFC) in peanut‐allergic individuals have been well‐characterised, but rates and phenotypes of symptom recurrence beyond the first hour after objective symptoms are less well‐characterised.ObjectiveTo evaluate the rate of new‐onset symptoms occurring at least 1 h after stopping OFC in peanut‐allergic children and adults undergoing peanut‐OFC.MethodsWe prospectively collected data relating to adverse events following positive reactions at double‐blind, placebo‐controlled food challenges (DBPCFC) to peanut in children and adults evaluated for eligibility to participate in two clinical trials (NCT02149719, NCT02665793). The trials included people aged 8 to 45 with primary, IgE‐mediated peanut allergy at DBPCFC. The challenge protocol included consumption of a light meal 1 h after reaction.ResultsA total of 121 participants (64 children, 57 adults) had immediate, objective symptoms at DBPCFC, 25 (17 children, 8 adults) with anaphylaxis. Thirty‐three (27%) had progression or recurrence of symptoms ≥ 1 h after objective clinical reaction, of whom 8 developed anaphylaxis. In 23 cases, the onset of new symptoms was associated with consumption of a light meal. In eight cases, symptoms were limited to a symptomatic postural fall in blood pressure noted in preparation for discharge, without any other new features of an allergic reaction.Conclusions & Clinical RelevanceProgressive or new‐onset symptoms ≥1 h following initial allergic reaction at OFC are common and can include orthostatic hypotension. Recurrent symptoms may be temporally associated with food consumption.
Turner P, Patel N, Baseggio Conrado A, 2021, Global patterns in anaphylaxis due to specific foods: a systematic review, Journal of Allergy and Clinical Immunology, ISSN: 0091-6749
BackgroundThere are increasing global data relating to prevalence of food allergy and food-induced anaphylaxis, however this is often based on surrogate measures of sensitization rather than objective symptoms at food challenge. In terms of protecting food-allergic consumers from reactions, there has been no global survey assessing geographical differences in the proportion of anaphylaxis triggered by specific foods.ObjectiveTo identify common triggers for food-induced anaphylaxis, and how these vary from country to country.MethodsSystematic review of relevant reports published between January 2010 and November 2020. Results were reported following PRISMA guidelines. Publications were screened and data extracted by two independent reviewers, and risk of bias assessed.ResultsSixty-five studies (encompassing 41 countries and all 6 regions as defined by the Food & Agriculture Organization of the United Nations) were included. Significant regional variations in the most common triggers of food-anaphylaxis were seen, however, in general there was good agreement between local legislative requirements for allergen disclosure and the commonest allergens for each region/nation.ConclusionsLocal legislation for allergen disclosure generally reflect those allergens commonly responsible for food-anaphylaxis. Cow’s milk and crustacea appear to be cause a higher proportion of anaphylaxis compared to peanut in some regions.
Patel N, Chong KW, Yip AYG, et al., 2021, Use of multiple epinephrine doses in anaphylaxis: A systematic review and meta-analysis, Journal of Allergy and Clinical Immunology, ISSN: 0091-6749
Background:Regulatory bodies recommend that all patients at risk of anaphylaxis be prescribed 2 epinephrine autoinjectors, which they should carry at all times. This is in contrast to some guidelines. The proportion of anaphylaxis reactions that are treated with multiple doses of epinephrine has not been systematically evaluated.Objective:Our aim was to undertake a systematic review and meta-analysis of published studies reporting epinephrine treatment for anaphylaxis in which data relating to the number of doses administered were available.Methods:We searched the Medline, Embase, and Cochrane databases for relevant studies reporting at least 10 anaphylaxis events (due to food or venom) from 1946 until January 2020. Data were extracted in duplicate for the meta-analysis, and the risk of bias was assessed. The study was registered under the PROSPERO identifier CRD42017069109.Results:A total of 86 studies (36,557 anaphylaxis events) met the inclusion criteria (20 of the studies [23%] were prospective studies; 64 [74%] reported reactions in the community, and 22 [26%] included food challenge data). Risk of bias was assessed as low in 50 studies. Overall, 7.7% of anaphylaxis events from any cause (95% CI = 6.4-9.1) were treated with multiple doses of epinephrine. When only epinephrine-treated reactions for which subsequent doses were administered by a health care professional were considered, 11.1% of food-induced reactions (95% CI = 9.4-13.2) and 17.1% of venom-induced reactions (95% CI = 11.3-25.0) were treated with at least 1 epinephrine dose. Heterogeneity was moderate to high in the meta-analyses, but at sensitivity analysis it was not affected by study design or anaphylaxis definition.Conclusion:Around 1 in 10 anaphylaxis reactions are treated with at least 1 dose of epinephrine.
Cole ME, Kundu R, Abdulla AF, et al., 2021, Pre-existing influenza specific nasal IgA or nasal viral infection does not affect live attenuated influenza vaccine immunogenicity in children., Clinical and Experimental Immunology, Vol: 204, Pages: 125-133, ISSN: 0009-9104
The United Kingdom has a national immunisation program which includes annual influenza vaccination in school-aged children, using live attenuated influenza vaccine (LAIV). LAIV is given annually, and it is unclear whether repeat administration can affect immunogenicity. Since LAIV is delivered intranasally, pre-existing local antibody might be important. In this study, we analysed banked samples from a study performed during the 2017/18 influenza season to investigate the role of pre-existing influenza-specific nasal IgA in children aged 6-14 years. Nasopharyngeal swabs were collected prior to LAIV immunisation, to measure pre-existing IgA levels and test for concurrent upper respiratory tract viral infections (URTI). Oral fluid samples were taken at baseline and 21-28 days after LAIV to measure IgG as a surrogate of immunogenicity. Antibody levels at baseline were compared with a pre-existing dataset of LAIV shedding from the same individuals, measured by RT-PCR. There was detectable nasal IgA specific to all four strains in the vaccine at baseline. However, baseline nasal IgA did not correlate with the fold change in IgG response to the vaccine. Baseline nasal IgA also did not have an impact on whether vaccine virus RNA was detectable after immunisation. There was no difference in fold change of antibody between individuals with and without an URTI at the time of immunisation. Overall, we observed no effect of pre-existing influenza specific nasal antibody levels on immunogenicity, supporting annual immunisation with LAIV in children.
Arasi S, Nurmatov U, Dunn-Galvin A, et al., 2021, Consensus on DEfinition of Food Allergy SEverity (DEFASE) an integrated mixed methods systematic review, The World Allergy Organization Journal, Vol: 14, ISSN: 1939-4551
Background and aims: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. Methods: We undertook a mixed-methods systematic review, which involved searching 11 international biomedical databases for published studies from inception to 31 December 2019. Studies were independently screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses and, therefore, narrative synthesis of quantitative and qualitative data was performed. Results: We found 23 studies providing eligible primary data on symptom-specific severity of food allergic reactions, and 31 previously published symptom-severity scoring systems referred to food allergic reactions. There were seven studies which assessed quality-of-life measures in patients (and family members) with different food allergy severity and two studies that investigated the economic burden of food allergy severity. Overall, the quality and the global rating of all included studies were judged as being moderate. Conclusions: There is heterogeneity among severity scoring systems used and even outcomes considered in the context of severity of food allergy. No score has been validated. Our results will be used to inform the development of an international consensus to define the severity of food allergy. Systematic review registration: A protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42020183103 (https://www.crd.yo
Turner P, Boyle R, Baseggio Conrado A, 2021, Food Anaphylaxis in the United Kingdom: an analysis of national data, 1998-2018, BMJ: British Medical Journal, Vol: 372, ISSN: 0959-535X
Objective To describe time trends for hospital admissions due to food anaphylaxis in the United Kingdom over the past 20 years.Design Analysis of national data, 1998-2018.Setting Data relating to hospital admissions for anaphylaxis and deaths, and prescription data for adrenaline autoinjector devices.Participants UK population as a whole and devolved nations (England, Scotland, Wales, and Northern Ireland).Main outcome measures Time trends, age, and sex distributions for hospital admissions for anaphylaxis due to food and non-food triggers, and how these admission rates compare with the case fatality rate (number of fatalities as a proportion of hospital admissions).Results Between 1998 and 2018, 101 891 people were admitted to hospital for anaphylaxis. Of these admissions, 30 700 (30.1%) were coded as due to a food trigger. Food anaphylaxis admissions increased from 1.23 to 4.04 per 100 000 population per year (from 1998 to 2018), an annual increase of 5.7% (95% confidence interval 5.5% to 5.9%, P<0.001). The largest increase in hospital admissions was observed in children younger than 15 years, with an increase from 2.1 to 9.2 admissions per 100 000 population per year (an annual increase of 6.6%, 95% confidence interval 6.3% to 7.0%). For comparison, the annual increase was 5.9% (5.6% to 6.2%) in people aged 15-59 years and 2.1% (1.8% to 3.1%) in those aged 60 years and older. 152 deaths were identified where the fatal event was probably caused by food induced anaphylaxis. The case fatality rate decreased from 0.7% to 0.19% for confirmed fatal food anaphylaxis (rate ratio 0.931, 95% confidence interval 0.904 to 0.959, P<0.001) and to 0.30% for suspected fatal food anaphylaxis (0.970, 0.945 to 0.996, P=0.024). At least 46% (86 of 187, which also includes 35 deaths in 1992-98) of deaths were triggered by peanut or tree nut. Cow’s milk was responsible for 17 of 66 (26%) deaths in school aged children. Over the same time period
Sahiner UM, Layhadi JA, Golebski K, et al., 2021, Innate Lymphoid Cells: The Missing Part Of A Puzzle In Food Allergy., Allergy
Food allergy is an increasingly prevalent disease which is mainly driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5 and IL-13 with infiltration of mast cells, eosinophils and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. They represent a group of lymphocytes that lack specific, recombined antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces ofthe airways, gut and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs towards inflammatory processes and regulatory mechanisms.
Turner PJ, Ansotegui IJ, Campbell DE, et al., 2021, COVID-19 vaccine-associated anaphylaxis: A statement of the World Allergy Organization Anaphylaxis Committee, The World Allergy Organization Journal, Vol: 14, ISSN: 1939-4551
Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Vaccines often cause adverse events; however, the vast majority of adverse events following immunization (AEFI) are a consequence of the vaccine stimulating a protective immune response, and not allergic in etiology. Anaphylaxis as an AEFI is uncommon, occurring at a rate of less than 1 per million doses for most vaccines. However, within the first days of initiating mass vaccination with the Pfizer-BioNTech COVID-19 vaccine BNT162b2, there were reports of anaphylaxis from the UK and USA. More recent data implies an incidence of anaphylaxis closer to 1:125,000 doses with respect to the Pfizer-BioNTech vaccine. In this position paper, we discuss the background to reactions to the current COVID-19 vaccines and relevant steps to mitigate against the risk of anaphylaxis as an AEFI. We propose a global surveillance strategy led by allergists in order to understand the potential risk and generate data to inform evidence-based guidance, and thus provide reassurance to public health bodies and members of the public.
Dodd A, Hughes A, Turner PJ, 2021, Anaphylaxis management - Why are guidelines inconsistent? A rapid review of advanced life support guidelines for cardiac arrest associated with anaphylaxis, RESUSCITATION, Vol: 159, Pages: 165-167, ISSN: 0300-9572
Ruiz-Garcia M, Bartra J, Alvarez O, et al., 2021, Cardiovascular changes during peanut-induced allergic reactions in human subjects, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 633-642, ISSN: 0091-6749
Background: Food allergy is the commonest cause of anaphylaxis. Changes in posture during acute reactions can trigger fatal outcomes, but the impact of allergic reactions on the cardiovascular system in non-fatal reactions remains poorly understood. Objective: To systematically evaluate changes in cardiovascular function during acute allergic reactions to peanut. Methods: Participants underwent double-blind placebo-controlled food challenge topeanut as part of a clinical trial. Changes in hemodynamic parameters (heart rate, stroke volume, blood pressure, peripheral blood flow) and electrocardiogram during food challenges were assessed using continuous monitoring. ClinicalTrials.gov Identifier: NCT02665793 Results: 57 adults (median age 24 (IQR 20-29) years, 53% female) participated; 22 (39%) had anaphylaxis. Acute reactions were associated with significant changes in stroke volume (mean decrease 4.2%, 95%CI 0.8 to 7.6; p=0.03), heart rate (mean increase 11.6%, 95%CI 8.4 to 14.8; p<0.0001) and peripheral blood flow (mean increase 19.7%, 95%CI 10.8 to 28.6; p<0.0001), irrespective of reaction severity. These changes were reproduced at subsequent repeat peanut challenge in 26 participants, and could be reversed with administration of intravenous fluids which resulted in faster resolution of abdominal symptoms. Conclusions: In this first detailed human study of cardiovascular changes during food-allergic reactions, we found evidence for significant fluid redistribution, independent of reaction severity. This provides a sound rationale for optimizing venous return during significant allergic reactions to food. Finally, these data provide a new paradigm for understanding severity in anaphylaxis, where poor outcomes occur due to a failure in compensatory mechanisms.Ruiz-Garcia et al 5 Clinical Implication: Significant changes in cardiovascular function, including decreased stroke volume, occur during peanut-induced allergic reactions in adults irrespective of severit
Krishna MT, Beck S, Gribbin N, et al., 2021, The impact of COVID-19 pandemic on adult and pediatric allergy & immunology services in the UK National Health Service, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 709-722.e2, ISSN: 2213-2198
BACKGROUND: The COVID-19 pandemic imposed multiple restrictions on healthcare services. OBJECTIVE: To investigate the impact of the pandemic on Allergy & Immunology (A&I) services in the UK. METHODS: National survey of all A&I services registered with the Royal College of Physicians and/or British Society for Allergy and Clinical Immunology. The survey covered staffing, facilities, personal protective equipment, appointments & patient review, investigations, treatments and research activity. Weeks commencing 03 Feb'20 (pre-COVID), 06 April'20 and 08'May'20 were used as reference points for the dataset. RESULTS: 99 services participated. There was a reduction in nursing, medical, administrative and allied health professional staff during pandemic; 86% and 92% of A&I services continued to accept non-urgent and urgent referrals respectively during the pandemic. There were changes in immunoglobulin (Ig) dose and infusion regimen in 67% and 14% of adult and pediatric services respectively; 30% discontinued immunoglobulin replacement in some patients. There was a significant (all variables, p≤0.0001) reduction in the following: face-to-face consultations (increase in telephone consultations), initiation of venom immunotherapy, sublingual and subcutaneous injection immunotherapy, anesthetic allergy testing and hospital procedures (food challenges, immunoglobulin and omalizumab, administration); and a significant increase (p≤0.0001) in home therapy for immunoglobulin and omalizumab. Adverse clinical outcomes were reported, but none were serious. CONCLUSION: The pandemic had significant impact on A&I services leading to multiple unplanned pragmatic amendments in service delivery. There is an urgent need for prospective audits and strategic planning in the medium and long term to achieve equitable, safe and standardised healthcare.
Warren CM, Turner PJ, Chinthrajah RS, et al., 2021, Advancing food allergy through epidemiology: understanding and addressing disparities in food allergy management and outcomes, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 110-118, ISSN: 2213-2198
Epidemiological studies have been pivotal in advancing understanding of the etiology of food allergy and in guiding the development of evidence-based guidelines for food allergy prevention and clinical management. In recent years, as research into the population-level distribution and determinants of food allergy has accumulated, data indicate that substantial differences in food allergy outcomes and management exist across racial/ethnic and other socioeconomic strata. This clinical commentary aims to provide a review of existing epidemiological studies and shed valuable light on the disparate burden of food allergy. Emerging methods to quantify environmental exposure and food allergy outcomes are detailed, as are specific areas in which future research is warranted. We also highlight the role that epidemiology plays in advancing health equity and provide a framework as to how it can effectively inform health policy at all phases of the policy cycle-from initial population health assessment to the evaluation and refinement of specific health policies (ie, national guidelines to promote earlier introduction of peanut-containing foods for allergy prevention).
Turner P, Boyle R, Durham S, 2021, Limited effect of intramuscular epinephrine on cardiovascular parameters during peanut-induced anaphylaxis: an observational cohort study, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 527-530.e1, ISSN: 2213-2198
Lam C, Turner P, Hemming D, et al., 2021, Seasonality of food-related anaphylaxis admissions and associations with temperature and pollen levels, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 518-520.e2, ISSN: 2213-2198
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