Exhaled Volatile Organic Compounds for Asthma Control Classification in Children with Moderate to Severe Asthma: Results from the SysPharmPediA Study.

RATIONALE: Early identification of children with poorly controlled asthma is imperative for optimizing treatment strategies. The analysis of exhaled volatile organic compounds (VOCs) is an emerging approach to identify prognostic and diagnostic biomarkers in pediatric asthma. OBJECTIVES: To assess the accuracy of gas chromatography-mass spectrometry based exhaled metabolite analysis to differentiate between controlled and uncontrolled pediatric asthma. METHODS: This study encompassed a discovery (SysPharmPediA) and validation phase (U-BIOPRED, PANDA). Firstly, exhaled VOCs that discriminated asthma control levels were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled, based on asthma control test scores and number of severe attacks in the past year. Additionally, potential of VOCs in predicting two or more future severe asthma attacks in SysPharmPediA was evaluated. MEASUREMENTS AND MAIN RESULTS: Complete data were available for 196 children (SysPharmPediA=100, U-BIOPRED=49, PANDA=47). In SysPharmPediA, after randomly splitting the population into training (n=51) and test sets (n=49), three compounds (acetophenone, ethylbenzene, and styrene) distinguished between uncontrolled and controlled asthmatics. The area under the receiver operating characteristic curve (AUROCC) for training and test sets were respectively: 0.83 (95% CI: 0.65-1.00) and 0.77 (95% CI: 0.58-0.96). Combinations of these VOCs resulted in AUROCCs of 0.74 ±0.06 (UBIOPRED) and 0.68 ±0.05 (PANDA). Attacks prediction tests, resulted in AUROCCs of 0.71 (95% CI 0.51-0.91) and 0.71 (95% CI 0.52-0.90) for training and test sets. CONCLUSIONS: Exhaled metabolites analysis might enable asthma control classification in children. This should stimulate further development of exhaled metabolites-based point-of-care tests in asthma.

Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk.

RATIONALE: Lung function in early adulthood is associated with subsequent adverse health outcomes. OBJECTIVES: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function. METHODS: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts. RESULTS: We identified four FEV1/FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p<0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models. CONCLUSIONS: Childhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.

Prevalence of tree nut allergy in Europe: A systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions.

Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy.

The European Academy of Allergy and Clinical Immunology (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. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 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 combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. 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 (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, 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.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk.

Rationale: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. Objectives: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. Methods: Oropharyngeal swabs from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) pediatric asthma or wheezing cohort were characterized using 16S ribosomal RNA gene sequencing, and unsupervised hierarchical clustering was performed on the Bray-Curtis ß-diversity. Enrichment scores of the Molecular Signatures Database hallmark gene sets were computed from the blood transcriptome using gene set variation analysis. Children with severe asthma or severe wheezing were followed up for 12-18 months, with assessment of the frequency of exacerbations. Measurements and Main Results: Oropharyngeal samples from 241 children (age range, 1-17 years; 40% female) revealed four taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia, and Haemophilus. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1% predicted after salbutamol, and annual asthma exacerbation frequency during follow-up. The Veillonella cluster was the most allergic and included the highest percentage of children with two or more exacerbations per year during follow-up. The oropharyngeal clusters were different in the enrichment scores of TGF-ß (transforming growth factor-ß) (highest in the Veillonella cluster) and Wnt/ß-catenin signaling (highest in the Haemophilus cluster) transcriptomic pathways in blood (all q values <0.05). Conclusions: Analysis of the oropharyngeal microbiota of children with asthma or wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with risk for exacerbation and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiologic insights and potentially new treatment approaches.

SQ sublingual immunotherapy tablets for children with allergic rhinitis: A review of phase three trials.

AIM: To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebo-controlled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. METHODS: PubMed searches were conducted and unpublished data were included if necessary. RESULTS: Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials. CONCLUSION: Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease-modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course.

Defining the window of opportunity and target populations to prevent peanut allergy.

BACKGROUND: Peanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants. OBJECTIVE: We aimed to determine the optimal target populations and timing of introduction of peanut products to prevent peanut allergy in the general population. METHODS: Data from the Enquiring About Tolerance (EAT; n = 1303; normal risk; 3-year follow-up; ISRCTN14254740) and Learning Early About Peanut Allergy study (LEAP; n = 640; high risk; 5-year follow-up; NCT00329784) randomized controlled trials plus the Peanut Allergy Sensitization (PAS; n = 194; low and very high risk; 5-year follow-up) observational study were used to model the intervention in a general population. Peanut allergy was defined by blinded peanut challenge or diagnostic skin prick test result. RESULTS: Targeting only the highest-risk infants with severe eczema reduced the population disease burden by only 4.6%. Greatest reductions in peanut allergy were seen when the intervention was targeted only to the larger but lower-risk groups. A 77% reduction in peanut allergy was estimated when peanut was introduced to the diet of all infants, at 4 months with eczema, and at 6 months without eczema. The estimated reduction in peanut allergy diminished with every month of delayed introduction. If introduction was delayed to 12 months, peanut allergy was only reduced by 33%. CONCLUSIONS: The preventive benefit of early introduction of peanut products into the diet decreases as age at introduction increases. In countries where peanut allergy is a public health concern, health care professionals should help parents introduce peanut products into their infants' diet at 4 to 6 months of life.

Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers.

BACKGROUND: Asthma-associated single nucleotide polymorphisms from large genome-wide association studies only explain a fraction of genetic heritability. Likely causes of the missing heritability include broad phenotype definitions and gene-environment interactions (GxE). The mechanisms underlying GxE in asthma are poorly understood. Previous GxE studies on pet ownership showed discordant results. OBJECTIVES: We sought to study the GxE between the 17q12-21 locus and pet ownership in infancy in relation to wheeze. METHODS: Wheezing classes derived from 5 UK-based birth cohorts (latent class analysis) were used to study GxE between the 17q12-21 asthma-risk variant rs2305480 and dog and cat ownership in infancy, using multinomial logistic regression. A total of 9149 children had both pet ownership and genotype data available. Summary statistics from individual analyses were meta-analyzed. RESULTS: rs2305480 G allele was associated with increased risk of persistent wheeze (additive model odds ratio, 1.37; 95% CI, 1.25-1.51). There was no evidence of an association between dog or cat ownership and wheeze. We found significant evidence of a GxE interaction between rs2305480 and dog ownership (P = 8.3 × 10-4) on persistent wheeze; among dog owners, the G allele was no longer associated with an increased risk of persistent wheeze (additive model odds ratio, 0.95; 95% CI, 0.73-1.24). For those without pets, G allele was associated with increased risk of persistent wheeze (odds ratio, 1.61; 95% CI, 1.40-1.86). Among cat owners, no such dampening of the genetic effect was observed. CONCLUSIONS: Among dog owners, rs2305480 G was no longer associated with an increased risk of persistent wheeze (or asthma). Early-life environmental exposures may therefore attenuate likelihood of asthma in those carrying 17q12-21 risk alleles.

Dental age estimation: development and testing of a reference data set for Qatari children, adolescents, and young adults aged between 5 and 25 years.

The purpose of this study is to establish and test a reference data set of dental development of Qatari subjects aged between 5 and 25 years. Radiographs of individuals aged between 5 and 25 years were re-used to establish a reference data set (RDS). A scheme comprising 8 tooth development stages (TDS) was used to assess all the teeth on the left side of the maxilla and mandible. The accuracy of dental age estimation (DAE) was tested with a separate sample of radiographs - the validation sample (VS) comprised 50 females and 50 males of known chronological age (CA). Dental panoramic tomographs (DPT) of 1,597 Qataris were assessed. The summary data for the individual TDS comprising the number (n-tds), mean ( x ¯ -tds), standard deviation (sd-tds), 0th%-ile (the minimum), 25th%-ile, 50th%-ile (the median), 75th%-ile, and 100th%-ile (the maximum) were used to estimate the age of the VS subjects using the simple average method (SAM). There is a significant difference in dental age of 4.8 months in the female group when compared to the CA. The difference in the male group is 4.5 months. This shows similar differences to assessments of other ancestral or ethnic groups.

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study.

BACKGROUND: Asthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds). METHODS: The Clinical Practice Research Datalink Aurum database (2008‒2018) was used to assess annual asthma incidence and prevalence in 1‒17-year-olds and preschool wheeze in 1‒5-year-olds, stratified by sex and age. During the same period, annual asthma exacerbation rates were assessed in those with either a diagnosis of preschool wheeze or asthma. RESULTS: Annual asthma incidence rates decreased by 51% from 1403.4 (95% CI 1383.7 to 1423.2) in 2008 to 688.0 (95% CI 676.3 to 699.9) per 105 person-years (PYs) in 2018, with the most pronounced decrease observed in 1‒5-year olds (decreasing by 65%, from 2556.9 (95% CI 2509.8 to 2604.7) to 892.3 (95% CI 866.9 to 918.3) per 105 PYs). The corresponding decreases for the 6‒11- and 12‒17-year-olds were 36% (1139.9 (95% CI 1110.6 to 1169.7) to 739.9 (95% CI 720.5 to 759.8)) and 20% (572.3 (95% CI 550.4 to 594.9) to 459.5 (95% CI 442.9 to 476.4)) per 105 PYs, respectively. The incidence of preschool wheeze decreased over time and was slightly more pronounced in the 1‒3 year-olds than in the 4-year-olds. Prevalence of asthma and preschool wheeze also decreased over time, from 18.0% overall in 2008 to 10.2% in 2018 for asthma. Exacerbation rates increased over time from 1.33 (95% CI 1.31 to 1.35) per 10 PYs in 2008 to 1.81 (95% CI 1.78 to 1.83) per 10 PYs in 2018. CONCLUSION: Paediatric asthma incidence decreased in the UK since 2008, particularly in 1-5-year-olds; this was accompanied by a decline in asthma prevalence. Preschool wheeze incidence also decreased in this age group. However, exacerbation rates have been increasing.

Narrative review to capture patients' perceptions and opinions about non-response and response to biological therapy for severe asthma.

BACKGROUND: There are now many biological therapies to treat severe asthma. To assess which work best for which patient, we need to develop definitions of response. This narrative review aims to capture severe asthma patients' perceptions about non-response and response to biological therapy. METHODS: Four bibliographic databases were searched from inception to September 2021. Grey literature was searched with the involvement of patient representatives. A thematic approach was used for synthesis. No qualitative studies specifically explore patients' perspectives on response to biological therapy for severe asthma. Three papers and one published asthma patient interview were included. Relevant grey literature was included from online discussion forums, blogs and social media websites. RESULTS: Adult patients framed positive response to biological therapy in terms of reduced burden of disease and treatment. Both were multifaceted. Some patients experienced reduced benefit from biological therapy over time. There was a group of patients who described a limited response or non-response to biological therapy. This was framed within the context of continuing hospitalisation and oral corticosteroid treatment. The speed of onset of benefit was felt to be important by some. CONCLUSIONS: Definitions of non-response and response need to be patient-centred, yet there is a complete lack of qualitative research focused on this topic. By combining relevant published and grey literature we have provided a description of adult patients' perceptions of response to biological therapy in severe asthma. We now need to understand the views of children and adolescents with severe asthma and their carers, and diverse patient experiences in real-world settings.

Identifying and appraising outcome measures for severe asthma: a systematic review.

BACKGROUND: Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing end-points for severe asthma is unclear. This review aimed to identify outcome measures for severe asthma and appraise the quality of their measurement properties. METHODS: A literature search was performed to identify "candidate" outcome measures published between 2018 and 2020. A modified Delphi exercise was conducted to select "key" outcome measures within healthcare professional, patient, pharmaceutical and regulatory stakeholder groups. Initial validation studies for "key" measures were rated against modified quality criteria from COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The evidence was discussed at multi-stakeholder meetings to ratify "priority" outcome measures. Subsequently, four bibliographic databases were searched from inception to 20 July 2020 to identify development and validation studies for these end-points. Two reviewers screened records, extracted data, assessed their methodological quality and graded the evidence according to COSMIN. RESULTS: 96 outcome measures were identified as "candidates", 55 as "key" and 24 as "priority" for severe asthma, including clinical, healthcare utilisation, quality of life, asthma control and composite. 32 studies reported measurement properties of 17 "priority" end-points from the latter three domains. Only the Severe Asthma Questionnaire and Childhood Asthma Control Test were developed with input from severe asthma patients. The certainty of evidence was "low" to "very low" for most "priority" end-points across all measurement properties and none fulfilled all quality standards. CONCLUSIONS: Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.

Prediction of adult asthma risk in early childhood using novel adult asthma predictive risk scores.

BACKGROUND: Numerous risk scores have been developed to predict childhood asthma. However, they may not predict asthma beyond childhood. We aim to create childhood risk scores that predict development and persistence of asthma up to young adult life. METHODS: The Isle of Wight Birth Cohort (n = 1456) was prospectively assessed up to 26 years of age. Asthma predictive scores were developed based on factors during the first 4 years, using logistic regression and tested for sensitivity, specificity and area under the curve (AUC) for prediction of asthma at (i) 18 and (ii) 26 years, and persistent asthma (PA) (iii) at 10 and 18 years, and (iv) at 10, 18 and 26 years. Models were internally and externally validated. RESULTS: Four models were generated for prediction of each asthma outcome. ASthma PredIctive Risk scorE (ASPIRE)-1: a 2-factor model (recurrent wheeze [RW] and positive skin prick test [+SPT] at 4 years) for asthma at 18 years (sensitivity: 0.49, specificity: 0.80, AUC: 0.65). ASPIRE-2: a 3-factor model (RW, +SPT and maternal rhinitis) for asthma at 26 years (sensitivity: 0.60, specificity: 0.79, AUC: 0.73). ASPIRE-3: a 3-factor model (RW, +SPT and eczema at 4 years) for PA-18 (sensitivity: 0.63, specificity: 0.87, AUC: 0.77). ASPIRE-4: a 3-factor model (RW, +SPT at 4 years and recurrent chest infection at 2 years) for PA-26 (sensitivity: 0.68, specificity: 0.87, AUC: 0.80). ASPIRE-1 and ASPIRE-3 scores were replicated externally. Further assessments indicated that ASPIRE-1 can be used in place of ASPIRE-2-4 with same predictive accuracy. CONCLUSION: ASPIRE predicts persistent asthma up to young adult life.

Early introduction of peanut reduces peanut allergy across risk groups in pooled and causal inference analyses.

BACKGROUND: The Learning Early About Peanut allergy (LEAP) study has shown the effectiveness of early peanut introduction in prevention of peanut allergy (PA). In the Enquiring About Tolerance (EAT) study, a statistically significant reduction in PA was present only in per-protocol (PP) analyses, which can be subject to bias. OBJECTIVE: The aim of this study was to combine individual-level data from the LEAP and EAT trials and provide robust evidence on the bias-corrected, causal effect of early peanut introduction. METHOD: As part of the European Union-funded iFAAM project, this pooled analysis of individual pediatric patient data combines and compares effectiveness and efficacy estimates of oral tolerance induction among different risk strata and analysis methods. RESULTS: An intention-to-treat (ITT) analysis of pooled data showed a 75% reduction in PA (p < .0001) among children randomized to consume peanut from early infancy. A protective effect was present across all eczema severity groups, irrespective of enrollment sensitization to peanut, and across different ethnicities. Earlier age of introduction was associated with improved effectiveness of the intervention. In the pooled PP analysis, peanut consumption reduced the risk of PA by 98% (p < .0001). A causal inference analysis confirmed the strong PP effect (89% average treatment effect relative risk reduction p < .0001). A multivariable causal inference analysis approach estimated a large (100%) reduction in PA in children without eczema (p = .004). CONCLUSION: We demonstrate a significant reduction in PA with early peanut introduction in a large group of pooled, randomized participants. This significant reduction was demonstrated across all risk subgroups, including children with no eczema. Furthermore, our results point to increased efficacy of the intervention with earlier age of introduction.

A practical toolbox for the effective transition of adolescents and young adults with asthma and allergies: An EAACI position paper.

INTRODUCTION: 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. AIM: We herein summarize practical resources to support this guideline's implementation in clinical practice. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Frequency of food allergy in Europe: An updated systematic review and meta-analysis.

Food allergy (FA) is increasingly reported in Europe, however, the latest prevalence estimates were based on studies published a decade ago. The present work provides the most updated estimates of the prevalence and trends of FA in Europe. Databases were searched for studies published between 2012 and 2021, added to studies published up to 2012. In total, 110 studies were included in this update. Most studies were graded as moderate risk of bias. Pooled lifetime and point prevalence of self-reported FA were 19.9% (95% CI 16.6-23.3) and 13.1% (95% CI 11.3-14.8), respectively. The point prevalence of sensitization based on specific IgE (slgE) was 16.6% (95% CI 12.3-20.8), skin prick test (SPT) 5.7% (95% CI 3.9-7.4), and positive food challenge 0.8% (95% CI 0.5-0.9). While lifetime prevalence of self-reported FA and food challenge positivity only slightly changed, the point prevalence of self-reported FA, sIgE and SPT positivity increased from previous estimates. This may reflect a real increase, increased awareness, increased number of foods assessed, or increased number of studies from countries with less data in the first review. Future studies require rigorous designs and implementation of standardized methodology in diagnosing FA, including use of double-blinded placebo-controlled food challenge to minimize potential biases.

Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper.

INTRODUCTION: In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. METHODS: The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. RESULTS: Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. CONCLUSION: This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT.

Prevalence estimates of eight big food allergies in Europe: Updated systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology published prevalence estimates for food allergy (FA) and food sensitization (FS) to the so-called eight big food allergens (i.e. cow's milk, egg, wheat, soy, peanut, tree nuts, fish and shellfish) in Europe for studies published between 2000 and 2012. The current work provides 10-year updated prevalence estimates for these food allergens. A protocol was registered on PROSPERO before starting the research (reference number CRD42021266657). Six databases were searched for studies published 2012-2021, added to studies published up to 2012, resulting in a total of 93 studies. Most studies were graded as at moderate risk of bias. The overall pooled estimates for all age groups of self-reported lifetime prevalence were as follows: cow's milk (5.7%, 95% confidence interval 4.4-6.9), egg (2.4%, 1.8-3.0), wheat (1.6%, 0.9-2.3), soy (0.5%, 0.3-0.7), peanut (1.5%, 1.0-2.1), tree nuts (0.9%, 0.6-1.2), fish (1.4%, 0.8-2.0) and shellfish (0.4%, 0.3-0.6). The point prevalence of food challenge-verified allergy were as follows: cow's milk (0.3%, 0.1-0.5), egg (0.8%, 0.5-1.2), wheat (0.1%, 0.01-0.2), soy (0.3%, 0.1-0.4), peanut (0.1%, 0.0-0.2), tree nuts (0.04%, 0.02-0.1), fish (0.02%, 0.0-0.1) and shellfish (0.1%, 0.0-0.2). With some exceptions, the prevalence of allergy to common foods did not substantially change during the last decade; variations by European regions were observed.

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.