Publications
291 results found
Turner PJ, Brown SGA, 2022, Anaphylaxis, Allergy Essentials, Pages: 271-282, ISBN: 9780323931212
Anaphylaxis is a serious, immediate-type systemic hypersensitivity reaction affecting multiple organ systems and characterized at its most severe by bronchospasm, upper airway angioedema, hypotension, and collapse. Lifetime prevalence is estimated to be 0.05% to 2%, but while anaphylaxis can be life-threatening, fatal anaphylaxis is rare. Medication, foods, and insect stings are the commonest triggers. The cornerstones of emergency management are support of the airway and/or ventilation, supine positioning of the patient, epinephrine (adrenaline), and volume expansion. In the community setting, early administration of rescue epinephrine and contact with emergency services are of equal importance. Following an episode of anaphylaxis, prevention of further episodes requires identification of likely trigger(s) and cofactors, optimizing the management of comorbidities, allergen avoidance strategies, and immunotherapy if available. Patient education including an anaphylaxis action plan and an epinephrine autoinjector should be considered where an allergen may be encountered unexpectedly (food and insect sting anaphylaxis, idiopathic anaphylaxis).
Turner PJ, Patel N, Ballmer-Weber BK, et al., 2022, 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, Vol: 10, Pages: 59-70, 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.
Anagnostou A, Sharma V, Herbert L, et al., 2022, Fatal food anaphylaxis: distinguishing fact from fiction., Journal of Allergy and Clinical Immunology: In Practice, Vol: 10, Pages: 11-17, ISSN: 2213-2198
Although there is a general perception that the prevalence of food allergy is increasing, data supporting this are limited. Food is the least common cause of fatal anaphylaxis, and fortunately, it is a very rare event; however, it is also unpredictable. There is widespread consensus that severe reactions cannot be predicted in a clinically meaningful way. Certain food triggers are more frequently associated with fatal anaphylaxis than others. In observational studies, peanut and tree nuts account for at least 30% to 50% of fatalities, with seafood and cow's milk also associated with fatal reactions. Fatal food-induced anaphylaxis is most likely to occur during adolescence and young adulthood, although the reasons for this are unclear. International guidelines agree that intramuscular (IM) epinephrine is the treatment of choice for managing food-triggered anaphylaxis and has a good safety profile when given by the IM route. However, fatalities still occur despite the timely administration of epinephrine. Food-allergic individuals must navigate a world that requires daily vigilance for allergens and preparedness for allergic reactions. Although the actual risk of fatal reactions is minimal, it is not zero, and severe reactions are unpredictable. Clinicians need to help patients better understand the very low but real risk of fatal reaction and enable them to lead as normal a life as possible through appropriate education, safety netting, and risk reduction.
Stuart ASV, Shaw RH, Liu X, et al., 2021, Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial, The Lancet, Vol: 399, Pages: 36-49, ISSN: 0140-6736
BACKGROUND: Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer-BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). METHODS: Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8-12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. FINDINGS: Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8&middo
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, Vol: 148, Pages: 1515-1525.e3, 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.
Turner PJ, d'Art YM, Duca B, 2021, Single-Dose Oral Challenges to Validate Eliciting Doses in Children With Cow's Milk Allergy, Publisher: AMER ACAD PEDIATRICS, Pages: S28-S29, ISSN: 0031-4005
Campbell DE, Turner PJ, Turner P, 2021, Food protein enterocolitis syndrome: underdiagnosed, not treated optimally, ARCHIVES OF DISEASE IN CHILDHOOD, ISSN: 0003-9888
Turner PJ, Muraro A, Roberts G, 2021, Pharmacokinetics of adrenaline autoinjectors., Clinical and Experimental Allergy, Vol: 52, Pages: 18-28, ISSN: 0954-7894
Anaphylaxis is a medical emergency with adrenaline acknowledged as the first line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10 minutes to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants, and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes.
Turner P, 2021, Development and validation of the food allergy severity score, Allergy, Vol: 77, ISSN: 0105-4538
BackgroundThe heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions.MethodsFollowing a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated.ResultsoFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10−6–1.23 × 10−3). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians.ConclusionFASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.
Turner P, Duca B, A SC, et al., 2021, IgE sensitisation predicts threshold but not anaphylaxis during oral food challenges to cow's milk
<jats:p id="p1">Predicting reaction threshold and severity are important to improve themanagement of food allergy, however the determinants of, andrelationship between, these parameters are significant knowledge gaps.Identifying robust predictors could enable the reliablerisk-stratification of food-allergic individuals. In this series ofyoung people with CM-allergy undergoing DBPCFC – the largest reportedin the literature – we did identify any baseline marker which predictedthe occurrence of anaphylaxis at challenge, consistent with existingdata. There is one report of IgE-sensitisation beingpredictive of severity in CM-allergy, however theauthors included non-reactive patients in their analysis whichsignificantly skewed the analyses, resulting in misleading conclusions. IgE-sensitisation in our cohort, particularly tocasein, was predictive of LOAEL. Including an assessment of casein IgEmay therefore be of clinical utility when evaluating patients withCM-allergy in the clinical setting.</jats:p>
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, Vol: 148, Pages: 1307-1315, 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.
Turner P, Larson H, Dube E, et al., 2021, Vaccine hesitancy: drivers and how the allergy community can help, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 3568-3574, 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.
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, Vol: 9, Pages: 3546-3567, 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.
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, Vol: 51, Pages: 1322-1330, 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
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
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, Vol: 9, Pages: 4075-4086, 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
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.
Dodd A, Hughes A, Sargant N, et al., 2021, Evidence update for the treatment of anaphylaxis, Resuscitation, Vol: 163, Pages: 86-96, ISSN: 0300-9572
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
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.
Sargant N, Dodd A, Hughes A, et al., 2021, Refractory anaphylaxis: treatment algorithm, Allergy, Vol: 76, Pages: 1595-1597, ISSN: 0105-4538
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.
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