Background The phenotypic nature of multimorbidity in severe asthma is poorly understood. Our aims in this study were to define multimorbidity phenotypes and their characteristics in severe asthma across Europe by identifying and characterising co-aggregation of comorbidities. Methods Cross-sectional patient data were analysed from the pan-European Severe Heterogenous Asthma Research Collaboration: Patient Centred (SHARP) Central database of national severe asthma registries. Patients were grouped by four European regions (North, South, East, and West). Hierarchical clustering of comorbidities was applied to characterise the correlation structure of the ten commonest comorbidities within these geographical regions. Subsequent multimorbidity phenotypes (MMP) and their clinical features were then defined. Findings Data were available for 2690 severe asthma patients and 23 comorbidities from 11 countries. Three comorbidity clusters were consistently seen across the four European regions: 1) osteoporosis plus steroid-induced weight gain, 2) eczema plus rhinitis, and 3) chronic sinusitis plus nasal polyps. Four further comorbidities (obesity, bronchiectasis, gastro-oesophageal reflux disease, psychological factors) showed variable clustering. Multimorbidity was ubiquitous. Patients were assigned multimorbidity phenotypes (MMP) according to comorbidity cluster alignment. MMP sn (sinonasal-associated) and MMP u (no specific cluster alignment) were commonest. MMP ster (steroid-associated multimorbidity) had highest maintenance oral steroid (m-OCS) use, and Body Mass Index, plus worst lung function, asthma control, and asthma exacerbation frequency. MMP max (maximal multimorbidity) showed high prevalence of variably assigned comorbidities, higher m-OCS and biologic treatment needs. Interpretation Multimorbidity is common in severe asthma and can be classified into replicable novel phenotypes with characteristic clinical traits and outcomes. Recognising these phenotypes can guide better care of the ‘whole patient’ with severe asthma. Future clinical guidance should promote such understanding in order to support delivery of more effective personalised asthma care. Funding European Respiratory Society, pharmaceutical industry partners (Sanofi, TEVA, Novartis, GlaxoSmithKline, Chiesi).

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:Sensitisation to Alternaria is clinically important in asthma and rhinitis, but its life-course patterns and optimal diagnostic markers are unclear. We aimed to characterise Alternaria sensitisation trajectories from childhood to adulthood; we compared skin prick testing (SPT), whole-extract specific IgE and rAlt a 1, and assessed their longitudinal association with asthma and rhinitis in the Isle of Wight birth cohort. METHODS:Participants were assessed at 4, 10, 18 and 26 years. Alternaria sensitisation was measured by SPT (all ages) and serum IgE to whole Alternaria extract and rAlt a 1 (10, 18, 26 years). "Any Alternaria" denoted positivity to any assay. Alternaria, asthma and rhinitis trajectories (10-18-26 years) were classified as Never, Any positive or Persistent. Associations used χ2 trend tests and Poisson regression with robust errors. RESULTS:Among 434 participants with complete Alternaria data, trajectories were Never 84.1%, Any 11.1% and Persistent 4.8%. Alternaria trajectories showed graded associations with asthma, and more strongly with rhinitis (trend p < 0.001 for both), with highest risks for persistent asthma and rhinitis. Across ages, rAlt a 1 discriminated asthma risk better than whole-extract in youth, whereas effects converged by 26 years. For rhinitis, effect sizes were similar across assays and ages. Assay agreement strengthened with age, becoming substantial by 18 years and near-perfect by 26 years. CONCLUSIONS:Alternaria sensitisation consolidates from late adolescence and, when persistent, tracks with persistent asthma and rhinitis. Longitudinal analysis shows rAlt a 1 discriminates asthma risk better than whole-extract in youth, while assays are largely interchangeable in adulthood.

Background: The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) recently convened an expert consultation to address the increasing but inconsistent use of Precautionary Allergen (“may contain”) Labelling (PAL). Objectives: We conducted a Delphi study to explore the perspectives of clinicians, patient representatives, and other interest-holders on PAL practice. Methods: We followed previous guidance on Delphi study development and reporting. A narrative review exploring the FAO/WHO Expert Consultation informed the Delphi process. The working group generated 35 items based on the review of FAO/WHO consultation, categorized into 7 domains: (i) Importance of the issue, (ii) Informing use of PAL, (iii) Action level cut-offs, (iv) Communication, (v) Liability considerations, (vi) Free From statements, and (vii) Areas for further research. Items underwent 3 iterative Delphi rounds involving a panel of 35 experts who rated their agreement narratively and on a 5-point Likert scale. Consensus was defined as ≥70% consistency in agreement or disagreement (excluding neutral responses); stability was defined as <10% variation in average scores across rounds. A public consultation was held to collect different viewpoints arising from the consensus activity. Results: The Delphi was concluded after 3 rounds with consensus achieved for 33/35 items. Response rate was 100% across all 3 rounds. The panel strongly agreed that PAL should only be applied when an unintended allergen may be present above a cut-off (action level) and that it should always be based on a formal risk assessment, preferably quantitative, and mandated through legislation. Furthermore, action levels should be based on “reference doses” (amount of total allergenic protein), rather than on a concentration (eg, 10 ppm), and more specifically on population-adjusted eliciting doses ED05 (amount of allergen expected to elicit an objective reaction in no more than 5% of the allergic population). To achieve a balance between protection and the risk of PAL overuse, ED05 was deemed preferable to ED01. There was 70% agreement that consumers should be informed of residual risk (ie, unintended allergen presence below the reference dose), but no consensus as to how this might be done. Finally, PAL should not be used for an allergen declared to be absent with a “free from” statement, nor should a PAL appear for an allergen listed as an ingredient. Conclusions: This Delphi explored a comprehensive set of statements across multiple aspects of PAL development, application, and communication. On the one hand, it provides systematically derived considerations, aligned with the FAO/WHO consultation recommendations, to support future harmonization of practices. On the other, it highlights several areas of uncertainty to prioritize for future research.

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:Immunonutrition examines how diet influences immune development. Complementary feeding represents a critical window for long-term health. We aimed to map evidence linking complementary feeding to immune outcomes, allergy, infection, and growth in infants and toddlers (≤ 3 years). We conducted a scoping review and evidence-gap mapping, following PRISMA-ScR. MEDLINE and Epistemonikos were searched from inception to November 2024. Concepts included diet diversity/patterns, feeding practices/models, and timing of allergen introduction, timing of complementary feeding, macronutrients, micronutrients, foods, supplementation, and ultra-processed foods. We included systematic reviews and recent primary studies meeting criteria. RESULTS:From 13,512 records screened, 108 systematic reviews were included, comprising 99 randomized controlled trials, 41 cohorts, 22 case-control, and 14 cross-sectional studies. Most reviews addressed nutrient intake, supplementation, or timing of allergen introduction, while fewer reviews explored diet diversity, foods, or ultra-processed food intake. Responsive complementary feeding was consistently associated with healthier growth and lower obesity risk, whereas restrictive practices showed adverse effects. Greater diet diversity was linked to reduced asthma and food allergy risk, though eczema findings were inconsistent. Western-style diets high in processed foods, fat, sugar, and meat correlated with higher allergy risk, while home-prepared diets were protective. Micronutrient supplementation (iron, zinc, vitamin D) reduced infection and anemia risk but had mixed effects on allergy. Early allergen introduction reduced food allergy incidence. CONCLUSIONS:Complementary feeding research now extends beyond calorie counting, macronutrients, and early allergen introduction to dietary patterns and early life nutrition that supports the microbiome. Evidence supports dietary diversity, timely food allergen introduction, and responsive feeding, while discouraging restrictive practices and ultra-processed foods. Future work should harmonize definitions and investigate plant-based diets, advanced glycation end products, and processed food exposures.

Allergen immunotherapy (AIT) has been acknowledged as the only disease-modifying treatment for respiratory diseases since its introduction in 1911. Although the efficacy and safety have convincingly been established in numerous randomized clinical trials (RCTs), the AIT study results may vary substantially. Several factors that may influence the outcome of RCTs will be addressed. First, the choice of the primary endpoint is essential. Lack of validated endpoints with proven clinical relevance may contribute to the variation in study results. Secondly, heterogeneity of the patient population affects the study outcome, thereby raising the question of whether current selection criteria should be further optimized to capture those patients who will benefit from immunotherapy. Thirdly, variability and particularly low allergen exposure may lead to unsuccessful AIT trials. Fourthly, unsuccessful trials may stem from large placebo effects. Furthermore, discrepancies between Phase II and III studies are asking for cautious interpretation of Phase II studies when planning Phase III studies. Flaws in trial design, inadequate reporting of the clinical trial protocol and data may hamper the interpretation of study results. In addition, this review addresses specific aspects of AIT trial design in children and asthmatic patients. To improve future AIT trials, innovative solutions are urgently needed, including the establishment of an internationally accepted minimal clinically important difference (MCID), the validation of primary endpoints, the integration of field studies and allergen exposure chamber studies, and the publication of negative study results.

BACKGROUND:IgE-mediated food allergy burdens individuals, families and healthcare systems. Randomised controlled trials indicate early introduction and regular consumption of common food allergens in infancy can reduce food allergy risk. Few studies have explored parental and healthcare professional experiences. This systematic review examines their perspectives applying a theory-informed behavioural analysis identifying key barriers influencing food allergen introduction. METHOD:A systematic search of seven databases was conducted in November 2025. All study designs and published primary research papers were included and screened against the inclusion/exclusion criteria. Quantitative findings were summarised narratively and analysed alongside qualitative data. All findings were synthesised concurrently using an integrated thematic synthesis following the Thomas and Harden approach. Quality appraisal was assessed. RESULTS:Twenty-five studies were included. Four themes were identified: (1) Practical barriers to introducing the allergenic foods, (2) perceived risk and fear of allergic reactions and safety, (3) navigating and making sense of food allergy prevention information, particularly conflicting advice for parents and (4) food allergy prevention advice, guidance awareness, interpretation and implementation. CONCLUSION:Effective food allergy prevention requires early, consistent support for parents from suitably trained healthcare professionals. Advice should be evidence-based, simple, culturally relevant and accessible, promoting realistic and healthy infant and family foods and diets.

Background Immunoglobulin E-mediated (immediate) cow’s milk allergy is one of the most frequent food allergies in infants, with a significant adverse impact on quality of life. There is no satisfactory treatment for cow’s milk allergy, and guidelines recommend milk avoidance, feeding with ‘hypoallergenic’ formulas (extensively hydrolysed formulas), emergency management of accidental reactions and waiting for the allergy to resolve spontaneously. Currently, the only potentially curative regimen is oral immunotherapy, that is, exposing patients to increasing doses of cow’s milk using a strictly controlled dose schedule. However, milk immunotherapy is not used in clinical practice due to risk of reactions. DREAM’s intention was to explore whether oral immunotherapy with a partially hydrolysed cow’s milk formula would be able to provide a safe and effective means of oral immunotherapy for milk-allergic infants. Limitations The trial was affected by a serious breach that led most of the participants to receive partially hydrolysed formula, even if randomised to extensively hydrolysed formula. It also ended prematurely due to unsatisfactory recruitment, and the main outcomes were not reached. Methods DREAM was a two-arm, parallel-group, double-blind randomised controlled trial. Eligible patients were infants aged 6–12 months with convincing medical history of immunoglobulin E-mediated allergy to cow’s milk formula. Inclusion criteria included a titre of cow’s milk-specific immunoglobulin E equal or higher to 2 kU/l, or wheal equal or over 5 mm to skin prick test to milk. Additionally, for the infants to be randomised, they needed to have a positive result to an open oral challenge either to partially hydrolysed formula or to milk. Participants were randomised to extensively hydrolysed formula or partially hydrolysed formula with a 1 : 1 ratio. Following randomisation, participants commenced free-feeding with the blinded product (or strict dose-based oral immunotherapy if they were not tolerant of the blinded product). The main outcome was the result of a double-blind, placebo-controlled food challenge to cow’s milk at the end of 1 year of free-feeding (or of dose-based immunotherapy) to establish if infants had become tolerant. As the trial was discontinued early on account of poor recruitment, no infant progressed to the double-blind, placebo-controlled food challenge. Results Out of 16 randomised participants who underwent an initial partially hydrolysed formula challenge, only 1 (6.25%) reacted to it (95% confidence interval 00.0 to 19.6). Hence, 93.75% of the allergic infants randomised in the trial tolerated partially hydrolysed formula. All fifteen infants that were found to be partially hydrolysed formula-tolerant also received partially hydrolysed formula free-feeding at home, on account of the serious breach. As per the trial’s criteria, these infants (and all randomised participants) were shown to be allergic to cow’s milk via either a positive open challenge to it (for the 15 partially hydrolysed formula-tolerant infants) or a positive open challenge to partially hydrolysed formula (for the single partially hydrolysed formula-reactive infant). Conclusions Partially hydrolysed formula was tolerated by the majority of well-characterised and confirmed cow’s milk-allergic infants in the DREAM trial. Future work Our findings demonstrate that partially hydrolysed formula holds promise as a potential oral immunotherapy medium in free-feeding oral immunotherapy regimens in future research. Further trials designed on the premise of partially hydrolysed formula oral immunotherapy are needed. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number 17/60/44. Plain language summary Cow’s milk allergy is one of the most frequent food allergies in infants. There is no known cure for cow’s milk allergy, and allergic infants need to avoid cow’s milk, feed with ‘hypoallergenic’ formulas (if not solely breastfeeding) and wait for the allergy to go away on its own. The only potentially helpful management is oral immunotherapy, where some infants eat very low regular doses of milk under close doctor follow-up. However, immunotherapy is risky, and many reactions can happen; therefore, it is not normally advised to patients. DREAM was designed to show whether using a particular formula (partially hydrolysed cow’s milk formula) would be safe for immunotherapy. Milk-allergic infants aged 6–12 months were recruited and started to be fed on either extensively hydrolysed formula (safe formula used normally for allergic infants) or partially hydrolysed formula. These infants could also be breastfed, if their mother wanted to. The mother’s diet was not changed. After a year of feeding, also including several visits at the hospital, infants would be given cow’s milk at the hospital to see if they have managed to tolerate cow’s milk after having these formulas for a whole year. Unfortunately, the trial was stopped early due to not managing to recruit as many infants as needed, and therefore no infant reached the end of the trial. Out of 16 infants which did enter the trial, 15 (close to 94% of all infants) were able to have partially hydrolysed formula with no major problems. These infants were shown through the trial’s tests to be very allergic to cow’s milk; therefore, being able to have partially hydrolysed formula with little problem is very important. The trial managed to show that partially hydrolysed formula is promising for future immunotherapy management, because many milk-allergic infants were able to feed on it. More research is needed to show if this formula can be used in the future to help infants grow out of their allergy.

Health care providers across settings must be trained to manage anaphylaxis by (1) removing the offending allergen if still present; (2) positioning the patient with legs elevated, and if respiratory distress is present, allow the patient to sit upright with legs extended and elevated; (3) immediately administering epinephrine (adrenaline) intramuscularly (IM) or intranasally (IN) every 5 to 15 minutes for persistent anaphylaxis; and (4) optimizing airway, breathing, and cardiovascular (ABC) resuscitation. This may include supplemental oxygen, noninvasive or invasive positive-pressure ventilation, and intravenous fluid resuscitation. For life-threatening or refractory presentations, (5) IM/IN epinephrine should be administered every 5 minutes while addressing ABC derangements; this includes aggressive intravenous fluid resuscitation for patients in anaphylactic shock. Providers may continue IM or IN epinephrine or switch to the other, as both routes are considered equally efficacious based on pharmacokinetic data. An intravenous epinephrine infusion should be prepared for patients with persistent anaphylaxis after 2 doses of IM/IN epinephrine and initiated after the third dose, or earlier at the provider's discretion. In settings without epinephrine infusions, repeat IM/IN epinephrine should be administered every 5 minutes, along with other ABC interventions, and the patient should be transferred quickly to a setting equipped to provide advanced resuscitative care.

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.

INTRODUCTION:Using the James Lind Alliance (JLA) methodology, we established a Priority Setting Partnership (PSP) to identify the most important unanswered research questions in childhood food allergy. This approach places those directly affected, those with food allergy, their parents/carers, and healthcare professionals at the centre of the process. METHODS:A multidisciplinary steering group (n = 19 people) oversaw the PSP. Research uncertainties were collected through a UK-wide online survey distributed to children, young people and adults with food allergy, their parents/carers, and healthcare professionals working in food allergy. A focus group was conducted with seven children aged 8-11 years with food allergy to ensure inclusion of their perspectives. Submitted questions were reviewed, combined into summary questions, and checked against existing evidence to confirm that they represented genuine uncertainties. An interim prioritisation survey was used to rank questions, with equal weighting given to each stakeholder group. A final facilitated workshop used a nominal group technique to agree on the top 10 research priorities. RESULTS:In total, 916 respondents submitted 2563 questions. After removing out-of-scope and already answered questions, an interim prioritisation survey was completed by 1087 participants. The final workshop involved 29 participants, including young people (n = 3), young adults (n = 4), parents (n = 7) and multidisciplinary healthcare professionals (n = 15), who agreed on the top 10 questions. These cover prevention, early diagnosis, treatment, causes, eating out, safety in care settings, impact, emergency treatment, and awareness of food allergy. There was strong consensus from the final workshop across all attendees that prevention should be the number one priority. CONCLUSION:Using a rigorous, transparent, and person-centred approach, we have identified the most important research priorities in childhood food allergy. They highlight the depth and breadth of research required to improve the prevention, diagnosis, treatment, and broader impacts of food allergy on children, families, and carers who live with this condition.

Background:Wheeze and lung function (LF) during childhood are key indicators of respiratory health, yet their trajectories are usually examined separately. We aimed to identify joint developmental patterns of wheeze and LF. Methods:We used data from four unselected birth cohorts established between 1989 and 1996 with repeated assessments of wheeze from infancy and spirometry from early school-age to early adulthood. We used group-based multi-trajectory modelling to derive trajectories based on joint modelling of current wheeze and forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC). Findings:In the discovery analysis (n = 4645), we identified 6 trajectories: (1) Never/infrequent wheeze with normal LF (NIFW-NLF, 2925/4645 [62.97%]); (2) Never/infrequent wheeze with reduced LF (NIFW-RLF, 475/4645 [10.22%]); (3) Early-transient wheeze with normal LF (ETW-NLF, 559/4645 [12.03%]); (4) Late-onset wheeze with NLF (LOW-NLF, 335/4645 [7.21%]); (5) Persistent wheeze with NLF (PEW-NLF, 202/4645 [4.34%]); and (6) PEW with RLF (PEW-RLF, 149/4645 [3.21%]). Risk profiles of two trajectories characterised by persistent wheeze but differentiated by normal or reduced LF differed significantly. Elevated fractional exhaled nitric oxide (FeNO) and allergic sensitisation were highly prevalent in both, but only PEW-RLF was significantly associated with perinatal and early-life factors/exposures (prematurity; lower gestational age: RRRs [95% CI] 2.21 [1.49-3.28], low birth weight: 2.60 [1.47-4.60]: and exposure to smoking during gestation: 2.00 [1.49-2.63]). Two low lung function trajectories (with and without symptoms; PEW-RLF and NIFW-RLF) had similar LF impairment, but divergent clinical and risk factor profiles. PEW-RLF was associated with high rates of asthma diagnosis, high FeNO, bronchodilator reversibility, and family history of atopy. In contrast, those in NIFW-RLF trajectory had no elevation in inflammatory biomarkers and low prevalence of airway hyperreactivity, and were characterised by much higher rates of prenatal tobacco smoke exposure, and greater active adolescent smoking (2.06 [1.41-3.01]), and higher body fat mass in adolescence (1.02 [1.01-1.03], p = 0.01) with no difference in birth weight or preterm birth. Replication analyses in independent cohorts (n = 3388) were consistent with the discovery. Interpretation:The disconnect between symptoms and lung function, along with the differences in risk profiles, has important implications for respiratory health intervention strategies. Funding:UK MRC grant MR/S025340/1.

Background:Multimorbidity refers to the presence of multiple coexisting conditions, but is often underappreciated in the context of severe asthma (SA) management. We sought to identify differences in approaches to multimorbidity management in SA, variability in access to multidisciplinary team (MDT) resources, and whether physician perspectives on multimorbidity differ between SA specialists and general respiratory physicians. Methods:The Severe Heterogeneous Asthma Registry, Patient-centred (SHARP) Clinical Research Collaboration circulated an online physician survey via European national respiratory societies to assess 1) available resources to address multimorbidity and 2) physician perspectives on multimorbidity in SA. Results:495 responses from 25 European countries included 48% SA specialists and 52% general respiratory physicians. SA specialists had more experience with SA patients (20% were seeing >60 patients per month) compared to general respiratory physicians. SA specialists had greater access to multidisciplinary care - including better access to MDTs, allied health professionals and referrals to external specialists, and therefore more routinely assessed comorbidities and considered them greater influences on their practice. They also considered multimorbidity to a greater degree and rated its impact on their patients' asthma outcomes (and general health outcomes) as more substantial. Conclusions:Alongside more experience of treating SA, SA specialists have increased awareness of multimorbidity and better resources to manage it. However, access to MDTs remains a significant gap for both SA specialists and general respiratory physicians. Furthermore, both groups identified a high need for further education and training about multimorbidity. These findings highlight key areas for improvement in clinical practice, resources and training.

BACKGROUND:Early identification of children at risk of asthma attacks is important for optimizing treatment strategies. We aimed to integrate salivary microbiome and serum inflammatory mediator profiles with asthma attacks history to develop a comprehensive predictive model for future attacks. METHODS:This study contained a discovery (SysPharmPediA) and a replication phase (U-BIOPRED). School-aged children with asthma were classified into at risk and no-risk groups, based on the presence or absence of one or more severe attacks during one-year follow-up. Prediction models were developed using random forest on the training set (70%) with data on past asthma attacks, microbiome composition, serum inflammatory mediator levels, and their combinations and then tested on the rest of the population (30%). Outcomes were replicated in a subset of children with severe asthma from U-BIOPRED. RESULTS:Complete data were available for 154 children (SysPharmPediA = 121, U-BIOPRED = 33). In discovery, the model based on past attacks resulted in an area under the receiving characteristic curve (AUROCC) ~ 0.7. Models including six salivary bacteria or six inflammatory mediators achieved similar results. The combined model incorporating seven features, past asthma attacks, Capnocytophaga, Corynebacterium, and Cardiobacterium, TIMP-4, VEGF, and MIP-3β achieved the highest accuracy with AUROCC ~0.87. The combined model in the U-BIOPRED limited to available inflammatory mediators (VEGF), and incorporating past asthma attacks, Capnocytophaga, Corynebacterium, and Cardiobacterium, resulted in an AUROCC of 0.84. CONCLUSION:Serum inflammatory mediators and salivary microbiome complement asthma attacks history for predicting future attacks. These results highlight the imperative for continued investigation into oral microbiota and its interaction with the immune system.

Background Lung function during childhood is an important predictor of subsequent health and disease. Understanding patterns of lung function and development of airflow limitation through childhood is necessary to inform lung function trajectories in relation to health and chronic airway disease. We aimed to derive trajectories of airflow limitation from childhood (age 5-8 years) into early adulthood (age 20-26 years) using repeated spirometry data from birth cohorts. Methods In this study, we drew forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) data from six population-based birth cohorts: the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), Isle of Wight cohort (IOW), Manchester Asthma and Allergy Study (MAAS), and Aberdeen Study of Eczema and Asthma (SEATON) as well as the Swedish Child (Barn), Allergy, Milieu, Stockholm, Epidemiological survey (BAMSE) and the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. For the discovery analysis, we pooled data from ALSPAC, IOW, MAAS, and BAMSE with spirometry data recorded at middle childhood (age 8-10 years), adolescence (age 15-18 years), and early adulthood (age 20-26 years). For the replication analysis, we pooled middle childhood and adolescence spirometry data from PIAMA and SEATON. We used latent class trajectory modelling to derive trajectory classes based on joint modelling of FEV1 and FEV1/FVC ratio regression residuals ascertained from all age groups. The final model was selected using the lowest Bayesian information criterion. Participants were assigned to the trajectory with the highest posterior probability. Weighted random-effect multinomial logistic regression models were used to investigate factors associated with joining each trajectory, the results of which are reported as relative risk ratios (RRRs) with 95% CIs. Findings The discovery population included 8114 participants: 4710 from ALSPAC, 808 from IOW, 586 from MAAS, and 2010 from BAMSE and was modelled into one of four lung function trajectories that showed normal airflow (6555 [808%] of 8114 people), persistent airflow obstruction (1280 [158%]), worsening airflow obstruction (161 [20%]), and improved airflow obstruction (118 [15%]). Both improvement in and worsening airflow obstruction by early adulthood were seen from all initial severity levels. Whereas improvement in airflow obstruction was more prominent between middle childhood and adolescence (578%) than between adolescence and early adulthood (134%), worsening airflow obstruction was more prominent between adolescence and early adulthood (615%) than between middle childhood and adolescence (326%). Among current wheezers, higher BMI was associated with a lower relative risk of joining the trajectory with improvement in airflow obstruction (RRR 069 [95% CI 049-095]), whereas among non- wheezers, higher BMI increased the relative risk of being in the improved airflow obstruction trajectory (138 [104-185]). A higher BMI at first lung function assessment was associated with a higher relative risk of joining the trajectory for improvement in airflow obstruction trajectory in participants with low birthweight and no current asthma diagnosis (RRR 244 [117-512]); by contrast, higher BMI is associated with a lower relative risk of joining the trajectory with improvement in airflow obstruction among those with low birthweight and current asthma diagnosis (037 [018-076]). Results in replication cohorts (n=1337) were consistent with those in the discovery cohort. Interpretation Worsening and improvement in airflow limitation from school age to adulthood might occur at all ages and all airflow obstruction severity levels. Interventions to optimise healthy weight, including tackling overweight and obesity (particularly among children with wheezing) as well as treating underweight among non-wheezers, could help to improve lung health across the lifespan.

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes. Objective: We sought to develop a consensus anaphylaxis definition, overview, and clinical support tool. Methods: A 12-member writing group developed draft outputs modified with input from a 46-member international expert panel, 31 medical stakeholder organizations, and 15 patient advocacy organizations. The expert panel participated in a modified Delphi process to seek consensus for the outputs using a >= 80% consensus threshold. Results: The first sentence of the definition reads, "Anaphylaxis is a serious allergic (hypersensitivity) reaction that can progress rapidly and may cause death." The definition also describes organ systems that may be involved and signs of life-threatening reactions. The overview includes details of anaphylaxis recognition and management. The clinical support tool incorporates new clinical criteria to help determine the likelihood that patients are having anaphylaxis, intramuscular epinephrine indications and dosing, and common findings from the anaphylaxis organ systems. In addition, 93.5% (43/46), 97.8% (45/46), and 93.5% (43/46) of experts agreed with the definition, overview, and clinical support tool, respectively. Conclusion: The anaphylaxis overview is a novel educational tool conveying key elements of anaphylaxis recognition and management. We propose that the definition and clinical support tool should replace previous definitions and clinical criteria. The clinical support tool should facilitate improved anaphylaxis recognition and management across different clinical settings and standardize research outcomes.

Background Allergic rhinitis (AR) impacts quality of life, work and school productivity. Over the last years, an important body of evidence resulting from mHealth data has led to a better understanding of AR. Such advances have motivated an EAACI-endorsed update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (ARIA 2024-2025). This manuscript presents the ARIA 2024-2025 recommendations for intranasal treatments, one of the mainstays for AR management.Methods The ARIA 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 judgments and recommendations, including systematic reviews, evaluation of mHealth and pharmacovigilance data, as well as a survey of experts on costs.Results Eleven guideline questions concerning intranasal treatments for AR were prioritized, leading to recommendations. Overall, these questions concern the choice between different classes of intranasal medications-most notably, intranasal corticosteroids (INCS), antihistamines (INAH), fixed combinations of INAH+INCS and decongestants-or between different individual medications within each class. Four questions had not been evaluated in previous ARIA guidelines, while for the other three there was a change in the strength or directionality of recommendations. Overall, recommendations point to the suggested use of INAH+INCS over INAH or INCS and INCS over INAH.Conclusion This ARIA 2024-2025 article supports patients, their caregivers, and healthcare professionals in choosing an intranasal treatment. However, decisions on AR treatment should consider the clinical variability of the disease, patients' values, and the affordability of medications.