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BackgroundEffectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

Anaphylaxis is a medical emergency with adrenaline acknowledged as the first line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10 minutes to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants, and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes.

Background: Childhood food allergy (FA) and food allergen sensitization (FAS) are associated with allergic airway disease(s) [AAD] (asthma and rhinitis) in childhood. However, the associations between childhood FA/FAS and AAD in adulthood are not well described. Methods: We investigated the longitudinal relationship between childhood FA/FAS to common food allergens and AAD at 18 and 26 years, in the Isle of Wight birth cohort. Study subjects (N = 1456) were followed up at fixed time points from ages 1–26 years for FA/FAS status. AAD were evaluated from 4 years onwards. The associations between FA/FAS and AAD were assessed with univariate analyses and then multivariable logistic regression, adjusting for clinically relevant co-variates. Results: Food allergy at 4 years was significantly associated with asthma at 18 years [adjusted odds ratio (aOR): 2.75, 95% CI: 1.53–4.92, p =.001] and 26 years (aOR: 2.62, 95% CI: 1.32–5.20, p =.006). Conversely, childhood FA was not associated with adulthood rhinitis whatsoever. While FAS at ages 4 and 10 were associated with both AAD, the associations between FAS and rhinitis were less robust relative to asthma. Conclusion: Childhood FA increased the odds of asthma during adulthood by nearly threefold. Additionally, childhood FAS was also associated with increased odds of asthma in adulthood. Conversely, FAS but not FA in childhood was associated with rhinitis in adulthood. We suggest that children with FA/FAS should be followed up to facilitate early detection and intervention of subsequent AAD, particularly asthma.

Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity? Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry. Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV 1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels. Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

Background: There are limited data describing lung function changes in children after an asthma exacerbation. Our hypothesis was that lung function does not fully recover in children in the months following an asthma exacerbation. Methods: We used a data set of children with asthma where lung function (including FEV1, FEV1/FVC ratio and FEF25-75) was measured at 3-month intervals over a year. Mixed-level models compared spirometry measured on two occasions 3 months apart before a single exacerbation (assessments 1 and 2) with measurements made on two occasions after the exacerbation (assessments 3 and 4), with adjustment for covariates. Changes in spirometry over a year were also analysed across those with exacerbations in no, one or more than one 3-month periods. Results: For the 113 children who had a single exacerbation, spirometry measured at assessments 1 or 2 did not differ from measurements at assessments 3 or 4 when the whole population was considered. When stratified into tertiles by change in %FEV1 between assessments 2 and 3, those with the greater reduction were more likely to be treated with long-acting beta-agonist, but in this category, %FEV1 at assessment 4 had returned to the value at assessment 1. %FEV1 did not change over a 12-month period within and between the three exacerbation categories (n = 809). Conclusion: One or more asthma exacerbation was not associated with a fall in lung function for the whole population. In a subset of individuals, lung function does fall after an exacerbation but returns to pre-exacerbation values after a period of months.

In the second of two linked articles, we describe the development in clinical as described by Clinical & Experimental Allergy and other journals in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered. In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered.

In the first of two linked articles, we describe the development in the mechanisms underlying allergy as described by Clinical & Experimental Allergy and other journals in 2019. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered.

BACKGROUND: Electronic noses (eNoses) are emerging point-of-care tools that may help in the subphenotyping of chronic respiratory diseases such as asthma.OBJECTIVE: We aimed to investigate whether eNoses can classify atopy in pediatric and adult patients with asthma.METHODS: Participants with asthma and/or wheezing from 4 independent cohorts were included; BreathCloud participants (n = 429), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adults (n = 96), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes pediatric participants (n = 100), and Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory Effects 2 participants (n = 30). Atopy was defined as a positive skin prick test result (≥3 mm) and/or a positive specific IgE level (≥0.35 kU/L) for common allergens. Exhaled breath profiles were measured by using either an integrated eNose platform or the SpiroNose. Data were divided into 2 training and 2 validation sets according to the technology used. Supervised data analysis involved the use of 3 different machine learning algorithms to classify patients with atopic versus nonatopic asthma with reporting of areas under the receiver operating characteristic curves as a measure of model performance. In addition, an unsupervised approach was performed by using a bayesian network to reveal data-driven relationships between eNose volatile organic compound profiles and asthma characteristics.RESULTS: Breath profiles of 655 participants (n = 601 adults and school-aged children with asthma and 54 preschool children with wheezing [68.2% of whom were atopic]) were included in this study. Machine learning models utilizing volatile organic compound profiles discriminated between atopic and nonatopic participants with areas under the receiver operating characteristic curves of at least 0.84 and 0.72 in the training and validation sets, respectively. The unsupervised approach revealed that breath profiles classifying atopy are not confounded by other patient characteristics.CONCLUSION: eNoses accurately detect atopy in individuals with asthma and wheezing in cohorts with different age groups and could be used in asthma phenotyping.

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.

Один из парадоксов мейнстримного советского кино заключался в том, что оно имело склонность «создавать зрелище «маскулинной телесности, не привлекая (по большей части) внимания к ней в откровенном смысле. Тело героя было мифологизировано в патриархальных структурах, что воспринималось, как естественное положение вещей. В данной работе рассматриваются различные пути, с помощью которых режиссер Кира Муратова бросает вызов этой культурной парадигме, выдвигая на первый план более откровенное мужское тело, тем самым разрушая мужской взгляд на вещи. В этом отношении фильмы Киры Муратовой бросают вызов архетипичным образам маскулинности (и фемининности), распространенным не только в Советском Союзе или в мейнстримном кино, но и во многих других странах.

Background: the heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. Methods: following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87–0.92, specificity 0.73–0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10 −6–1.23 × 10 −3). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Rationale: Mast cells (MCs) play a role in inflammation and both innate and adaptive immunity, but their involvement in severe asthma (SA) remains undefined. Objectives: We investigated the phenotypic characteristics of the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) asthma cohort by applying published MC activation signatures to the sputum cell transcriptome. Methods: Eighty-four participants with SA, 20 with mild/moderate asthma (MMA), and 16 healthy participants without asthma were studied. We calculated enrichment scores (ESs) for nine MC activation signatures by asthma severity, sputum granulocyte status, and three previously defined sputum molecular phenotypes or transcriptome-associated clusters (TACs) 1, 2, and 3 using gene set variation analysis. Measurements and Main Results: MC signatures except unstimulated, repeated FceR1-stimulated and IFN-g–stimulated signatures were enriched in SA. A FceR1-IgE–stimulated and a single-cell signature from asthmatic bronchial biopsies were highly enriched in eosinophilic asthma and in the TAC1 molecular phenotype. Subjects with a high ES for these signatures had elevated sputum amounts of similar genes and pathways. IL-33– and LPS-stimulated MC signatures had greater ES in neutrophilic and mixed granulocytic asthma and in the TAC2 molecular phenotype. These subjects exhibited neutrophil, NF-kB (nuclear factor-kB), and IL-1b/TNF-a (tumor necrosis factor-a) pathway activation. The IFN-g–stimulated signature had the greatest ES in TAC2 and TAC3 that was associated with responses to viral infection. Similar results were obtained in an independent ADEPT (Airway Disease Endotyping for Personalized Therapeutics) asthma cohort. Conclusions: Gene signatures of MC activation allow the detection of SA phenotypes and indicate that MCs can be induced to take on distinct transcriptional phenotypes associated with specific clinical phenotypes. IL-33–stimulated MC signature was associated with severe neutrophilic asthma, whereas IgE-activated MC was associated with an eosinophilic phenotype.

BACKGROUND: More than 17 million people across Europe have allergies to food and the burden of food allergies is increasing. In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published guidelines for preventing food allergy. Important research has been published since then and it is essential to ensure the guidelines reflect the latest evidence. A systematic review will be undertaken to help prepare new guidelines due to be published in 2020.METHODS: Eleven bibliographic databases will be searched from inception to 31 October 2019 for randomized controlled trials about any intervention designed to prevent the development of new cases of immediate-type/IgE-mediated food allergy in infants, children and adults. There are few randomized controlled trials about the impact of breastfeeding on food allergy so prospective cohort studies about breastfeeding with at least 1000 participants at general risk or 200 at high risk of food allergy will also be eligible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty of the evidence and tabulate summary data. The risk of bias in individual trials will be assessed using the Cochrane risk of bias tool. All data extraction and quality appraisal will be undertaken independently by two reviewers in partnership with a taskforce of EAACI members.CONCLUSIONS: Preventing food allergy has the potential to improve personal well-being and reduce societal healthcare costs. It is important that forthcoming European guidelines take the latest research into account. Past reviews have tended to focus on single interventions or combined food allergy with other outcomes, making it difficult to draw robust conclusions about potential impacts for policy and practice.

Background Dental age estimation can assist in the identification of victims following natural disasters and it can also help to solve birth date disputes in individuals involved in criminal activities. A reference dataset (RDS) has been developed from the dental development of 2306 subjects of southern Han Chinese origin and subsequently validated. This study aimed to test the applicability of the southern Han Chinese dental maturation RDS on three distinct East Asian population groups. Methods A total of 953 dental panoramic radiographs of subjects aged 2 to 24 years were obtained from Philippines, Thailand and Japan. The staging of dental development was conducted according to Anglo-Canadian classification system. The dental age (DA) was calculated using six methods; one un-weighted average and five weighted average (n-tds, sd-tds, se-tds, 1/sd-tds, 1/se-tds) methods based on the scores of the southern Han Chinese RDS. Statistical significance was set at p Results From six dental age calculations, all methods of DA accurately estimated the age of Japanese and few methods in Filipino subjects (n-tds, 1/sd-tds, 1/se-tds). There was consistent overestimation of age for all the methods for Thai females (p Conclusions The southern Han Chinese dental reference dataset was shown to be most accurate for Japanese, followed by Thai males and it was particularly ineffective for Filipinos and Thai females.

Funder: NIHR Cambridge Biomedical Research Centre, Population differences in dental development between Black and White ethnic groups have been debated but not previously studied in the UK. Using inappropriate data for dental age estimation (DAE) could lead to erroneous results and injustice. Data were collected from dental panoramic radiographs of 5590 subjects aged 6-24 years in a teaching hospital archive. Demirjian stages were determined for left-sided teeth and third molars and data collected regarding hypodontia and third molar agenesis. Third molar development in self-assigned Black British, including other self-assigned Black ethnicity, was compared with that of self-assigned White British subjects. Data were compared for males and females in the two ethnic groups using T-tests for Demirjian Stages A-G of third molar development and Mann-Whitney tests for Stage H once a cut-off age at the maximum age for Stage G had been imposed. Third molar development occurred earlier in subjects of Black ancestry compared to those of White ancestry. While both ethnic groups showed large age ranges for every third molar stage, in female subjects these generally occurred at least 1.5 years earlier, and in males at least one year earlier. Hypodontia and third molar agenesis were more prevalent in White British, but the ethnic difference in third molar development persisted in subjects with complete dentitions. This is a large study that confirms ethnic differences in a London population, emphasises the difficulties of establishing the 18-year-old threshold using DAE, and confirms the risk of overestimating the age of individuals of Black ethnicity using White ethnic reference data.

Accurate regulation of cutaneous immunity is fundamental for human health and quality of life but is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance vs inflammation in human skin, we set up a human in vivo allergen challenge study, exposing patients with atopic dermatitis (AD) to house dust mite (HDM). Analyses of transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of resident and infiltrating immune cells indicated that inflammatory responses to HDM were associated with immune activation in Langerhans cells (LCs) and cutaneous T cells. High basal level of TNFα production by cutaneous Th17 T cells predisposed to an inflammatory reaction and resulted in formation of hub structures where LCs and T cells interacted, leading to loss of functional programming in LCs. Additionally, single nucleotide polymorphisms in MT1X gene associated with enhanced expression of metallothioneins and transcriptional programmes encoding antioxidant defences across skin cell types in non-reactive patients, were protective against T cell mediated inflammation. Our results provide a unique insight into the dynamics of immune regulation in the human skin and define regulatory circuits that can be harnessed to improve skin health and treat disease.

Introduction\ud \ud Food hypersensitivity (FHS), including food allergy, coeliac disease and food intolerance, is a major public health issue. The Food Standards Agency (FSA), an independent UK Government department working to protect public health and consumers’ wider interests in food, sought to identify research priorities in the area of FHS.\ud \ud \ud \ud Methods\ud \ud A priority setting exercise was undertaken, using a methodology adapted from the James Lind Alliance—the first such exercise with respect to food hypersensitivity. A UK-wide public consultation was held to identify unanswered research questions. After excluding diagnostics, desensitization treatment and other questions which were out of scope for FSA or where FSA was already commissioning research, 15 indicative questions were identified and prioritized by a range of stakeholders, representing food businesses, patient groups, health care and academia, local authorities and the FSA.\ud \ud \ud \ud Results\ud \ud 295 responses were received during the public consultation, which were categorized into 70 sub-questions and used to define 15 key evidence uncertainties (‘indicative questions’) for prioritization. Using the JLA prioritization framework, this resulted in 10 priority uncertainties in evidence, from which 16 research questions were developed. These could be summarized under the following 5 themes: communication of allergens both within the food supply chain and then to the end consumer (ensuring trust in allergen communication); the impact of socio-economic factors on consumers with FHS; drivers of severe reactions; mechanism(s) underlying loss of tolerance in FHS; and the risks posed by novel allergens/processing.\ud \ud \ud \ud Discussion\ud \ud In this first research prioritization exercise for food allergy and FHS, key priorities identified to protect the food-allergic public were strategies to help allergic consumers to make confident food choices, prevention of FHS and increasing understanding of socio-economic impacts. Diagnosis and treatment of FHS was not considered in this prioritization.

The global prevalence of severe asthma among adolescents ranges from 4% to 11%; and up to 7% of children with asthma display an uncontrolled and severe form that is often associated with a substantial burden on the quality of life of patients and their families, and increasing costs of healthcare [1, 2]. “Childhood asthma” is an umbrella term describing a heterogeneous disease comprising different phenotypes and a wide range of symptoms [3–5]., A digital multidisciplinary European expert meeting took place on the 9 July 2020 to identify the unmet needs of paediatric severe asthma patients, and set the priorities for clinical and research activities ahead https://bit.ly/3CeLBHB

The 3TR (Taxonomy, Treatments, Targets and Remission) consortium is the largest IMI (Innovative Medicine Initiative) project ever started in the field of immune diseases (https://3tr-imi.eu/). 3TR is unique in bringing several medical specialties, encompassing respiratory medicine, rheumatology, neurology and gastroenterology, together, to study disease mechanisms across seven disease entities: asthma, COPD, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, ulcerative colitis and Crohn's disease. [...]

Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognise and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritise clinical trials with the potential to improve the management of patients at risk of anaphylaxis. Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognize and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first-line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritize clinical trials with the potential to improve the management of patients at risk of anaphylaxis.

Oral Tolerance Induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.(1, 2) OTI to peanut is highly effective in a high-risk population with an 81% relative risk ration (RRR) to peanut allergy .(3) OTI also reduced egg allergy in the general population in a per protocol analysis.(1) These published RCT findings have changed practice and many governmental and allergy societies now recommend introducing peanut in infancy; some suggest that other foods, such as well-cooked egg, are also introduced. Only National Institute of Allergy and Infectious Diseases (NIAID) stratify their recommendations according to food allergy (FA) risk level.

We are writing in response to the British Society of Allergy and Clinical Immunology (BSACI) egg allergy guideline, published earlier this year in your Journal [1]. The guideline includes a section on the home introduction of egg. This makes the point that home introduction is not the same as a food challenge. It further describes which children can reintroduce egg at home, for example those without asthma or with well controlled asthma and only mild to moderate symptoms on previous exposures.

BACKGROUND: This guideline from the European Academy of Allergy and Clinical Immunology (EAACI) recommends approaches to prevent the development of immediate-onset / IgE-mediated food allergy in infants and young children. It is an update of a 2014 EAACI guideline.METHODS: The guideline was developed using the AGREE II framework and the GRADE approach. An international Task Force with representatives from 11 countries and different disciplinary and clinical backgrounds systematically reviewed research and considered expert opinion. Recommendations were created by weighing up benefits and harms, considering the certainty of evidence and examining values, preferences and resource implications. The guideline was peer-reviewed by external experts and feedback was incorporated from public consultation.RESULTS: All of the recommendations about preventing food allergy relate to infants (up to one year) and young children (up to five years), regardless of risk of allergy. There was insufficient evidence about preventing food allergy in other age groups. The EAACI Task Force suggests avoiding the use of regular cow's milk formula as supplementary feed for breast fed infants in the first week of life. The EAACI Task Force suggests introducing well cooked, but not raw egg or uncooked pasteurised egg, into the infant diet as part of complementary feeding. In populations where there is a high prevalence of peanut allergy, the EAACI Task Force suggests introducing peanuts in an age-appropriate form as part of complementary feeding. According to the studies, it appears that the most effective age to introduce egg and peanut is from four to six months of life. The EAACI Task Force suggests against the following for preventing food allergy: (i) avoiding dietary food allergens during pregnancy or breastfeeding; and (ii) using soy protein formula in the first six months of life as a means of preventing food allergy. There is no recommendation for or against the following: use of vitamin supplements, fish oil, prebiotics, probiotics or synbiotics in pregnancy, when breastfeeding or in infancy; altering the duration of exclusive breastfeeding; hydrolysed infant formulas, regular cow's milk based infant formula after a week of age or use of emollients.CONCLUSIONS: Key changes from the 2014 guideline include suggesting (i) the introduction of peanut and well-cooked egg as part of complementary feeding (moderate certainty of evidence) and (ii) avoiding supplementation with regular cow's milk formula in the first week of life (low certainty of evidence). There remains uncertainty in how to prevent food allergy and further well-powered, multinational research using robust diagnostic criteria is needed.

Background Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan‐European, population‐based birth cohort study have been lacking. This study compares the prevalence and early‐life risk factors of these diseases in European primary school children. Methods In the prospective multicentre observational EuroPrevall‐iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC‐based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these. Results From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family‐allergy‐score, odds ratio (OR) 1.50 (95% CI 1.32–1.70) per standard deviation; early‐life allergy symptoms, OR 2.72 (2.34–3.16) for each symptom; and caesarean birth, OR 1.35 (1.04–1.76). Female gender, OR 0.72 (0.58–0.90); older siblings, OR 0.79 (0.63–0.99); and day care, OR 0.81 (0.63–1.06) were protective factors. Conclusion Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early‐life factors are modifiable and may be considered for prevention strategies., Allergic multimorbidity (coexistence of asthma, eczema and allergic rhinitis) is common among European children at primary school age, with 7% of study participants affected. Protective factors identified in the study include female sex, having older siblings and attending day care. Risk factors include history of allergic diseases in first‐degree family members, early‐age symptoms and caesarean birth.

One hundred and ten years after Noon's first clinical report of the subcutaneous application of allergen extracts, allergen immunotherapy (AIT) has evolved as the most important pillar of the treatment of allergic patients. It is the only disease-modifying treatment option available and the evidence for its clinical efficacy and safety is broad and undisputed. Throughout recent decades, more insights into the underlying mechanisms, in particular the modulation of innate and adaptive immune responses, have been described. AIT is acknowledged by worldwide regulatory authorities, and following the regulatory guidelines for product development, AIT products are subject to a rigorous evaluation before obtaining market authorization. Knowledge and practice are anchored in international guidelines, such as the recently published series of the European Academy of Allergy and Clinical Immunology (EAACI). Innovative approaches continue to be further developed with the focus on clinical improvement by, for example, the usage of adjuvants, peptides, recombinants, modification of allergens, new routes of administration, and the concomitant use of biologicals. In addition, real-life data provide complementary and valuable information on the effectiveness and tolerability of this treatment option in the clinical routine. New mobile health technologies and big-data approaches will improve daily treatment convenience, adherence, and efficacy of AIT. However, the current coronavirus disease 2019 (COVID-19) pandemic has also had some implications for the feasibility and practicability of AIT. Taken together, AIT as the only disease-modifying therapy in allergic diseases has been broadly investigated over the past 110 years laying the path for innovations and further improvement.

The determination of age of majority (the 18-year-old threshold) using the popular Demirjian tooth staging method is unreliable, so other maturity markers are required. This study examines whether the Root Pulp Visibility (RPV) of the mandibular third molar is a useful indicator of age. One thousand six dental panoramic radiographs (DPTs) were examined and the left mandibular third molar assessed according to the RPV stages using the method of Olze et al. (Int J Legal Med 124:183–186, 2010) as modified by Lucas et al. (Forensic Sci Int 270:98–102, 2017). Six hundred sixty-two DPTs, 288 males and 374 females, satisfied the inclusion criteria. Individuals who had reached stages RPV-A and RPV-B were represented in a wide range of ages spanning the 18-year-old threshold. Individuals who had reached stages RPV-C and RPV-D were all above the 18-year-old threshold. It was not possible to analyse a large number of DPTs for various reasons. Individuals whose mandibular third molar exhibited stages RPV-C and RPV-D may be deemed to have reached the age of majority. These results are consistent with other published studies. Variation in the rate of development of the third molar limits the applicability of this method. RPV staging is an accurate method of determining the 18-year-old threshold. Substitute methods are required in a large number of cases.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence- based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients.

Food allergy is a major public health concern with avoidance of the trigger food(s) being central to management by the patient. Food information legislation mandates the declaration of allergenic ingredients; however, the labelling of the unintentional presence of allergens is less defined. Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the risk of reaction from the unintended presence of allergens in foods. In its current form, PAL is counterproductive for consumers with food allergies as there is no standardised approach to applying PAL. Foods with a PAL often do not contain the identified food allergen while some products without a PAL contain quantities of common food allergens that are capable of inducing an allergic reaction. Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) was an EU-funded project that aimed to improve the management of food allergens by the food industry for the benefit of people with food allergies. Within iFAAM, a clinically validated tiered risk assessment approach for food allergens was developed. Two cross-stakeholder iFAAM workshops were held on 13th -14th December 2016 and 19th -20th April 2018. One of the objectives of these workshops was to develop a proposal to make PAL effective for consumers. This paper describes the outcomes from these workshops. This provides the basis for the development of more informative and transparent labelling that will ultimately improve management and well-being in consumers with food allergy. This article is protected by copyright. All rights reserved.

Aim The aim of this study was to analyse the correlation between skeletal and dental maturity. Materials and methods The Dental Panoramic Tomogram and Lateral Skull Radiographs of 381 subjects aged between 8.20 years and 17.96 years were examined. Calcification stages of all the teeth on the left hand side and all third molars were determined according to Demirjians 8-stages, whilst the Cervical Vertebral Maturation (CVM) Index was adopted for the assessment of skeletal maturity. Dental age (DA) was determined using the simple weighted average method. Results There was no significant difference between DA and chronological age (CA) of the male and female groups. The Spearman rank correlation between CA and CVM was moderate, whilst the correlation between DA and CVM was weak. A moderate correlation was found between the dental calcification stages and CVM for the upper right third molar in males. Conclusions The average CA of females at every CVM stage was below that of males, confirming that females undergo earlier skeletal maturation. The similarity between CA and DA confirms that CA can be closely approximated by DA. The low correlations between CA and DA with CVM suggest that these variables should not be used in determining the growth status or potential of the individual.

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; utilizing 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 summarizes 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. © 2019 John Wiley & Sons Ltd.

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence).

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and &lt, 1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), &lt, 1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

One of the most ignored aspects of the COVID-19 pandemic has been the impact of public health measures by governments on wider health and welfare. From March 2020, hospitals in the UK saw a dramatic reduction in patients with cancer presenting due to multifactorial reasons. The impact of the pandemic on patients with cancer in the South East London Cancer Alliance was studied. The specific aims were (1) to examine the reduction in cancer diagnoses during the first wave of the pandemic and (2) to examine the stage of diagnosis of patients with cancer presenting during the pandemic compared with that of patients presenting before the pandemic. There was an 18.2% reduction in new cancer diagnoses (an estimate of 987 cancers), when compared with 2019. This fall in cancer diagnoses was most marked in patients with prostate (51.4%), gynaecological (29.7%), breast (29.5%) and lung (23.4%) cancers. There was an overall 3.9% increase in advanced stage presentation (Stages 3 and 4), with an overall 6.8% increase in Stage 4 cancers during this period. The greatest shifts were seen in lung (increase of 6.3%, with an 11.2% increase in Stage 4 cancer alone) and colorectal (5.4%) cancers. For prostate cancer, there was an increase in 3.8% in those presenting with Stage 4 disease. For breast cancer, there was an 8% reduction in patients diagnosed with Stage 1 cancer with commensurate increases in the proportion of those with Stage 2 disease. The experiences in cancer are a salient warning that pandemic control measures and policy need to balance all health and welfare. Alternative strategies need to be adopted during further waves of the current and any future pandemic to ensure that patients with cancer are prioritised for diagnosis and treatment to prevent late-stage presentation and an increase in avoidable deaths.