BACKGROUND:Allergic rhinitis displays a relevant impact on quality of life. Medications used in the treatment of rhinitis have been assessed on their impact on rhinoconjunctivitis-related quality of life, but not on generic health-related quality of life metrics, such as utilities or EQ-5D visual analogue scale (VAS) levels. This study aimed to compare different medication classes and individual medications on utilities and EQ-5D VAS levels using data from a mobile app. METHODS:We conducted an observational study using direct patient data from the MASK-air mobile application, collected between May 2015 and December 2024. We compared rhinitis medication classes and individual medications on health utilities (computed from the EQ-5D-5L questionnaire) and the EQ-5D VAS. To account for confounding, we employed inverse probability treatment weighting based on propensity scores, adjusting for demographics, baseline symptom control, and asthma status. RESULTS:The study analysed 69,973 observations with EQ-5D VAS data and 842 observations with utility data. At the medication class level, fixed combinations of intranasal antihistamines and corticosteroids were associated with improvements in EQ-5D VAS (mean difference = 1.900; 95% CI = 1.316-2.484) and utilities (mean difference = 0.022; 95% CI = -0.015 to 0.059) compared with oral antihistamines (OAH). Intranasal antihistamines were associated with lower EQ-5D VAS and utility scores than other intranasal treatments. For individual medications, mometasone was associated with a lower EQ-5D VAS than budesonide and fluticasone furoate, while fexofenadine and levocetirizine tended to be associated with lower VAS values than other OAH. CONCLUSION:Fixed combinations of intranasal antihistamines and corticosteroids were associated with better quality-of-life than oral antihistamines and intranasal antihistamines. These findings could support future cost-effectiveness analyses.

BACKGROUND:Children with uncontrolled, moderate-to-severe asthma often have type 2 disease with allergic sensitization and/or elevated serum IgE. OBJECTIVE:To examine dupilumab efficacy in children aged 6 to 11 years with/without allergen sensitization. METHODS:In VOYAGE (NCT02948959), 408 children were randomized to receive dupilumab 100/200 mg every 2 weeks (by weight) or placebo for 52 weeks. This post hoc analysis included 336 children from VOYAGE with type 2 inflammation (eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) and known baseline allergen sensitization status (based on total serum IgE and perennial allergen-specific IgE levels). The primary outcome assessed was annualized severe exacerbation rate; we also assessed change from baseline in pre- and postbronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1), Interviewer-Administered 7-Item Asthma Control Questionnaire (ACQ-7-IA) score, and total and allergen-specific IgE levels. RESULTS:Of 336 children with type 2 inflammation and known baseline allergen sensitization status, 75 (22%) were nonsensitized, 58 (17%) monoallergen sensitized, and 203 (60%) multiallergen sensitized. Dupilumab versus placebo reduced asthma exacerbations by 45%, 75%, and 60% in the non-, mono-, and multisensitized subgroups (P = .1286, .0376, and .0004), respectively, by week 52, with no apparent interaction between treatment group and sensitization status (Pint = .48). Similar improvements were observed across sensitization subgroups for pre- and postbronchodilator ppFEV1, ACQ-7-IA, and total IgE levels. CONCLUSION:In children with type 2 asthma, dupilumab showed significant efficacy, reducing exacerbations and improving other outcomes in monoallergen- and multiallergen-sensitized patients, and numerical but nonsignificant effects in nonsensitized patients.

Allergic Rhinitis and its Impact on Asthma (ARIA) was, up until 2017, a guideline using the best evidence (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) and developed as a change management strategy. A second change management strategy-in collaboration with the European Academy of Allergy and Clinical Immunology (ARIA-EAACI)-was developed as a person-centred, digitally enabled, artificial intelligence-assisted care (person-centred care) with strong political involvement. The digital tools of ARIA are mainly based on MASK-air, an Organisation for Economic Co-operation and Development (OECD) Best Practice for integrated care for chronic diseases. Artificial intelligence was used, in particular, to approach the patients' views and expectations. The current paper describes the steps to build and achieve a new change management strategy. The future of the Change Management strategy is (i) a collaboration between ARIA and EAACI, (ii) the development of ARIA 2024-2025 guidelines, (iii) the new ARIA-MeDALL classification of multimorbid airway diseases and (iv) embedding MASK-air in a registry for severe allergic diseases. The ultimate goals of the ARIA-EAACI change management strategy will be (i) the transformation of health and care in rhinitis and asthma multimorbidity and (ii) the development of novel guidelines and policies in a cost-effective manner, improving shared-decision-making.

BACKGROUND:Respiratory viruses, frequently detected in asthma, are associated with worse outcomes. This meta-analysis systematically quantifies the prevalence of respiratory viruses in stable and acute asthma, across children and adults, and explores factors associated with increased viral burden through meta-regression. METHODS:This prospectively registered meta-analysis (PROSPERO-CRD42023375108) included studies employing molecular techniques to assess respiratory virus prevalence in asthma. Three databases were searched in August 2024. Risk of bias and certainty of evidence were assessed. We performed random-effects meta-analysis of proportions. RESULTS:We included 111 eligible studies. Moderate-certainty evidence indicated a pooled prevalence of any respiratory virus of 33.9% (95% confidence interval 24.8-43.7%) in children and 23.0% (12.9-35.0%) in adults with stable asthma. In acute asthma, prevalence increased to 58.8% (52.5-65.0%) in children and 49.9% (41.2-58.5%) in adults (moderate certainty). Rhinovirus was the most frequently identified virus, especially in acute asthma (45.0% in children versus 21.2% in adults). Respiratory syncytial virus and bocavirus were more common in younger children, while coronavirus and influenza were more frequently detected in adults; respiratory syncytial virus peaked in older adults too. A higher prevalence of influenza virus B and adenovirus in children, and of influenza virus A and parainfluenza 2 in adults with severe versus non-severe acute asthma suggests a potential association with more severe acute attacks. CONCLUSION:Respiratory viruses are common in both stable and acute asthma. This suggests that the diagnostic value of a positive viral test during acute episodes may be limited and could benefit from complementary biomarkers to improve interpretation.

BACKGROUND:The way in which risk predictors combine and contribute to severe asthma exacerbations may differ between clinical trials and real-world settings. RESEARCH QUESTION:How do the interactive pathways of risk predictors leading to severe asthma exacerbations compare under clinical trials vs real-world settings? STUDY DESIGN AND METHODS:The analysis involved 345 patients with severe asthma from the placebo arms of 2 international randomized controlled trials (RCTs), compared with 6,814 biologic-naïve patients from the International Severe Asthma Registry (ISAR). Sixteen key risk predictors, including demographics, biomarkers, lung function, health care use, exacerbation history, long-term oral corticosteroid use, asthma control, and nasal polyps, were covered. The outcome was the occurrence of severe asthma exacerbations over the 365 days after study enrollment. Bayesian networks (BNs), obtained from machine learning combined with expert knowledge, elucidated significant interplay processes of risk predictors that led to severe asthma exacerbations. External validation was performed in each cohort. RESULTS:The RCTs revealed 44 significant arcs (ie, probabilistic interdependency) between 16 risk factors, whereas the ISAR showed 170. Despite this difference, the main downstream prediction pathways were consistent across both settings, with 2 key pathways: total serum IgE level influenced blood eosinophils to predict future severe exacerbations, and severe exacerbation history directly predicted future severe exacerbations. In external validation, RCT-BN generalized well to ISAR patients (area under the receiver operating characteristic curve, 0.68), whereas ISAR-BN underperformed in RCT patients (area under the receiver operating characteristic curve, 0.50), and ISAR-BN demonstrated better calibration. INTERPRETATION:Our results show that the core pathways predicting severe asthma exacerbations were similar in both RCTs and real-world settings, with comparable predictive performance.

BACKGROUND:A precise etiologic diagnosis of seasonal allergic rhinitis (SAR) is essential for tailored prescription of its only curative treatment, allergen immunotherapy. This is a challenging task in temperate climates, where most patients are polysensitized to multiple pollen with overlapping seasons. OBJECTIVE:The study aimed to develop a modular, flexible, and validated clinical decision support system (CDSS) generated with artificial intelligence for etiologic diagnosis of SAR. METHODS:Within the @IT-2020 project, we developed a CDSS for SAR etiologic diagnosis, automated through machine learning (ML). The CDSS includes 3 progressive modules: (a) clinical history and SPT, (b) plus molecular sIgE, (c) plus electronic/environmental diary. Three raters performed ML training, by identifying culprit pollen in 100 SAR patients (Rome, Italy) using guidelines and a Delphi-like process. RESULTS:Best-performing ML models for each diagnostic module realibly replicated expert diagnosis (area under the receiver operating characteristics curve >95%). Their validity was confirmed by: (A) contextual adaptability, with performance linked to patient complexity; (B) interpretability, as clinical features and sensitization patterns contrtibuted to predictions (SHAP analysis); (C) geographical generalizability, with consistent performance in 92 patients from Tirana (Albania); (D) temporal generalizability, maintaining high performance with reduced monitoring (45 days); (E) AIT prescription adaptability, reproducing gold-standard prescriptions; and (F) human-plus capability, ouperforming 24 physicians in a diagnostic challenge. CONCLUSION:In this proof-of-concept study, an ML-based modular CDSS reliably replicated raters' diagnosis and AIT prescription in SAR. Further studies should confirm replication and prospectively asses CDSS role in enabling SAR personalized treatment and improving disease control.

Purpose:Time to biologic initiation for the treatment of severe asthma (SA) is affected by many factors, including ease of access to biologics, which is often subject to approval by regulatory authorities and reimbursement criteria by relevant agencies. We investigated the association between ease of biologic access (using the biologic accessibility score [BACS] as a proxy) and post-biologic asthma outcomes, including remission. Methods:This ecological study, using data from CHRONICLE (a US severe asthma registry), the International Severe Asthma Registry (ISAR), and the Optimum Patient Care Research Database (OPCRD), included patients with SA from 21 countries. Associations at the country level, between BACS, a composite score of prescription criteria for biologics in SA, and the proportion of patients with a favorable asthma outcome 1-year post-biologic in each setting (ie ISAR country or in the CHRONICLE or OPCRD datasets) were tested. Several definitions of favorable outcome were used, including proportion of patients who achieved clinical remission (defined using 2, 3 and 4 domains), experienced no exacerbations, had well- or partly controlled asthma, a percent predicted forced expiratory volume in 1 second (ppFEV1) or percent predicted peak expiratory flow rate (ppPEFR) ≥80%, and no long-term oral corticosteroid (LTOCS) use. Results:A total of 9,183 patients were included. A higher BACS (as a proxy of easier access to biologics) was associated with a higher likelihood of achieving clinical remission (p≤0.001), no exacerbations (p<0.001), well- or partly controlled asthma (p=0.047), a ppFEV1 or ppPEFR ≥80% (p=0.004), and no need for LTOCS (p=0.045) 1 year post-biologic initiation. Conclusion:Easier access to biologics for patients with SA, a prerequisite for shorter time-to-initiation, was associated with a greater probability of achieving clinical remission and other favorable asthma outcomes. Initiating biologics earlier in the asthma disease course may help unlock greater therapeutic potential in SA. These findings warrant confirmation in additional studies to further establish the causal relationship between biologic accessibility, timing of initiation, and clinical outcomes in SA.

ABSTRACT Allergic Rhinitis and its Impact on Asthma (ARIA) was, up until 2017, a guideline using the best evidence (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) and developed as a change management strategy. A second change management strategy—in collaboration with the European Academy of Allergy and Clinical Immunology (ARIA‐EAACI)—was developed as a person‐centred, digitally enabled, artificial intelligence‐assisted care (person‐centred care) with strong political involvement. The digital tools of ARIA are mainly based on MASK‐air, an Organisation for Economic Co‐operation and Development (OECD) Best Practice for integrated care for chronic diseases. Artificial intelligence was used, in particular, to approach the patients' views and expectations. The current paper describes the steps to build and achieve a new change management strategy. The future of the Change Management strategy is (i) a collaboration between ARIA and EAACI, (ii) the development of ARIA 2024‐2025 guidelines, (iii) the new ARIA‐MeDALL classification of multimorbid airway diseases and (iv) embedding MASK‐air in a registry for severe allergic diseases. The ultimate goals of the ARIA‐EAACI change management strategy will be (i) the transformation of health and care in rhinitis and asthma multimorbidity and (ii) the development of novel guidelines and policies in a cost‐effective manner, improving shared‐decision‐making.

BACKGROUND:Severe asthma (SA) is associated with frequent exacerbations and high treatment costs. OBJECTIVES:To develop and validate an individualized risk calculator for severe exacerbations in SA, and evaluate its clinical utility for guiding personalized clinical decisions. METHODS:Patients with SA were identified from combined data from the International Severe Asthma Registry (2015-2022) and NOVEL observational longiTudinal studY (2016-2023) across 30 countries and regions. The prediction end point was the 12-month risk of 1 or more or 2 or more severe exacerbations. Using expert input and Bayesian network analysis, 11 routinely measured predictors were identified, measured within the past 12 months. A mixed-effects, zero-inflated negative binomial model was developed, adjusting for between-country variability and biologic drop-in effects. Internal-external cross-validation was performed using the natural clustering by country settings. RESULTS:Data from 9911 patients with SA were used. Essential predictors included age, sex, past 12-month severe exacerbations, asthma control, chronic rhinosinusitis, FEV1 to forced vital capacity ratio, percent predicted FEV1, blood eosinophils, fractional exhaled nitric oxide, and long-term oral corticosteroid and macrolide use. The model also adapted setting-specific baseline risks. In the internal-external cross-validation, across broad geographical and health care variability, the model showed excellent calibration and informative, generalizable discrimination (pooled area under the time-dependent receiver-operating characteristics curve of 0.63 [95% CI, 0.60-0.66] for ≥1 and 0.68 [95% CI, 0.64-0.72] for ≥2 exacerbations). Decision curve analysis showed clear net benefit across risk thresholds. CONCLUSIONS:The Risk of Exacerbation in Severe Asthma model quantifies SA exacerbation risk using routinely available predictors and demonstrates potential clinical utility.

Background Asthma remission has emerged as a potential therapeutic goal. However, definitions of remission have primarily focused on adult populations, with limited consensus on how remission should be defined in children. Objective To comprehensively review how asthma remission has been defined in children and to evaluate consistency and applicability of these definitions. Methods This scoping review was conducted following PRISMA-ScR guidelines. PubMed MEDLINE was searched for studies published between January 2010 and February 2024. Eligible studies included children with asthma and reported definitions of remission. Key remission criteria were extracted and categorized, and hierarchical cluster analysis was used to identify key patterns. Results Twenty-nine studies met the inclusion criteria. Most (79.3%) defined paediatric asthma remission based on the absence of clinical symptoms. The most common remission timeframe ranged from 1 to 2 years. A medication-free criterion was used in 68.9% of studies. On-treatment remission was reported in the minority of studies, but it is increasingly acknowledged as a valid outcome. Objective assessments, such as normal lung function (21%) and absence of bronchial hyperresponsiveness (10.3%), were infrequently included. Cluster analysis revealed 3 main patterns for remission definition: symptom-based, event-based, and 1 including objective criteria. Conclusion Current definitions of asthma remission in paediatric populations are predominantly symptom-based, with limited inclusion of objective physiological measures. Establishing consensus-based definitions for remission tailored to paediatric populations is essential to ensure clinical relevance and alignment with real-world disease patterns.

BACKGROUND:Allergic rhinitis is the most common chronic disease in children. Information on efficacy and safety of oral allergic rhinitis treatments in children is scarce. We aimed to comprehensively evaluate the efficacy and safety of oral medications for allergic rhinitis in children. METHODS:We performed a systematic review, searching three bibliographic databases and clinicaltrials.gov for randomized controlled trials assessing the use of oral antihistamines (OAH) or leukotriene receptor antagonists (LTRA) in children (<12 years old) with seasonal or perennial allergic rhinitis. Evaluated outcomes included the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS), the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ), development of adverse or serious adverse events, and withdrawals due to adverse events. We performed network meta-analysis at both class and individual treatment levels. Certainty in the body of evidence was assessed using the GRADE approach for network meta-analysis. RESULTS:We included eight primary studies with 906 participants. Overall, OAH were more effective against placebo in improving the TNSS (mean difference (MD) = -1.60; 95%CI = -2.25 to -0.95). On the other hand, OAH+LTRA did not demonstrate additional benefit over OAH in improving the TNSS (MD = -0.15; 95% CI = -1.18 to 0.88), and there were no important differences between individual OAH. Evidence on the TOSS was not found. No significant differences in the frequency of adverse events were observed. Certainty of evidence was low or very low for most comparisons. CONCLUSIONS:Oral treatments for allergic rhinitis appear to be effective and safe in children. However, evidence is scarce and the quality of evidence is mostly low. We performed a systematic review of randomised controlled trials assessing oral medications for allergic rhinitis in children and reporting results on nasal symptoms, ocular symptoms, quality of life and adverse events. Oral antihistamines (OAH) were found to be better than placebo, and OAH + oral leukotriene receptor antagonists (OLTRA) were not found to be better than OAH. We identified trivial differences between different OAH.

BACKGROUND:The consumption of plant-based food has lately largely increased, raising concerns about allergic reactions from ingredients which are currently not subject to mandatory labelling. METHODS:We analysed the frequency and severity of allergic reactions to non-mandatory labelled allergenic foods (pea, lentil, bean, chickpea, fenugreek, pine nut, sunflower-, poppy-, pumpkin seed, buckwheat) from two large European cohorts: The Anaphylaxis Registry (NORA) and EuroPrevall outpatient clinic study. Severity was assessed using the Food Allergy Severity Score (FASS) and compared with reactions to mandatory labelled allergenic foods. RESULTS:Among 589 reactions from both cohorts, sunflower seed was the most frequent trigger (n = 126). In NORA, pine nut (1.0% of food-induced allergic reactions) was most common followed by pea and buckwheat (0.7% each); in EuroPrevall, sunflower seed (1.2%), poppy seed (0.6%) and lentil (0.6%) predominated. After adjusting for age and sex, the severity of reactions to mandatory labelled seeds and legumes (excluding peanut) were not different (nFASS median: 4.39 vs. 4.43 and 4.56 vs. 4.49). Whereas, cereal-induced reactions (6.47) were significantly more severe than buckwheat (4.77). In Nora, the number of reactions to fenugreek and pumpkin seed were 7.4- and 3.7-fold higher in 2015-2022 versus 2007-2014. CONCLUSION:Non-mandatory labelled allergenic foods were identified to cause severe allergic reactions in two large European cohorts. The frequent involvement of sunflower seed, pine nut, pea and lentil, but also rising numbers of reactions to fenugreek and pumpkin seed, indicates their potential risk. These allergenic foods warrant close monitoring and consideration in future allergen labelling revisions.

BACKGROUND:Transient increases in blood eosinophils may accompany dupilumab treatment, but these increases are rarely associated with clinical symptoms, and clinical significance in children needs further assessment. OBJECTIVE:We sought to evaluate long-term efficacy and safety of dupilumab in children 6 to 11 years old with type 2 asthma who completed the VOYAGE study and enrolled in the open-label extension study EXCURSION and experienced an early increase in blood eosinophils. METHODS:This post hoc analysis assessed annualized severe exacerbation rates, change from baseline in pre-bronchodilator percent predicted FEV1 and z score, 5-item Asthma Control Questionnaire-Interviewer Administered (ACQ-5-IA) score, fractional exhaled nitric oxide, blood eosinophils and total IgE, and safety in subgroups with early eosinophil increase (children with <500 cells/μL at baseline and ≥500 cells/μL at VOYAGE week 12). RESULTS:At VOYAGE week 12, 22.4% (35/156) had ≥500 eosinophils/μL. Dupilumab reduced exacerbation rates versus placebo during VOYAGE across subgroups, with effects maintained in EXCURSION. Children switching from placebo to dupilumab also experienced consistent improvements similar to children who had been receiving dupilumab. Improvements in percent predicted FEV1 and z score, questionnaire score, fractional exhaled nitric oxide, and total IgE were observed in children with and without early blood eosinophil increases. No safety differences were observed across subgroups. CONCLUSION:Dupilumab reduced exacerbations, improved lung function and asthma control, and decreased inflammatory biomarkers in children with type 2 asthma across subgroups with and without early blood eosinophil increases up to 2 years. No differences in dupilumab safety profile were observed in children with early eosinophil increases. CLINICAL TRIAL REGISTRATION:VOYAGE: ClinicalTrials.gov Identifier: NCT02948959; EXCURSION: ClinicalTrials.gov Identifier: NCT03560466.

Allergic rhinitis (AR) is the most common chronic condition from childhood to adulthood and remains a major, often underestimated, contributor to impaired quality of life, school performance, and healthcare use. Although symptoms frequently begin early in life, pediatric AR is still underdiagnosed and inadequately treated, with important consequences for physical, emotional, and cognitive development. In this narrative review, we summarize recent evidence on the treatment of AR in children, highlighting age-specific challenges and evolving treatment concepts. International recommendations, particularly those from ARIA, support a stepwise, patient-centred approach focused on symptom control, safety, and long-term outcomes. Intranasal corticosteroids remain the cornerstone of therapy for moderate-to-severe disease, while second-generation antihistamines and intranasal antihistamines provide effective options for milder or intermittent symptoms. Fixed-dose intranasal steroid-antihistamine combinations are highly effective, providing options for children with more severe or uncontrolled AR. Allergen immunotherapy is the only disease-modifying intervention. Emerging strategies, including biologics and novel immunotherapy approaches, are promising but currently limited to specific contexts. Alongside pharmacotherapy, education, adherence support, and pragmatic environmental measures are essential to achieve sustained disease control. Ongoing gaps in the pediatric evidence-base highlight the need for age-adapted algorithms and long-term studies focusing on early intervention and disease modification.

The recent ARIA-MeDALL hypothesis proposed in 2023 that allergic rhinitis (AR) alone and allergic rhinitis and asthma (A) multimorbidity (AR + A) represent 2 distinct diseases. To improve the knowledge on this topic, we have gathered data from real-world studies using MASK-air®. According to our analyses: (i) An “extreme allergy phenotype” [A + AR + C, Conjunctivitis] was confirmed and found to be more severe (symptoms and work productivity) than single diseases alone. (ii) Patients with AR + A required more rhinitis medications, and had more severe VAS levels for nasal and ocular symptoms than those with AR alone in all countries tested. (iii) In clusters with poorly controlled AR, the frequency of co-medicating with more than 1 rhinitis drug was higher in AR + A than in AR alone. (iv) In the CONSTANCES general population cohort, a co-medication pattern (intranasal corticosteroid and oral H1-antihistamines) was associated with the presence of AR + A (vs AR alone). This co-medication pattern was associated in MASK-air® with a poorer AR control than monotherapy. (v) Patients with AR + A had different EQ-5D patterns than those with AR alone. (vi) Large differences were found between AR alone and AR + A in work impairment, resulting in higher weekly indirect costs in all OECD countries in AR + A by comparison to AR alone. Although mHealth studies are hypothesis-generating, and usually not reliable for testing or confirming hypotheses, our results are strongly in support of the nosologic distinction between A + AR and AR alone.

BACKGROUND:Oral and ocular medications are frequently used in the treatment of allergic rhinitis (AR). As part of the update of the Allergic Rhinitis and its Impact on Asthma (ARIA)-EAACI guidelines, this manuscript presents the ARIA-EAACI 2024-2025 recommendations for oral and ocular treatments. METHODS:The ARIA-EAACI 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgements and recommendations, including systematic reviews, mHealth and pharmacovigilance data as well as a survey on costs. RESULTS:Eight guideline questions concerning oral treatments for AR and three questions concerning ocular treatments were addressed. These questions led to the recommendations. Overall, these questions concern the choice between different classes of medication. They also discuss the role of oral antihistamines (OAH), leukotriene receptor antagonists (LTRA), ocular antihistamines (OcAH) and ocular mast cell stabilisers. Four questions had not been previously evaluated in ARIA guidelines, while, for the other four, there was a change in the strength or directionality of the recommendations. Overall, these guidelines recommend using intranasal corticosteroids over OAH and using OAH over LTRA. Moreover, they suggest using OAH over OcAH and suggest being against adding LTRA to OAH. Finally, considerations for choosing between different individual OAHs are presented. CONCLUSION:This ARIA-EAACI 2024-2025 article supports patients, their caregivers and healthcare professionals in choosing oral and ocular treatments for AR. Decisions on treatment should consider the clinical variability of the disease, patients' values and the affordability of medications.

BACKGROUND AND OBJECTIVES:Oral food challenge, particularly double-blind placebo-controlled food challenge (DBPCFC), is the gold standard for diagnosis of food allergy, although safety concerns limit its widespread use. Objectives: To evaluate the severity of reactions during DBPCFCs and to identify predictors of severe reactions. METHODS:DBPCFCs from the EuroPrevall outpatient clinic study were analyzed in patients reporting immediate reactions to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple, and/or peach. Patients with prior life-threatening anaphylaxis were excluded. Reaction severity (patient-reported and DBPCFC-elicited) was assessed using the Food Allergy Severity Score. A 2-step modeling strategy based on generalized estimating equations was applied to identify predictors of a positive DBPCFC, and, among positive challenges, predictors of anaphylaxis. RESULTS:Among 514 DBPCFCs performed, 190 (36.9%) were negative, 30 (5.8%) uncertain, and 294 (57.2%) positive (102 mild oropharyngeal reactions [19.8%] and 192 systemic reactions [37.4%], of which 160 were moderate and 32 severe). The 32 severe reactions comprised 30 cases (30/514 [5.8%]) with lower respiratory involvement (16/30 with cough or dyspnea) and 2 anaphylaxis with hypotension (2/514 [0.4%]). DBPCFC reactions were less severe than patient-reported reactions (P<.01). Atopic dermatitis and food-specific IgE >0.35 kUA/L predicted positivity, whereas prior reaction severity and egg challenge were predictors of anaphylaxis. CONCLUSION:While systemic reactions during DBPCFCs were frequent, severe anaphylaxis was rare, supporting the safety profile of DBPCFCs when appropriately conducted. Key predictors of reactivity include atopic dermatitis and food-specific sensitization, while prior severity points to a risk of anaphylaxis. These findings may help risk stratification and patient selection in clinical practice.