Development of a measuring technique based on JET second D-T campaign (DTE2) experience for assessing fusion power at ITER during D-T operation using the radial gamma-ray spectrometer.

The ITER Radial Gamma-Ray Spectrometer (RGRS) consists of three gamma-ray detectors observing the plasma through three collimated, coplanar, radial lines of sight (LoS). The system was initially designed to monitor the runaway electron emission and the alpha-particle density profile [Nocente et al., Nucl. Fusion 57, 076016 (2017)]. This work presents a novel technique for measuring the fusion power during D-T operation using the RGRS. This method is based on the absolute measurement of the 17 MeV fusion gamma-rays and a semi-analytical computation of their transport from the plasma source to the detectors. This approach was initially developed and tested at JET during the second D-T campaign (DTE2) on a single LoS diagnostic [Dal Molin et al., Phys. Rev. Lett. (submitted) (2024); Rebai et al., Phys. Rev. C (submitted) (2024); and Marcer et al., Nucl. Fusion (unpublished) (2024)]. This work exploits the multiple LoS of the RGRS to create a combined virtual diagnostic whose detected fraction of the total plasma emission is less affected by variations in the plasma emission profile, reducing systematic uncertainties on the estimated total emission, compared to the individual detectors.

Conceptual design of a GEM (gas electron multiplier) based gas Cherenkov detector for measurement of 17 MeV gamma rays from T(D, γ)5He in magnetic confinement fusion plasmas.

The only method for assessing the fusion power throughput of a deuterium-tritium (DT) reactor presently relies on determining the absolute number of 14 MeV neutrons produced in the DT plasma. An independent method, developed and investigated during the recent DT campaign at the Joint European Torus, is based on the absolute counting of 17 MeV gamma rays produced by the competing T(D, γ)5He reaction that features a very weak branching ratio (about 3-6 × 10-6) when compared to the main T(D, n)4He reaction. The state-of-the-art spectrometer used for gamma-ray measurements in magnetic confinement fusion plasmas is LaBr3(Ce) scintillator detectors, although they require significant neutron shielding to extract a relatively weak gamma-ray signal from a much more abundant neutron field. A better approach relies on a gamma-ray detector that is intrinsically insensitive to neutrons. We have advanced the design of a gamma-ray counter based on the Cherenkov effect for gamma-rays whose energy exceeds 11 MeV, optimized to work in the neutron-rich environment of a steady-state, magnetically confined fusion plasma device. The gamma-rays interact with an aluminum window and extract electrons that move into the radiator emitting photons via the Cherenkov effect. Since the Cherenkov light consists of few photons (25 on average) in the far UV band (100-200 nm), a pre-amplifier is required to transport the photons to the neutron-shielded location, which may be a few meters away, where the readout elements of the detector, either a silicon or standard photomultiplier tube, are placed. The present work focuses on the development of a scintillating GEM (Gas Electron Multiplier) based pre-amplifier that acts as a Cherenkov photon pre-amplifier and wavelength shifter. This paper presents the result of a set of Garfield++ simulations developed to find the optimal GEM working parameters. A photon gain of 100 is obtained by biasing a single GEM foil to 1 kV.

A high-resolution neutron spectroscopic camera for the SPARC tokamak based on the Jet European Torus deuterium-tritium experience.

Dedicated nuclear diagnostics have been designed, developed, and built within EUROFUSION enhancement programs in the last ten years for installation at the Joint European Torus and capable of operation in high power Deuterium-Tritium (DT) plasmas. The recent DT Experiment campaign, called DTE2, has been successfully carried out in the second half of 2021 and provides a unique opportunity to evaluate the performance of the new nuclear diagnostics and for an understanding of their behavior in the record high 14 MeV neutron yields (up to 4.7 × 1018 n/s) and total number of neutrons (up to 2 × 1019 n) achieved on a tokamak. In this work, we will focus on the 14 MeV high resolution neutron spectrometers based on artificial diamonds which, for the first time, have extensively been used to measure 14 MeV DT neutron spectra with unprecedented energy resolution (Full Width at Half Maximum of ≈1% at 14 MeV). The work will describe their long-term stability and operation over the DTE2 campaign as well as their performance as neutron spectrometers in terms of achieved energy resolution and high rate capability. This important experience will be used to outline the concept of a spectroscopic neutron camera for the SPARC tokamak. The proposed neutron camera will be the first one to feature the dual capability to measure (i) the 2.5 and 14 MeV neutron emissivity profile via the conventional neutron detectors based on liquid or plastics scintillators and (ii) the 14 MeV neutron spectral emission via the use of high-resolution diamond-based spectrometers. The new opportunities opened by the spectroscopic neutron camera to measure plasma parameters will be discussed.

A new dedicated signal processing system for gamma-ray spectrometers in high power deuterium-tritium plasma scenarios in tokamaks.

The most performant deuterium-tritium (DT) plasma discharges realized by the Joint European Torus (JET) tokamak in the recent DT campaign have produced neutron yields on the order of 1018 n/s. At such high neutron yields, gamma-ray spectroscopy measurements with scintillators are challenging as events from the neutron-induced background often dominate over the signal, leading to a significant fraction of pileup events and instability of the photodetector gain along with the consequent degradation of the reconstructed spectrum. Here, we describe the solutions adopted for the tangential lanthanum bromide spectrometer installed at JET. A data acquisition system with free streaming mode digitization capabilities for the entire duration of the discharge has been used to solve dead-time related issues and a data reconstruction code with pileup recovery and photodetector gain drift restoration has been implemented for off-line analysis of the data. This work focuses on the acquired data storage and parsing, with a detailed explanation of the pileup recovery and gain drift restoration algorithms.

Food consumption on campus is associated with meal eating patterns among college students.

This is a cross-sectional analysis of data obtained in the baseline of the Longitudinal Study on the Lifestyle and Health of University Students (n 685) carried out in a public Brazilian university. Food intake was assessed using a 24-h dietary recall. Dietary patterns (DP) for breakfast, lunch and dinner were identified using principal component analysis. Generalised linear models were used to analyse the variables associated with each DP. Three DP were extracted for each meal: breakfast: 'White bread and butter/margarine', 'Coffee and tea' and 'Sausages, whole wheat bread and cheese'; lunch: 'Traditional', 'Western' and 'Vegetarian' and dinner: 'Beans, rice and processed juice', 'White bread and butter/margarine' and 'White meat, eggs and natural juice'. Students who had meals at the campus showed greater adherence to the 'White bread and butter/margarine' (exp (ßadj) = 1·15, 95 % CI 1·11, 1·19) and 'Coffee and tea' (exp (ßadj) = 1·06, 95 % CI 1·02, 1·10) breakfast patterns; 'Western' lunch pattern (exp (ßadj) = 1·04, 95 % CI 1·01, 1·08) and to the 'Beans, rice and processed juice' dinner pattern (exp (ßadj) = 1·10, 95 % CI 1·06, 1·14). Having meals at the campus was associated with lower adherence to the 'Sausages, whole wheat bread and cheese' breakfast pattern (exp (ßadj) = 0·93, 95 % CI 0·89, 0·97), 'Traditional' lunch pattern (exp (ßadj) = 0·96, 95 % CI 0·93, 0·99) and to the 'White bread and butter/margarine' (exp (ßadj) = 0·96, 95 % CI 0·93, 0·99) and 'White meat, eggs and natural juice' (exp (ßadj) = 0·96, 95 % CI 0·93, 0·99) dinner pattern. The food environment at campus may influence students' DP. Recognising meal eating patterns is important to support healthy eating promotion strategies on campus. Adjustments in the University Canteen menu could contribute to healthier eating choices among students.

Allergen Immunotherapy (AIT) in children: a vulnerable population with its own rights and legislation - summary of EMA-initiated multi-stakeholder meeting on Allergen Immunotherapy (AIT) for children, held at Paul-Ehrlich-Institut, Langen, Germany, 16.1.2019.

Concerning development of medicinal products, children belong to a so-called "special population" for which additional legislation applies: Regulation (EC) No 1901/2006 on medicinal products for paediatric use sets up a system of requirements, rewards and incentives to ensure that medicinal products are researched, developed and authorized to meet the therapeutic needs of children. Allergen Immunotherapy (AIT) is believed to contain a strong potential for immunomodulatory effects inducing sustained clinical efficacy after cessation of treatment (disease modifying effect) and thereby may prevent the progression of the atopic march towards asthma manifestation. However, to this day only few data on long-term effects in general exist and even fewer in children. These are predominantly data from open studies, which are strongly influenced in their validity by the known placebo effect of AIT. Furthermore, there are no studies allowing for the conclusion that efficacy in adults are mirrored by a similar efficacy in children and thus, up to now, it is not possible to extrapolate data from adults to children. The Paediatric Committee (PDCO)-European Medicines Agency's (EMA) scientific committee responsible for activities on medicines for children-initiated a Multi-Stakeholder Meeting on AIT for Children held at the Paul-Ehrlich-Institut in Langen, Germany, to provide a platform for discussion and exchange of thoughts to this topic between allergy experts from academia, regulators and AIT-manufacturers. The consented meeting minutes, conclusions and participants are presented.

Neutron measurements at the ELISE neutral beam test facility and implications for neutron based diagnostics at SPIDER.

Along the route to the development of a neutral beam injector for ITER, the Padua based Source for Production of Ion of Deuterium Extracted from Rf plasma (SPIDER) and megavolt ITER injector and concept advancement facilities will make use of neutron diagnostics to quantify the homogeneity of the neutral beam profile by measuring the map of the neutron emission from the beam dump with the close-contact neutron emission surface mapping (CNESM) system. Neutrons are here produced from beam-target reactions between the deuterium beam and the deuterons previously adsorbed in the calorimeter. In order to aid the interpretation of the diagnostic data, a dedicated experiment on neutron emission from beam-target reactions with beam parameters approaching those expected at SPIDER has been performed at the Extraction from a Large Ion Source Experiment (ELISE) neutral beam test facility. The time trace of neutron emission has been measured using a calibrated liquid scintillator detector at increasing power densities on the target. Compared to calculations based on the local mixing model, a systematic discrepancy was observed exceeding the statistical accuracy of the measurements and increasing as a linear function of the power density. The data are used to derive an empirical temperature dependent correction for applications to neutron measurements at SPIDER.

Design of gamma-ray spectrometers optimized for fast particle studies at ITER.

A set of gamma ray spectrometers has been designed for ITER within the Radial Gamma Ray Spectrometer (RGRS) project. The aim of this project is designing a system, integrated with the ITER radial neutron camera, which is able to measure the gamma-rays emitted from the plasma with a good energy resolution (about 1.5% at 4.44 MeV) and at high counting rates (in excess of 1 MHz). The RGRS will be able to operate both in the D phase and in the full-power DT phase and will measure gamma rays from (i) reactions between fast ions, such as α particles, and light impurities and (ii) bremsstrahlung emission generated by runaway electron interactions with both plasma bulk and tokamak walls. The RGRS detectors are arranged in nine lines of sights (able to cover a radial region with r < a/3), each featuring a large LaBr3 scintillator crystal. Due to the high neutron flux and magnetic field, several solutions have been adopted to guarantee a good signal to background ratio and MHz counting rate capabilities. The RGRS is capable to combine space and energy distribution measurements of α particles and runaway electrons, which will help the study of the fast particle physics in a burning plasma.

Development of a new compact gamma-ray spectrometer optimised for runaway electron measurements.

A new compact gamma-ray spectrometer was developed in order to optimise the measurement of bremsstrahlung radiation emitted from runaway electrons in the MeV range. The detector is based on a cerium doped lutetium-yttrium oxyorthosilicate (LYSO:Ce) scintillator coupled to a silicon photomultiplier and is insensitive to magnetic fields. A dedicated electronic board was developed to optimise the signal readout as well as for online control of the device. The detector combines a dynamic range up to 10 MeV with moderate energy non-linearity, counting rate capabilities in excess of 1 MHz, and an energy resolution that extrapolates to a few % in the MeV range, thus meeting the requirements for its application to runaway electron studies by bremsstrahlung measurements in the gamma-ray energy range.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.

Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry.

BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.

EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Current practice of allergy diagnosis and the potential impact of regulation in Europe.

In the European Union (EU), the regulatory framework regarding diagnostic allergen extracts is currently in the process of being implemented at the national level. Due to these regulations, the initial and periodic renewal expenses for the registration of diagnostic allergen extracts may render extract production unprofitable. Consequently, many extracts may be at risk of removal from the market. The current survey, which was conducted by a task force of the European Academy of Allergy and Clinical Immunology, aimed to assess the current practice of allergy diagnosis in Europe. This survey revealed that skin tests continue to be the main diagnostic procedure and are used as the first option in almost two-third of all types of allergic diseases and in 90% of individuals suffering from respiratory allergies. Therefore, there is a need to ensure the availability of high-quality allergen extracts to maintain the common diagnostic procedures used by EU professionals. To reach this goal, it is necessary to align efforts and establish active partnerships between manufacturers, relevant scientific societies, consumer organizations and authorities to maintain the availability of these diagnostic tools.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

PURPOSE: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. METHODS: We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. RESULTS: The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. CONCLUSIONS: Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Health economic analysis of allergen immunotherapy for the management of allergic rhinitis, asthma, food allergy and venom allergy: A systematic overview.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions. METHODS: We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. RESULTS: Twenty-three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20 000/quality-adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost-effective for very high-risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost-effectiveness of AIT for food allergy. CONCLUSIONS: Overall, the evidence to support the cost-effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost-effective for people with allergic rhinitis with or without asthma and in high-risk subgroups for venom allergy. We were unable to draw any conclusions on the cost-effectiveness of AIT for food allergy.