Emergency treatment of peri-operative anaphylaxis: Resuscitation Council UK algorithm for anaesthetists.

Peri-operative anaphylaxis is a rare but potentially catastrophic event which must be considered whenever unexpected and significant cardiovascular or respiratory compromise occurs during anaesthesia. The Resuscitation Council UK algorithm for peri-operative anaphylaxis highlights the importance of early intravenous adrenaline and fluid resuscitation and provides guidance on the treatment of refractory anaphylaxis and immediate follow-up. This algorithm is endorsed by the Royal College of Anaesthetists, Association of Anaesthetists, British Society of Allergy and Clinical Immunology and Clinical Immunology Professional Network of the British Society for Immunology. This document was produced by the Perioperative Allergy Network steering committee in collaboration with the Resuscitation Council UK.

Pre-existing influenza-specific nasal IgA or nasal viral infection does not affect live attenuated influenza vaccine immunogenicity in children.

The United Kingdom has a national immunization programme 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. Because 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 immunoglobulin (Ig)A in children aged 6-14 years. Nasopharyngeal swabs were collected prior to LAIV immunization 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 data set of LAIV shedding from the same individuals, measured by reverse transcription-polymerase chain reaction. 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 upon whether vaccine virus RNA was detectable after immunization. There was no difference in fold change of antibody between individuals with and without an URTI at the time of immunization. Overall, we observed no effect of pre-existing influenza-specific nasal antibody levels on immunogenicity, supporting annual immunization with LAIV in children.

Differences in nasal immunoglobulin A responses to influenza vaccine strains after live attenuated influenza vaccine (LAIV) immunization in children.

Different vaccine strains included in the live attenuated influenza vaccine (LAIV) have variable efficacy. The reasons for this are not clear and may include differences in immunogenicity. We report a Phase IV open-label study on the immunogenicity of a single dose of quadrivalent LAIV (Fluenz™ Tetra) in children during the 2015/16 season, to investigate the antibody responses to different strains. Eligible children were enrolled to receive LAIV; nasal samples were collected before and approximately 4 weeks after immunization. There was a significant increase in nasal immunoglobulin (Ig)A to the H3N2, B/Victoria lineage (B/Brisbane) and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component. The fold change in nasal IgA response was inversely proportional to the baseline nasal IgA titre for H1N1, H3N2 and B/Brisbane. We investigated possible associations that may explain baseline nasal IgA, including age and prior vaccination status, but found different patterns for different antigens, suggesting that the response is multi-factorial. Overall, we observed differences in immune responses to different viral strains included in the vaccine; the reasons for this require further investigation.

Important and specific role for basophils in acute allergic reactions.

IgE-mediated allergic reactions involve the activation of effector cells, predominantly through the high-affinity IgE receptor (FcεRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response. Finally, we examine the potential role of basophils in asthma exacerbations. Understanding the factors that regulate basophil trafficking and activation might lead to new diagnostic and therapeutic strategies in anaphylaxis and asthma.

Logarithmic Upturn in Low-Temperature Electronic Transport as a Signature of d-Wave Order in Cuprate Superconductors.

In cuprate superconductors, high magnetic fields have been used extensively to suppress superconductivity and expose the underlying normal state. Early measurements revealed insulatinglike behavior in underdoped material versus temperature T, in which resistivity increases on cooling with a puzzling log(1/T) form. We instead use microwave measurements of flux-flow resistivity in YBa_{2}Cu_{3}O_{6+y} and Tl_{2}Ba_{2}CuO_{6+δ} to study charge transport deep inside the superconducting phase, in the low-temperature and low-field regime. Here, the transition from metallic low-temperature resistivity (dρ/dT>0) to a log(1/T) upturn persists throughout the superconducting doping range, including a regime at high carrier dopings in which the field-revealed normal-state resistivity is Fermi-liquid-like. The log(1/T) form is thus likely a signature of d-wave superconducting order, and the field-revealed normal state's log(1/T) resistivity may indicate the free-flux-flow regime of a phase-disordered d-wave superconductor.

How does dose impact on the severity of food-induced allergic reactions, and can this improve risk assessment for allergenic foods?: Report from an ILSI Europe Food Allergy Task Force Expert Group and Workshop.

Quantitative risk assessment (QRA) for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments, which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose-response relationship. Emerging data from single-dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single-dose challenges) to reliably identify the effect of dose on severity for use in QRA. Success will reduce uncertainty in the susceptible population and improve consumer choice.

Lifestyle behaviours and perceived well-being in different fire service roles.

BACKGROUND: Aspects of the work environment influence employee well-being. However, it is unclear how employee lifestyle behaviours, health characteristics and well-being may differ within a broader occupational sector. AIMS: To investigate the health characteristics, lifestyle behaviours and well-being of three Fire and Rescue Service (FRS) occupational groups that differ in shift work and occupational demands: operational firefighters (FF), emergency control (EC) and administrative support (AS) workers. METHODS: Data were obtained via an online survey using previously validated questionnaires to assess health characteristics, lifestyle behaviours and perceived well-being. Differences between groups were explored, controlling for confounding variables, using analysis of covariance (ANCOVA) methods. Effect sizes are reported where appropriate to demonstrate clinical significance. RESULTS: Four thousand five hundred and sixty-four FRS personnel volunteered, with 3333 (73%) completing the survey out of a total workforce of 60000 (8%). FF reported the lowest prevalence of chronic medical conditions (10%), compared with AS (21%) and EC (19%) workers. Total physical activity (PA) was 66% higher among FF compared with EC and AS workers. Components of sleep and self-rated health were independent predictors of well-being irrespective of FRS role. CONCLUSIONS: FF reported the highest levels of PA and highest perceptions of well-being, and the lowest prevalence of obesity and chronic medical conditions, compared with other FRS occupational groups. These findings may be used to inform FRS workplace intervention strategies.

Minimal impact of extensive heating of hen's egg and cow's milk in a food matrix on threshold dose-distribution curves.

We analyzed reaction threshold data from 352 children undergoing open food challenges to hen's egg or cow's milk, either fresh or extensively heated into a muffin. There was no significant shift in dose-distribution curves due to the baking process, implying that existing threshold data for these allergens can be applied to allergen risk management, even when these allergens are heat-processed into baked foods.

Can we identify patients at risk of life-threatening allergic reactions to food?

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.

Incidence of food anaphylaxis in people with food allergy: a systematic review and meta-analysis.

BACKGROUND: Food allergy is a common cause of anaphylaxis, but the incidence of anaphylaxis in food allergic people is unknown. METHODS: We undertook a systematic review and meta-analysis, using the inverse variance method. Two authors selected studies by consensus, independently extracted data and assessed study quality using the Newcastle-Ottawa assessment scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS and AMED between January 1946 and September 2012 and recent conference abstracts. We included registries, databases or cohort studies which described the number of food anaphylaxis cases in a defined population and time period and applied an assumed population prevalence of food allergy. RESULTS: We included data from 34 studies. There was high heterogeneity between study results, possibly due to variation in study populations, anaphylaxis definition and data collection methods. In food allergic people, medically coded food anaphylaxis had an incidence rate of 0.14 per 100 person-years (95% CI 0.05, 0.35; range 0.01, 1.28). In sensitivity analysis using different estimated food allergy prevalence, the incidence varied from 0.11 to 0.21 per 100 person-years. At age 0-19, the incidence rate for anaphylaxis in food allergic people was 0.20 (95% CI 0.09, 0.43; range 0.01, 2.55; sensitivity analysis 0.08, 0.39). At age 0-4, an incidence rate of up to 7.00 per 100 person-years has been reported. In food allergic people, hospital admission due to food anaphylaxis had an incidence rate of 0.09 (95% CI 0.01, 0.67; range 0.02, 0.81) per 1000 person-years; 0.20 (95% CI 0.10, 0.43; range 0.04, 2.25) at age 0-19 and 0.50 (0.26, 0.93; range 0.08, 2.82) at age 0-4. CONCLUSION: In food allergic people, the incidence of food allergic reactions which are coded as anaphylaxis by healthcare systems is low at all ages, but appears to be highest in young children.

Dietary management of peanut and tree nut allergy: what exactly should patients avoid?

Peanut and tree nut allergies are the commonest cause of life-threatening food-allergic reactions and significantly affect quality of life in children and their families. Dietary nut avoidance and provision of emergency medication is currently the mainstay of treatment. Nut avoidance has consequences on both quality of life and nutrition. We review the terminology that may cause confusion and lead to unnecessary dietary restrictions. In peanut or tree nut-allergic children, introduction of specific nuts to which the child is not allergic may improve quality of life and should be considered in patients with multiple foods allergies, vegan or ethnic-specific diets, in whom nuts are an important source of protein. Nut-allergic consumers do not just need to avoid foods containing nuts as an ingredient, but also contend with pre-packed foods which frequently have precautionary allergen labelling (PAL) referring to possible nut contamination. Although the published rate of peanut contamination in 'snack' foods with PAL (see Box ) ranges from 0.9-32.4%, peanut contamination in non-snack items with PAL is far less common. We propose that in some peanut-allergic patients (depending on history of reactivity to trace levels of peanut, reaction severity, other medical conditions, willingness to always carry adrenaline, etc.), consideration may be given to allow the consumption of non-snack foods containing PAL following discussion with the patient's (and their family's) specialist. More work is needed to provide consumers with clearer information on the risk of potential nut contamination in pre-packed food. We also draw attention to the change in legislation in December 2014 that require mandatory disclosure of allergens in non-pre-packed foods.

Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial.

BACKGROUND: Previous work has shown patients commonly misuse adrenaline autoinjectors (AAI). It is unclear whether this is due to inadequate training, or poor device design. We undertook a prospective randomized controlled trial to evaluate ability to administer adrenaline using different AAI devices. METHODS: We allocated mothers of food-allergic children prescribed an AAI for the first time to Anapen or EpiPen using a computer-generated randomization list, with optimal training according to manufacturer's instructions. After one year, participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen, JEXT or Auvi-Q), without device-specific training. We assessed ability to deliver adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one year after initial training, and following device switch. Primary outcome was successful adrenaline administration at six weeks, assessed by an independent expert. Secondary outcomes were success at one year, success after switching device, and adverse events. RESULTS: We randomized 158 participants. At six weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%) participants allocated to EpiPen were successful - RR 1.00 (95% CI 0.68-1.46). Success rates at one year were also similar, but digital injection was more common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007). When switched to a new device without specific training, success rates were higher with Auvi-Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001). CONCLUSIONS: AAI device design is a major determinant of successful adrenaline administration. Success rates were low with several devices, but were high using the audio-prompt device Auvi-Q.

Skin testing with raw egg does not predict tolerance to baked egg in egg-allergic children.

BACKGROUND: Most children with egg allergy tolerate egg in baked foods, such as cake, but tolerance cannot be predicted with conventional allergy testing. We hypothesized that the skin prick test (SPT) wheal to unprocessed raw egg might predict tolerance of baked egg at formal oral food challenge (OFC). METHODS: We conducted a retrospective chart review to assess the utility of SPT wheal to egg extract (EE), raw egg (RE), and the ratio of EE:RE in predicting outcome of baked-egg OFC in children presenting to our tertiary referral centers with a physician diagnosis of egg allergy and following complete egg avoidance in their diet, between 2009 and 2013. OFC were performed following a standardized protocol using baked egg in cake, to a total dose equivalent to 3g egg protein. RESULTS: Data were analyzed from 186 completed challenges: OFC was positive in 64 (34%) children and negative in 122 (66%). Six children experienced anaphylaxis at OFC. Children tolerant to baked egg were more likely to have a lower SPT to egg extract/raw egg and EE:RE (median 0.56) than their allergic counterparts (0.70, p < 0.05). However, ROC curve analysis demonstrated poor predictivity of challenge outcome, with AUC for SPT to egg extract, raw egg and EE:ER equal to 0.71, 0.63 and 0.60, respectively. CONCLUSION: EE:RE was not helpful in predicting outcome of baked-egg OFC. Indeed, SPT to egg extract was slightly better at predicting outcome than either SPT to raw egg or EE:RE. Unfortunately, tolerance to baked egg can only be predicted from previous history or through controlled exposure.

Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis.

BACKGROUND: Food allergy is a common cause of anaphylaxis, but the incidence of fatal food anaphylaxis is not known. The aim of this study was to estimate the incidence of fatal food anaphylaxis for people with food allergy and relate this to other mortality risks in the general population. METHODS: We undertook a systematic review and meta-analysis, using the generic inverse variance method. Two authors selected studies by consensus, independently extracted data and assessed the quality of included studies using the Newcastle-Ottawa assessment scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS or AMED, between January 1946 and September 2012, and recent conference abstracts. We included registries, databases or cohort studies which described the number of fatal food anaphylaxis cases in a defined population and time period and applied an assumed population prevalence rate of food allergy. RESULTS: We included data from 13 studies describing 240 fatal food anaphylaxis episodes over an estimated 165 million food-allergic person-years. Study quality was mixed, and there was high heterogeneity between study results, possibly due to variation in food allergy prevalence and data collection methods. In food-allergic people, fatal food anaphylaxis has an incidence rate of 1.81 per million person-years (95%CI 0.94, 3.45; range 0.63, 6.68). In sensitivity analysis with different estimated food allergy prevalence, the incidence varied from 1.35 to 2.71 per million person-years. At age 0-19, the incidence rate is 3.25 (1.73, 6.10; range 0.94, 15.75; sensitivity analysis 1.18-6.13). The incidence of fatal food anaphylaxis in food-allergic people is lower than accidental death in the general European population. CONCLUSION: Fatal food anaphylaxis for a food-allergic person is rarer than accidental death in the general population.

Baked egg food challenges - clinical utility of skin test to baked egg and ovomucoid in children with egg allergy.

BACKGROUND: Many children with IgE-mediated egg allergy can tolerate products containing extensively heated (baked) egg. Aside from food challenge, there are no tests which reliably predict tolerance to baked egg in egg-allergic individuals. OBJECTIVES: To determine if skin prick test (SPT) to baked egg (muffin) and ovomucoid can predict the outcome of baked egg challenges in egg allergic patients. METHODS: In this prospective study, children with a recent history of immediate allergic reactions to egg [and corroborative positive SPT or serum-specific IgE (ssIgE) to egg] or those with SPT/ssIgE > 95% PPV for egg allergy were invited to undergo an open standardized baked egg (muffin) challenge. SPT to egg white, ovomucoid, and fresh muffin were performed immediately prior to challenge. RESULTS: One hundred and forty-three egg allergic children underwent baked egg challenge and of these, 90 (63%) tolerated 1 g of egg protein in a baked muffin. Of the 53 positive challenges, eight (15%) had respiratory and/or cardiovascular symptoms. The median SPT diameters in positive challenges compared with negative challenges were baked muffin - 6.0 mm/4.0 mm and ovomucoid 7.5 mm/5.0 mm respectively. Receiver operating characteristic (ROC) curves were generated for SPT to baked egg and ovomucoid. The area under the curve was 0.68 for baked egg, and 0.67 for ovomucoid. A muffin SPT of < 2 mm had a negative predictive value of 88% and an ovomucoid SPT ≥ 11 mm had a positive predictive value of 100%. CONCLUSIONS AND CLINICAL RELEVANCE: A SPT of < 2 mm to muffin had a high negative predictive value to baked egg challenge. Ovomucoid SPT ≥ 11 mm was very likely to predict a reaction to baked egg. In these children, deferring the challenge would be appropriate.

The risk of Kawasaki disease after pneumococcal conjugate & meningococcal B vaccine in England: A self-controlled case-series analysis.

Kawasaki disease (KD) is an uncommon condition occasionally reported after childhood vaccination. Admissions with a KD-compatible diagnosis identified from a national database in England were linked to immunisation records to investigate the risk after pneumococcal conjugate (PCV) or meningococcal B (MenB) vaccines. Both are given at 2/4/12 months of age but were introduced sequentially, allowing their effects to be separately assessed. A total of 553 linked admissions in 512 individuals were validated as KD. The relative incidence (RI) within 28 days of PCV doses 1 or 2 measured by the self-controlled case-series method was 0.62 (95% confidence interval (CI) 0.38-1.00) with a significantly decreased risk after dose 3 (RI 0.30 (95% CI 0.11-0.77)). For MenB vaccine, the RI after doses 1 or 2 was 1.03 (95% CI 0.51-2.05) and 0.64 (95% CI 0.08-5.26) after dose 3. This study shows no evidence of an increased risk of KD after either vaccine.