Publications
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Turner P, Fleming L, Saglani S, et al., 2020, Safety of live attenuated influenza vaccine in children with moderate-severe asthma, Journal of Allergy and Clinical Immunology, Vol: 145, Pages: 1157-1164.e6, ISSN: 0091-6749
Background:Live attenuated influenza vaccine (LAIV) is recommended for annual influenza vaccination in children from age 2 years. However, some guidelines recommend against its use in children with asthma or recurrent wheeze due to concerns over its potential to induce wheezing. Objective: To assess the safety of LAIV in children with moderate-severe asthma, and in preschool children with recurrent wheeze. Methods: Prospective, multi-center, open label, phase IV intervention studyin 14 specialist UK clinics.LAIV was administered under medical supervision, with follow-up of asthma symptoms 72 hours and 4 weeks late, using validated questionnaires.Clinical Trials.gov registration NCT02866942, EU Clinical Trials registration 2016-002352-24. Results: 478 young people (median 9.3, range 2–18 years) with physician-diagnosed asthma or recurrent wheeze were recruited, including 208 (44%) prescribed high-dose inhaled corticosteroids and 122 (31%) with severe asthma.There was no significant change in asthma symptoms in the 4 weeks following administration (median change 0, P=.26, McNemar’s test), with no impact of level of baseline asthma control/symptoms in predicting either a worsening of asthma or exacerbation following LAIV using a regression model. 47 subjects (14.7%, 95%CI 11% to 19.1%) reported a severe asthma exacerbation in the four weeks following immunization, requiring short course of systemic corticosteroids; in four cases, this occurred within 72 hours of vaccine. No association with asthma severity, baseline lung function or asthma control was identified.Conclusions: LAIV appears to be well-tolerated in the vast majority of children with asthma or recurrent wheeze, includingthosewhose asthma is categorized as severe or poorly controlled
Hoschler K, Maharjan S, Whitaker H, et al., 2020, Use of traditional serological methods and oral fluids to assess immunogenicity in children aged 2-16 years after successive annual vaccinations with LAIV., Vaccine, Vol: 38, Pages: 2660-2670, ISSN: 0264-410X
BACKGROUND: The UK introduced quadrivalent live attenuated influenza vaccine (qLAIV) for children in 2013/2014. The impact of annual vaccination on effectiveness and immunogenicity is being assessed. METHOD: A phase III/IV open-label study of the immunogenicity of annual vaccination with qLAIV (Fluenz™) was conducted over three consecutive years (2014/15-2016/17) in 254, 249 and 162 children respectively. Serum responses to vaccine components were measured by Haemagglutination Inhibition (HAI) and anti-A(H1N1)pdm09 Neuraminidase (NAI) assays, stratified according to previous receipt of AS03B-adjuvanted A(H1N1)pdm09 pandemic vaccine in 2009/10. Antibody levels to the A(H1N1)pdm09 and H3N2 vaccine components in oral fluids (OF) were explored using an ELISA. FINDINGS: More paired pre- and post-vaccination oral fluids (96%) than paired sera (87%) were obtained. Geometric mean titre rises using HAI assays were limited, with maximum rises seen in year one for both influenza B strains when 39% and 43% of subjects seroconverted (95% confidence interval 33-46% and 36-50%, respectively) and year two for influenza H3N2, when 40% (33-46%) individuals seroconverted. Prior pandemic vaccine receipt resulted in higher pre- and post-vaccination A(H1N1)pdm09 HAI titres and lower pre-and post-vaccination NAI (N1 neuraminidase) titres in all three years. OF results were congruent with HAI results; assay specificity compared to HAI was 88.1 and 71.6 percent, and sensitivity was 86.4 and 74.8 percent respectively for A(H1N1)pdm09 and H3N2. CONCLUSION: In all three study years, vaccination with qLAIV resulted in poor antibody responses. However, OFs are an alternative specimen type that allows self sampling, can easily be obtained from children, and their analysis leads to similar conclusions as classic serology by HAI. Their suitability for seroprevalence studies should be investigated. We demonstrated a sustained effect from prior receipt of the AS03B-adjuvanted A(H1N1)pdm09 vacci
Patel N, Isaacs E, Duca B, et al., 2020, What Dose of Epinephrine? Safety and Pharmacokinetics of 0.5mg versus 0.3mg Epinephrine by Autoinjector in Food-allergic Teenagers: a Randomized Cross-over Trial, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB6-AB6, ISSN: 0091-6749
Patel N, Lindsley S, Vazquez-Ortiz M, et al., 2020, Significant Impact of Screening Challenge on the Improvement in Health-Related Quality of Life During Oral Immunotherapy (OIT), Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB135-AB135, ISSN: 0091-6749
Vereda A, Fernandez-Rivas M, Hourihane JO, et al., 2020, ARTEMIS: A European, Phase 3, Randomised, Double-Blind, Placebo-Controlled Trial of AR101 in Peanut-Allergic Children and Adolescents Aged 4-17, Dermatologie Kompakt & Praxisnah (DKP), Publisher: WILEY, Pages: 8-9, ISSN: 1610-0379
Turner PJ, Regent L, Jones C, et al., 2020, Keeping food-allergic children safe in our schools-Time for urgent action, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 50, Pages: 133-134, ISSN: 0954-7894
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- Citations: 9
Lam CY, Turner P, Jarvis D, 2020, Seasonal trend of food-related anaphylaxis hospital admissions in england, EAACI Congress 2020
Foong RX, Turner P, Fox AT, 2020, Fatal anaphylaxis due to transcutaneous allergen exposure – an exceptional case, Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 332-333, ISSN: 2213-2198
Roberts G, Allen K, Ballmer-Weber B, et al., 2019, Identifying and managing patients at risk of severe allergic reactions to food: report from two iFAAM workshops, Clinical and Experimental Allergy, Vol: 49, Pages: 1558-1566, ISSN: 0954-7894
Food allergy affects a small but important number of children and adults. Much of the morbidity associated with food allergy is driven by the fear of a severe reaction, and fatalities continue to occur. Foods are the commonest cause of anaphylaxis. One of the aims of the European Union funded Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) project was to improve the identification and management of children and adults at risk of experiencing a severe reaction. A number of interconnected studies within the project have focused on quantifying the severity of allergic reactions; the impact of food matrix, immunological factors on severity of reactions; the impact of co‐factors such as medications on the severity of reactions; utilising single dose challenges to understand threshold and severity of reactions; and community studies to understand the experience of patients suffering real‐life allergic reactions to food. Associated studies have examined population thresholds, and co‐factors such as exercise and stress. This paper summarises two workshops focused on the severity of allergic reactions to food. It outlines the related studies being undertaken in the project indicating how they are likely to impact on our ability to identify individuals at risk of severe reactions and improve their management.
Patel N, Vazquez-Ortiz M, Duca B, et al., 2019, Oral immunotherapy using heat-modified peanut in peanut-allergic children in the UK: results from the BOPI (Boiled Peanut Oral Immunotherapy) study, Publisher: WILEY, Pages: 1652-1652, ISSN: 0954-7894
Patel N, Duca B, Isaacs E, et al., 2019, What dose? Pharmacokinetics of two different doses of adrenaline in food-allergic teenagers (The PIMAT Study), Publisher: WILEY, Pages: 1652-1652, ISSN: 0954-7894
du Toit G, Hourihane JO, Beyer K, et al., 2019, ARTEMIS: a European, Phase 3, Randomised, Double-Blind, Placebo-Controlled Trial of AR101 in peanut-allergic children and adolescents aged 4-17 years, Publisher: WILEY, Pages: 1676-1677, ISSN: 0954-7894
Vazquez-Ortiz M, Ludman S, Aston A, et al., 2019, Lip dose challenges in food allergy: current practice and diagnostic utility in the United Kingdom, Journal of Allergy and Clinical Immunology: In Practice, Vol: 7, Pages: 2770-2774.e3, ISSN: 2213-2198
BackgroundLip dose challenges (LDCs) are often performed as an initial step before oral food challenges (OFCs). However, guidance on how to perform and interpret LDCs is unclear, and data are lacking regarding the diagnostic accuracy of LDCs.ObjectiveTo investigate current practice with respect to LDCs among UK allergy health care professionals, and to evaluate the diagnostic utility of LDCs in children undergoing OFCs for IgE-mediated food allergy.MethodsWe used an electronic survey to assess the use of LDCs by UK Allergy clinics. Separately, we prospectively recruited children undergoing “low-risk” OFCs for suspected IgE-mediated food allergy from 2 large specialist allergy units in London. LDC was performed 30 minutes before the OFC, by applying the food to the inner lip for 30 seconds. Objective symptoms were considered a positive outcome. All patients subsequently proceeded to OFC regardless of LDC outcome, and outcome assessed according to PRACTALL consensus.ResultsWe received 147 responses to the online survey, representing 67% of registered pediatric allergy clinics in the United Kingdom. Eighty percent of respondents (representing 81% of responding centers) included LDC as the first step of OFC in routine clinical practice. There was a wide variation in both how LDCs were performed and interpreted, with one-third not proceeding to OFC if LDC resulted in subjective symptoms. In the prospective study, 198 children (mean age, 7 years) with conclusive OFCs were included. Foods tested were tree nuts (30%), peanut (16.6%), egg (16%), fish (10.5%), milk (6%), shrimp (4%), and other (16.9%). There were 12 positive LDCs (1 of which triggered systemic symptoms: generalized urticaria) and 31 positive OFCs. Two children with positive LDCs went on to have a negative diagnostic OFC. Sensitivity of LDC was 32%, specificity 98%, with a false-negative rate of 68%.ConclusionsMost UK allergy clinics included LDC as an initial step during OFC, despite a wide variat
Turner P, 2019, Deriving individual threshold 1 doses from clinical food challenge data for 2 population risk assessment of food allergens, Journal of Allergy and Clinical Immunology, Vol: 144, Pages: 1290-1309, ISSN: 0091-6749
Background: Food allergies are a significant public health issue and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility to limit risks to zero, quantitative allergen risk assessment and management strategies are needed. Objective: To develop appropriate methods for informing population-based risk assessments and risk management programs to benefit all stakeholders, but particularly food allergic individuals. Methods: Individual thresholds for food allergens (maximum tolerable doses and minimum eliciting doses) can ideally be established through double-blind, placebo-controlled food challenges (DBPCFCs). If DBPCFC data is not available, data from widely used “open” food challenges (OFCs) using pre-defined objective criteria can also provide useful data regarding minimum eliciting doses. For more than 20 years, the Netherlands Organisation for Applied Scientific Research (TNO) and The Food Allergy Research and Resource Program (FARRP) at the University of Nebraska-Lincoln have beencollecting individual maximum tolerable doses and minimum eliciting doses that produce objective symptoms from published and unpublished clinical data to better refine knowledge regarding the sensitivity of the population to food allergens. Results: In this paper we provide in depth insights into the methodology applied by TNO and FARRP to derive individual maximum tolerable doses and minimum eliciting doses for objective symptoms from clinical food challenge data. Over 90 examples for determining the individual allergic thresholds are presented. Conclusion: With the methodology presented in this paper, we aim to stimulate harmonization and transparency in quantitative food allergen risk assessment and risk management programs, encouraging their wider adoption.
Turner P, Abdulla AF, Cole M, et al., 2019, Differences in nasal IgA responses to influenza vaccine strains after Live Attenuated Influenza Vaccine (LAIV) immunisation in children, Clinical and Experimental Immunology, Vol: 199, Pages: 109-118, ISSN: 0009-9104
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 immunisation. There was a significant increase in nasal IgA 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 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.
Turner P, 2019, Food allergy desensitisation: a hard nut to crack?, Archives of Disease in Childhood, Vol: 104, Pages: 1021-1022, ISSN: 1468-2044
Worm M, Hanschmann-Mohn T, Scherer Hofmeier K, et al., 2019, Drug-induced anaphylaxis—elicitors, mechanisms and diagnosis, Allergo Journal International, Vol: 28, Pages: 327-329, ISSN: 2197-0378
Drugs are one of the major causes of anaphylaxis. For example 2346 cases of drug-induced anaphylaxis were reported to the anaphylaxis register as of March 2019. The most common triggers of drug-induced anaphylaxis were nonsteroidal anti-inflammatory drugs (NSAIDs; n = 902) and antibiotics (n = 721). Drug-induced anaphylaxis can be caused by IgE-dependent (e.g., penicillins) and IgE-independent mechanisms. Recently MRG-PX2 has been identified as a receptor for non-IgE-dependent mechanisms. Drug-induced anaphylaxis results more frequently in lethal reactions and is more commonly associated with cardiovascular symptoms. Also therapy refractory anaphylaxis is more frequently triggered by drugs. For the diagnosis of drug-induced anaphylaxis current national and international guidelines should be followed including provocation tests to avoid future reactions.
Turner P, Worm M, Ansotegui IJ, et al., 2019, Time to revisit the definition and clinical criteria for anaphylaxis?, The World Allergy Organization Journal, Vol: 12, ISSN: 1939-4551
Anaphylaxis represents the severe end of the spectrum of allergic reactions. A number of different definitions for anaphylaxis are currently foundin the literature (Table 1).[1-6]Manydefine anaphylaxis as a life-threatening reaction. However, data from large case series and patient registries have demonstrated that despite the fact thatthe vast majority of anaphylaxisreactionsare not treated appropriately with prompt administration of epinephrine/adrenaline, ingeneral this does not result in increased mortality or morbidity(such as hospitalization);[7-9]this observation is also consistent with national epidemiological datafor food anaphylaxis, which indicate that fatal anaphylaxis is a rare (but unpredictable) event.[10-12]Therefore, the majority of anaphylaxis reactions cannot be described as life-threatening in themselves,althoughdue to our inability to predict severity of reaction, [12]we emphasise that all anaphylaxis must be appropriately treated with intramuscular epinephrine/adrenaline. Both the descriptions used by the Australasian Society of Clinical Immunology and Allergy (ASCIA)[4] and National Institute of Allergy and Infectious Disease (NIAID)[5] refer to anaphylaxis as a serious allergic reaction, and acknowledge the spectrum of severity in terms of identifying the potential for anaphylaxis to be life-threatening.
Galvin DA, Lindsley S, Patel N, et al., 2019, Validation of food allergy quality of life short forms (FAQLQ-10) for parents, children and teens, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 95-96, ISSN: 0105-4538
Fernandez-Rivas MM, Hourihane JO, Beyer K, et al., 2019, ARTEMIS: A European, phase 3, randomised, double-blind, placebo-controlled trial of AR101 in peanut-allergic children and adolescents aged 4-17, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 16-16, ISSN: 0105-4538
Witmer M, Kearney P, Getts RC, et al., 2019, Predicting eliciting dose at food challenge using epitope mapping in peanut-allergic children, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 152-152, ISSN: 0105-4538
Garcia AO, Bartra J, Garcia RM, et al., 2019, Do threshold data from food challenges reflect real-life allergen exposure?, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 151-151, ISSN: 0105-4538
Patel N, Vazquez-Ortiz M, Abrantes G, et al., 2019, High rate of sustained unresponsiveness in peanut-allergic children undergoing oral immunotherapy using heat-modified peanut: Results from the BOPI study, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 72-72, ISSN: 0105-4538
Abrantes G, Patel N, Lindsley S, et al., 2019, Late and "pseudo-biphasic" anaphylaxis reactions during food challenges to peanut, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 312-312, ISSN: 0105-4538
Verhoeckx K, Bøgh KL, Dupont D, et al., 2019, The relevance of a digestibility evaluation in the allergenicity risk assessment of novel proteins. Opinion of a joint initiative of COST Action ImpARAS and COST Action INFOGEST, Food and Chemical Toxicology, Vol: 129, Pages: 405-423, ISSN: 0278-6915
The current allergenicity assessment of novel proteins is based on the EFSA GMO guidance. Recently, EFSA launched a new guidance document on allergenicity assessment of GM plants (2017). This document describes, amongst other topics, the new scientific and regulatory developments on in vitro protein digestibility tests. The EFSA GMO Panel stated that for in vitro protein digestibility tests, additional investigations are needed before any additional recommendation in the form of guidance can be provided. To this end, an interim phase is considered necessary to evaluate the revisions to the in vitro gastrointestinal digestion test, proposed by EFSA. This prompted the establishment of a joint workshop through two COST Action networks: COST Action ImpARAS and COST Acton INFOGEST. In 2017, a workshop was organised to discuss the relevance of digestion in allergenicity risk assessment and how to potentially improve the current methods and readouts. The outcome of the workshop is that there is no rationale for a clear readout that is predictive for allergenicity and we suggest to omit the digestion test from the allergenicity assessment strategy for now, and put an effort into filling the knowledge gaps as summarized in this paper first.
Patel N, Vazquez-Ortiz M, Turner P, 2019, Risk factors for adverse reactions during OIT, Current Treatment Options in Allergy, Vol: 6, Pages: 164-174, ISSN: 2196-3053
Purpose of reviewOral immunotherapy (OIT) can have a major positive impact on patients with IgE-mediated food allergies, increasing reaction thresholds and reducing the need for dietary and lifestyle limitations. However, patients experience more frequent allergic reactions during OIT than when following dietary avoidance, and 10-75% of patients on OIT may experience anaphylaxis to treatment doses. Our ability to identify patients at higher risk of more severe or frequent reactions during OIT is limited. We review the current data available, and highlight the gaps in knowledge which impede our ability to predict response to treatment, occurrence of dose-related adverse events, and thus acceptance of OIT into wider clinical practice. Recent FindingsOur ability to predict the risk of severe reactions in food-allergic patients is limited, due to the multitude of allergen and host-related factors which influence this. While OIT is thought to reduce this risk, little is known about the immunomodulatory effect of OIT on these factors, and the resulting risk of allergic events during OIT. Several factors have been associated with reaction severity during OIT, and treatment withdrawals, including high allergen-specific IgE levels and certain IgE epitope binding patterns. Other factors proposed include the degree of sensitisation on skin testing, initial reaction threshold, prior reaction severity, age and concomitant allergic disease including allergic rhinitis and asthma. These have also been associated with more severe events in food-allergic patients not undergoing OIT, and suggest a specific patient phenotype prone to more severe and persistent food allergy, which also impact on poorer outcomes during OIT. Ironically, it is this patient phenotype who arguably has most to gain from OIT. SummaryOur understanding of the constellation of factors contributing to reaction threshold, nature and severity in food allergy is improving, and this helps understand the complexity of
Duca B, Patel N, Turner P, 2019, GRADE-ing the benefit/risk equation in food immunotherapy, Current Allergy and Asthma Reports, Vol: 19, ISSN: 1529-7322
Purpose of ReviewWe reviewed the existing evidence base to desensitisation for food allergy, applying the Grading of Recommendations, Assessment, Development and Evaluation approach to discuss whether desensitisation is likely to become part of routine treatment for patients with food allergy.Recent FindingsDesensitisation for food allergy to peanut, egg and cow’s milk is efficacious, but whether such interventions are cost-effective is less clear, due to the issues over a sustained desensitisation effect and the increase in allergic reactions occurring in patients on treatment. Few studies have assessed the change in health-related quality of life associated with treatment, and most have not considered discordance between parent-reported changes in health-related quality of life (HRQL) outcomes compared to those of the patients themselves; none to date have controlled for the improvement in HRQL occurring after initial challenge which will confound outcomes.SummaryThe lack of longer-term safety and cost-effectiveness data, as well as an absence of current consensus in the reporting of patient-relevant outcomes, must be addressed in order to be able to recommend the introduction of desensitisation as a routine treatment in healthcare systems.
Godi A, Panwar K, Haque M, et al., 2019, Durability of the neutralizing antibody response to vaccine and non-vaccine HPV types 7 years following immunization with either Cervarix® or Gardasil® vaccine, Vaccine, Vol: 37, Pages: 2455-2462, ISSN: 0264-410X
Bivalent (Cervarix®) and quadrivalent (Gardasil®) Human Papillomavirus (HPV) vaccines demonstrate remarkable efficacy against the targeted genotypes, HPV16 and HPV18, but also a degree of cross-protection against non-vaccine incorporated genotypes, HPV31 and HPV45. These outcomes seem to be supported by observations that the HPV vaccines induce high titer neutralizing antibodies against vaccine types and lower responses against non-vaccine types. Few data are available on the robustness of the immune response against non-vaccine types. We examined the durability of vaccine and non-vaccine antibody responses in a follow up of a head-to-head study of 12–15 year old girls initially randomized to receive three doses of Cervarix® or Gardasil® vaccine. Neutralizing antibodies against both vaccine and non-vaccine types remained detectable up to 7 years following initial vaccination and a mixed effects model was used to predict the decline in antibody titers over a 15 year period. The decline in vaccine and non-vaccine type neutralizing antibody titers over the study period was estimated to be 30% every 5–7 years, with Cervarix® antibody titers expected to remain 3–4 fold higher than Gardasil® antibody titers over the long term. The antibody decline rates in those with an initial response to non-vaccine types were similar to that of vaccine types and are predicted to remain detectable for many years. Empirical data on the breadth, magnitude, specificity and durability of the immune response elicited by the HPV vaccines contribute to improving the evidence base supporting this important public health intervention. Original trial: ClinicalTrials.gov NCT00956553.
Fox AT, Turner P, Ewan PW, 2019, Towards excellence in paediatric allergy care for all., Clin Exp Allergy, Vol: 49, Pages: 266-268
Patel N, Vazquez-Ortiz M, Robb A, et al., 2019, Successful Desensitisation And Sustained Unresponsiveness Using Modified Peanut: Results From The BOPI Study, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB83-AB83, ISSN: 0091-6749
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