Background Many adolescents with asthma have dysfunctional breathing and poor quality of life. Breathing retraining is recommended for symptom management and breathing efficiency. This trial evaluated the feasibility of conducting a definitive trial to evaluate the effectiveness and cost-effectiveness of a digital breathing retraining intervention for adolescents with asthma (Breathe4T – a mobile-friendly website). Specifically, recruitment, follow-up response rates, acceptability and uptake of the intervention and measures, as well as agreement between two quality of life questionnaires were measured. Methods Adolescents (12-17 years) with asthma and impaired quality of life were recruited via UK primary and secondary care clinics and randomised into two, unblinded groups. The intervention group accessed Breathe4T for 6 months whilst the control group gained access after 6 months. Measures included quality of life (paediatric asthma quality of life questionnaire and paediatric quality of life short form), asthma control (asthma control test), healthcare utilisation and demographics at baseline, 2 and 6 months. Website data and interviews explored experiences of the intervention. Results 64 adolescents were randomised. At 2 months 30.2% of participants returned data, however telephone calls improved the rate to 70.3% at 6-month follow-up Breathing retraining was acceptable to adolescents and was perceived to have various benefits. Conclusions The study demonstrates acceptability and feasibility of a future definitive trial to evaluate effectiveness and impacts of a breathing retraining website on quality of life. Implications for recruitment and maximising follow up rates were identified. These learnings are likely to be applicable to other adolescent studies.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization and natural history review. Numerous factors that may affect disease activity and patient wellbeing need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even ‘real-time’, monitoring between visits. Following an approach that included needs assessment, evidence appraisal and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Abstract: Background: The European Academy of Allergy and Clinical Immunology’s (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. Methods: We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 st October 2012 and 30 th June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full-texts, and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta analyses were undertaken for food-test combination where 3 or more studies were available. Results: 149 studies comprising 24,489 patients met the inclusion criteria and were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% undertaken in Europe, ≥95% conducted in a specialized pediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% DBPCFC. Skin prick test (SPT) with fresh cow’s milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE to individual components had high specificity: Ara h 2 had 92%, Cor a 14 95%, Ana o 3 94%, casein 93%, ovomucoid 92/91% for the diagnosis of peanut, hazelnut, cashew, cow’s milk and raw/cooked egg allergies, respectively. BAT was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. Conclusions: SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies. PROSPERO registration: CRD42021259186 Funding: European Academy of Allergy (EAACI).

Adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI. We herein summarize practical resources to support this guideline’s implementation in clinical practice. For this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality, and were pragmatically rated for their evidence-basis and user friendliness. Resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace, and wider community. Most resources were in English, web-based and had limited evidence-basis. This position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care.

Recent reports indiciate that the prevelance of food allergy is increasing, but accurate estimates remain a challenge due to cross-reactivity and limited use of precise diagnostic methods. Component-resolved diagnostics (CRD), in which sensitization to individual molecular components of whole food allergen extracts is measured, is emerging as a promising tool for evaluation of sensitization profiles. In this systematic review, we summarized estimates of prevalence of sensitization to food allergen components in the general population in Europe. We searched seven databases with no restrictions on publication date or language. Two reviewers independently screened the literature and appraised the risk of bias in the included studies. From 4,776 de-duplicated records, five studies, with low to moderate overall risk of bias, were included and narratively synthesized. Forty-six components from 18 foods were investigated. Overall, the prevalence of sensitization was low, particularly for major allergens, and non-existent for 10 components (0% [95% CI 0-0.8]). The highest prevalence was seen for PR-10 proteins, such as Cor a 1.04 (13.6% [95% CI 10.9-16.9]). There were not enough studies to discern regional differences or perfom meta-analysis, highlighting the need for more population-representative studies in order to elucidate patterns of sensitization to food allergen components in Europe.

To the EditorReply to Stefano Miceli SopoFirst of all we want to thank for giving us an opportunity to reply to this correspondence (1), acknowledging the correspondence authors important point about the recommendation of introducing well-cooked, but not raw or uncooked pasteurized hen’s egg as part of complementary feeding.We agree that the evidence-base is sparse, with just two trials about cooked egg contributing to the low to moderate certainty evidence in our review (2) and guideline (3). These studies were in different populations (4, 5). We highlighted these points in the guideline, and the subgroup analysis from the Perkin study (6) was used only as supporting material, and for estimating the amount of egg that could be used. It is correct that the Natsume study included infant at higher risk due to eczema, but that was the case for both groups, and outcome was assessed by controlled challenges as described in the systematic review (2).As set out in the guideline, the process took into account expert insight weighing up benefits and harms, costs, feasibility, standard practice and patient preferences, in addition to published evidence. Weighing up all of these factors, the task force decided that the potential benefits outweighed potential harms in the case of well-cooked egg. One relatively large study found a 29% absolute decrease in the proportion of high risk infants with egg allergy at 1 year when very small amounts of egg were introduced (RR 0.22, 95% CI 0.08 to 0.54) (4). And two trials found no adverse effects (4, 5). It is likely feasible for many families to introduce well-cooked egg as part of complementary feeding, including in baked goods. The potential benefits do not outweigh the harms for uncooked egg, so the task force did not suggest trying this approach.The task force included representatives from many countries and specialties, and followed a robust process when reviewing evidence and debating potential recommendations. As the correspondence authors note, this recommendation is in line with other key guidelines. Whilst the correspondence authors may not agree with specific recommendations, the process used to debate and vote on them was systematic and took into account perspectives from across the world, including those from organisations representing patients and their families. Furthermore, a public consultation process sought feedback prior to publication, which further reinforced consensus about this recommendation.As is the case with all guidelines, the EAACI food allergy prevention guideline provides suggestions for clinicians to consider, alongside the needs of individual patients and local contexts and customs. The guideline is not prescriptive and does not override clinical judgement ad individual circumstances. Given the lack of likely harm, the convenience of this approach and best available evidence to date, the task force stands by its suggestion that clinicians in countries where egg allergy is an issue discuss with families the potential and desire to introduce small amounts of well-cooked egg into the infant diet when appropriate as part of complementary feeding. This need not be from the beginning of complementary therapy and the amounts may be very small.The guideline suggests half of a well-cooked, small egg twice a week, which may be in the form of a hard-boiled egg, well-cooked egg pasta, bread or baked goods, for example (p. 850). There is no evidence of significant harm, and it is likely that infants in many parts of the world may be exposed to egg in their diet anyway. There is no need to avoid this to prevent egg allergy, and in the opinion of the EAACI task force, introducing it may have benefits.Susanne Halken, Professor a, ProfessorAntonella Maria Muraro b, ProfessorGraham Roberts c, ProfessorDebra de Silva d, ProfessorOn behalf of On behalf of the EAACI Prevention Guideline Task Forcea Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, DenmarkbDepartment of Women and Child Health, Food Allergy Referral Centre Veneto Region, Padua University Hospital, Padua, Italyc Clinical and Experimental Sciences and Human Development in Health, Faculty of Medicine, University of Southampton, Southampton, UK. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UKdThe Evidence Centre Ltd, London, UKReferencesStefano Miceli Sopo, Dario Sinatti, Francesco Mastellone, Giulia Bersani, Mariannita Gelsomino. Comment on Halken et al. Pediatr Allergy Immunol . 2022de Silva D, Halken S, Singh C, et al. Preventing food allergy in infancy and childhood: systematic review of randomised controlled trials. Pediatr Allergy Immunol . 2020;31(7):813-826Halken S, Muraro A, de Silva D, et al. EAACI guideline: Preventing the development of food allergy in infants and young children (2020 update). Pediatr Allergy Immunol. 2021;32(5):843-858.Natsume O, Kabashima S, Nakazato J, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 92 2017;389(10066):276-286.Perkin MR, Logan K, Tseng A, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374(18):1733-1743.Perkin MR, Logan K, Bahnson HT, et al. Efficacy of the enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy. J Allergy Clin Immunol. 2019;144(6):1606-1614.

Background There is substantial interest in allergen-specific immunotherapy in food allergy. We systematically reviewed its efficacy and safety. Methods We searched six bibliographic databases from 1946 to 30 April 2021 for randomised controlled trials about immunotherapy alone or with biologicals in IgE-mediated food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. Results We included 36 trials with 2,126 participants, mainly children. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5. to 21.4, high certainty); cow’s milk (RR 5.7, 1.9 to 16.7, moderate certainty) and hen’s egg allergy (RR 8.9, 4.4 to 18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300mg or 1000mg peanut protein was 2. In peanut allergy, oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0 to 1.2, low certainty) or severe reactions (RR 1,6, 0.7 to 3.5, low certainty). It may increase adverse reactions in cow’s milk (RR 3.9, 2.1 to 7.5, low certainty) and hen’s egg allergy (RR 7.0, 2.4 to 19.8, moderate certainty), but reactions tended to be mild and gastrointestinal. Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8 to 3.8, moderate certainty). Results were unclear for other allergies and administration routes. Conclusions Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow’s milk and hen’s egg allergy. However, our review found little about whether this improves quality of life, is sustained or cost-effective.

Background Biological therapies relieve symptoms in allergic and inflammatory diseases so may also benefit people with IgE-mediated food allergy. We systematically reviewed the highest quality published evidence to inform forthcoming GA 2LEN guidelines. Methods We searched six bibliographic databases from 1946 to 30 September 2021 for randomised controlled trials, controlled clinical trials and quasi-randomised trials about biological monotherapy in people with IgE-mediated food allergy confirmed by oral food challenge. We found 3 trials with 118 participants. We used the GRADE approach. We summarised the findings narratively because studies were too heterogeneous to conduct meta-analysis. Results We included one randomised trial about etokimab, one about omalizumab and one about the discontinued TNX-901. All were in people with peanut allergy in the USA, mostly aged 13+ years. There were trends towards improved tolerance of peanut during treatment, with no increase in adverse events compared to placebo. However, we have very low certainty about the evidence. No trial reported on quality of life or cost-effectiveness. Conclusions Our review of the highest quality research found that there is not yet enough certainty of evidence to support offering etokimab or omalizumab widely for food allergy. Clinicians may consider the merits for individuals, but large randomised trials with standardised measures need to confirm the safety and efficacy and the most suitable candidates, doses and durations of treatment.

Medical Algorithm: Early Introduction of Food Allergens in High Risk PopulationsHelen R Fisher,1,2 Gideon Lack,1,2,3 Graham Roberts,4,5,6 Henry T Bahnson,7 George Du Toit.1,2,31Paediatric Allergy Group, Department of Women and Children’s Heath, School of Life Course Sciences, King’s College London, London, United Kingdom2Paediatric Allergy Group, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom.3Children’s Allergy Service, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom.4The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UK.5NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.6Faculty of Medicine, Clinical and Experimental Sciences, Human Development in Health Academic Units, University of Southampton, Southampton, UK.7Immune Tolerance Network, Benaroya Research Institute, Seattle, WashingtonCorresponding Authour:Professor George Du ToitPaediatric AllergyBlock B, South WingSt Thomas’ HospitalLondonSE1 7EHTel: 0207 188 9784Email: [email protected] Count: 602Tables: 0Figures: 1Oral Tolerance Induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.(1) OTI to peanut is effective in a general population, with the greatest effect, 81% RRR, noted in the high-risk population.(2) OTI also reduced egg allergy in the general population.(1) Many governmental and allergy societies now recommend introducing peanut in infancy and some suggest other foods, such as well-cooked egg, are also introduced. Choosing which infants should undergo OTI, at what age, to which foods, and under which circumstances is critical for successful OTI prevention in populations where food allergy is a public health concern.Infants with eczema are at increased risk of food allergy but infants from the general population are also at risk and contribute most cases at a population level. Risk of food sensitisation or food allergy increase with age; OTI is most likely to be successful when started in early infancy. Oral tolerance induction from 4 months of age, when completed using standard foods, is safe for nutrition, growth and general child health outcomes (3). Commencing multiple food OTI at 4 months of age, has no detrimental effect on established breastfeeding.(4) All children should adopt a diverse weaning diet, including allergenic foods such as well-cooked egg and peanut, as soon as weaning commences. High risk children should not delay weaning but start weaning and actively include peanut and well-cooked egg, as soon as developmentally ready; usually at about 4 months of age (Fig 1).A 2g/week dosing regime of peanut and well-cooked egg in early infancy is more effective in inducing oral tolerance than later introduction.(5) A lower dosing regime has not been shown to be effective in preventing allergy but, importantly, does not increase allergy risk above that of children who introduce allergenic foods in later infancy.(4) There are limited data regarding the efficacy of OTI to other allergenic foods, or the dose required.(1) All infants should aim to consume about 2g of peanut protein and well-cooked egg per week; parents of high-risk infants should give these amounts more diligently. Given the benefit observed for peanut and egg, it is reasonable for all weaning infants to additionally incorporate 2g of other common and nutritious food allergens; cow’s milk (e.g. as yoghurt), wheat, fish and sesame.Whether children should undergo allergy testing and/or have their first feed of peanut under medical supervision is contested. This cautious approach, potentially requiring large numbers of children to access specialist allergy care, must be balanced against the risks of severe allergic reaction, particularly as most allergic reactions occur on first oral exposure. RCTs of OTI using whole foods had no cases of anaphylaxis on first exposure (4, 6) although anaphylaxis has occurred to OTI using pasteurised whole egg powder.(7) Children with no personal food allergy risk factors do not require testing prior to, or medical supervision during, their first consumption of peanut or well-cooked egg. Children with moderate to severe eczema, or with an existing food allergy should undergo allergy testing +/- OFC at a specialist allergy centre(8), if doing so would not cause undue delay to OTI. It is likely that rapid access to allergy services will be further compromised as a consequence of the COVID-19 pandemic. It may however be that access to SpIgE is available through GP or paediatrician which, if ≥0.35KiU/L, will require referral for OFC. If negative (<0.35KiU/L) the food may be introduced at home following precautionary measures for the first feed: child is well; parent is aware of the signs of IgE mediated reaction has, access to medical support if required and age-appropriate form of the food is given incrementally (Figure 1).

Background This systematic review used the GRADE approach to compile evidence to inform an anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology (EAACI). Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18,449 participants: 29 randomised controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarised narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. Adrenaline is the cornerstone of first-line emergency management of anaphylaxis but, due to ethical constraints, little robust research has assessed its effectiveness . Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. Adrenaline prophylaxis prior to snake bite anti-venom may reduce anaphylaxis but the impact of prophylactic corticosteroids and antihistamines is uncertain. There was insufficient evidence about the impact of other anaphylaxis management strategies. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.

Adolescent and young adult (AYA) patients need additional support while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self-manage their allergies and/or asthma. Transitional care is a complex process which should address the psychological, medical, educational and vocational needs of AYA in the developmentally appropriate way. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of AYA with allergy and/or asthma. This guideline was developed by a multi-disciplinary working panel of experts and patient representatives based on two recent systematic reviews. It sets out a series of general recommendations on operating a clinical service for AYA, which include: (i) starting transition early (11-13 years), (ii) using a structured, multidisciplinary approach, (iii) ensuring AYA fully understand their condition and have resources they can access, (iv) active monitoring of adherence and (v) discussing any implications for further education and work. Specific allergy and asthma transition recommendations include (i) simplifying medication regimes and using reminders; (ii) focusing on areas where AYA are not confident and involving peers in training AYA patients; (iii) identifying and managing psychological and socioeconomic issues impacting disease control and quality of life; (iv) enrolling the family in assisting AYA to undertake self-management and (v) encouraging AYA to let their friends know about their allergies and asthma. These recommendations may need to be adapted to fit into national healthcare systems.