Background: Clinical remission is an emerging therapeutic goal in severe asthma treated with biologics. However, remission may evolve beyond the conventional 12-month assessment, and limited real-world data are available on patients who continue the same biologic after incomplete remission at 12 months. We evaluated longitudinal remission trajectories in patients with severe T2-high asthma continuing the same biologic therapy. Methods: This retrospective real-world single-center SANI cohort included adults with severe asthma treated with one biologic agent and followed for at least 18 months. Clinical outcomes and remission status were assessed at 12 and 18 months according to the SANI definition, distinguishing complete remission, partial remission, and no remission. Results: The cohort included 146 patients; 64.4% were female, median age was 61 years, and all had a T2-high phenotype. Maintenance oral corticosteroid use decreased from 83.6% at baseline to 6.8% at 18 months, while symptomatic patients decreased from 100.0% to 11.0%. Median ACT improved from 12.0 to 22.0, and patients with ≥1 exacerbation decreased to 4.1% at 18 months. Complete remission increased from 36.3% at 12 months to 67.1% at 18 months, while no remission decreased from 54.1% to 16.4%. Among patients not in remission at 12 months, 43.0% achieved complete remission and 26.6% achieved partial remission at 18 months. Baseline oral corticosteroid use was associated with lower remission likelihood, whereas preserved baseline FEV1 favored remission at 18 months. Conclusions: Among patients with severe T2-high asthma selected for continuing an unchanged biologic for at least 18 months, remission status was more favorable at 18 months than at 12 months. This observation describes the trajectory of biologic continuers and should not be generalized to all patients who remain outside remission at 12 months. Because patients who discontinued or switched biologics were excluded, these data do not establish that continuation is preferable to switching after an incomplete 12-month response.

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.

BackgroundHypereosinophilic Syndrome (HES) is a rare disorder with a heterogeneous clinical presentation. If not recognized, it can lead to diagnostic delay and worse prognosis. Our study aimed to describe the real-world scenario of patients presenting with hypereosinophilia (HE), diagnosed with HES in an Italian Immunology Excellence University Centre. In addition, we also assessed the feasibility of a two-tailed approach for HES diagnosis, which consists of proceeding from the beginning with the differential diagnosis and systematic evaluation of organ damage.MethodsA retrospective observational single-center study was conducted. All patients underwent blood and instrumental tests to simultaneously identify HES etiology and any organ damage, through a process we called the “two-tailed approach”.ResultsTwo hundred forty-seven patients with HE referred to our center underwent the two-tailed approach. Due to either the presence of a straightforward underlying disease associated with HE, or the lack of sustained hypereosinophilia, 168 patients (68.0%) were excluded from the study. Seventy-nine patients (31 females, 39.2%) with a mean age of 54.9 years were finally diagnosed with HES. 19 (24.1%) patients were diagnosed with reactive HES, 15 (19.0%) with overlap HES, 1 (1.3%) with myeloid-HES, 10 (12.7%) with lymphocytic HES, and 8 (10.1%) with idiopathic HES. Sixty-three patients showed involvement of at least two organs: the lung (32/63, 50.7%), the skin (24/63, 38.1%), the bowel (23/63, 36.5%), and the peripheral nervous system (25.4%). Eight patients (8/63, 12.7%) showed heart involvement. The diagnosis was achieved in 4 ± 1.8 months, and no deaths were observed.ConclusionHE is a common reason for consultations with allergists and clinical immunologists, and the two-tailed approach, which tests simultaneously for diagnosis and organ damage, should be implemented from the initial evaluation of patients with HE. The lower rate of idiopathic HES diagnosis and the higher frequency of heart involvement we found confirm the usefulness of the tool in reducing the risk of mistakes in classifying HES subtypes and the diagnostic delay, thus allowing prompt and tailored treatment and better outcomes.

Oxidative stress in the intestine, if not counteracted by an antioxidant-rich diet, can generate new substances called pseudoleukotrienes (ØLTs). These ØLTs appear to activate inflammatory signals and immune cells (like mast cells and type 2 helper T cells), potentially increasing the risk of an allergic reaction in sensitized individuals. Recent research highlighted the role of an intestinal enzyme, Dipeptidase 1 (DPEP1), which can protect against severe anaphylaxis by degrading leukotrienes, key mediators of allergic reactions. Enriching the modern diet with polyphenols could be an effective strategy to counteract oxidative stress and prevent or mitigate food allergies. Developing drugs that prevent the free radical process at intestine level as well drugs which block the generation of LTs by intestinal mast cells may represent new pharmacological approach to the treatment of food allergy.

[This corrects the article DOI: 10.1016/j.waojou.2025.101095.].

IntroductionHypereosinophilic syndrome (HES) is defined by persistent hypereosinophilia Q5 associated with eosinophil-mediated organ damage. However, the relationship between HES etiology and organ-involvement patterns remains incompletely defined, particularly in non-hematological forms. This study aimed to describe organ involvement across HES subtypes and to explore clinical associations with multiorgan disease. MethodsIn this retrospective single-center study, 105 patients referred for hypereosinophilia were classified after a standardized two-tailed diagnostic work-up as reactive HES, single-organ HES, lymphocytic-variant HES (L-HES), overlap HES, idiopathic HES, myeloid HES, or HEus. Demographic data, absolute eosinophil count (AEC) at onset, organ domains, organ burden, and exploratory associations with multiorgan disease were analyzed. ResultsMean age at onset was 54.6 ± 18.9 years, and 60.0% of patients were male. Thirteen patients were classified as HEus and had no detectable organ involvement, whereas all HES categories showed at least one involved organ domain. Among recorded organ domains, lung involvement was the most frequent (39.0%), followed by gastrointestinal (30.5%) and cutaneous involvement (29.5%). Peripheral nervous system involvement occurred in 19.0% of patients, whereas cardiac, renal, thrombotic, and central nervous system involvement occurred in 6.7%, 4.8%, 1.9%, and 1.0%, respectively. Multiorgan involvement occurred in 34 patients (32.4%).DiscussionOrgan burden differed significantly across subtypes, with overlap HES, mainly driven by eosinophilic granulomatosis with polyangiitis (EGPA), showing the highest multiorgan burden. L-HES and idiopathic HES were predominantly associated with cutaneous disease, whereas single-organ HES involved only the gastrointestinal tract or lung. AEC correlated with the number of involved organs and was strongly associated with multiorgan involvement. Organ involvement in HES is common, heterogeneous, and unevenly distributed across subtypes. Integrating etiological classification with systematic organ phenotyping may improve risk stratification and guide diagnostic and follow-up strategies.

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.

Background: The COVID-19 pandemic significantly increased the demand for allergy consultations to evaluate the risk of hypersensitivity reactions in patients either before receiving their first dose of an anti-SARS-CoV-2 vaccine (Group 1) or following suspected allergic reactions after vaccination (Group 2). Methods: We conducted a retrospective analysis of patients referred to the Immunology and Allergy Unit of the Azienda Ospedaliera Ordine Mauriziano in Turin, Italy, between December 2020 and December 2022. Risk assessment was performed according to Italian and European guidelines, and allergy skin tests were administered when necessary. Patient data were cross-referenced with the SIRVA platform (Regional Vaccination Management Information System) to assess vaccine eligibility, administration, and outcomes. Results: A total of 1222 patients were evaluated (mean age: 52 years; female-to-male ratio 4:1). In Group 1 (n = 914), 137 patients (15%) underwent skin testing, of whom 15 (1.6%) tested positive. Vaccination was recommended for 899 patients (98%), though 184 (20%) did not proceed. Among those vaccinated, 679 (74%) received additional doses, with 48% receiving a third and 11% a fourth dose. In Group 2 (n = 308), 104 patients (33%) underwent skin testing, with 9 (8%) testing positive. Vaccination without restrictions was recommended for 299 patients (97%), but 45 patients (15%) did not proceed. Among the remaining, 262 (85%) received a second dose, 183 (59%) a third, and 29 (9%) a fourth dose. Overall, 1198 patients (98%) had no specific contraindications to vaccination. Only 5 patients (0.4%) were completely exempted from vaccination due to confirmed sensitivity to both polyethylene glycol (PEG) and polysorbate 80 (PS80). An alternative vaccine was recommended for 19 patients; 16 of them proceeded with vaccination and tolerated it without adverse effects. Conclusions: Our findings demonstrate that the majority of high-risk allergic patients can safely receive anti-SARS-CoV-2 vaccines following allergological evaluation. The rate of confirmed excipient allergy was very low, and vaccine adherence was comparable to the general population. This is, to our knowledge, the first study to longitudinally assess the number and types of vaccine doses administered to high-risk allergic individuals.

Asthma is characterized by chronic airway inflammation that underlies exacerbations in response to environmental triggers. The notable change in the environment that has occurred in recent decades, both outdoor and indoor, has contributed to increasing the concentrations of substances considered toxic to epithelia, including the epithelium of the airways. Considering the importance of environmental triggers, an avoidance strategy for environmental triggers could be useful for improving asthma control with sparing use of medications. The purpose of this commentary is to provide evidence that avoidance of environmental triggers can help control asthma with a consequent saving of anti-asthma medications. This approach requires that monitoring of pollutants to which the patient is exposed becomes part of the patient evaluation as is the search for biomarkers of inflammatory response. Many observations have shown that reduced exposure to NOx, household cleaning products and fine particulate matter is able to improve asthma control. Equally important for the control of asthma were the remediation of houses with damp and mold. Greater consideration of the environmental triggers of asthma exacerbations can help the clinician further personalize the asthma treatment strategy. The message is to combine the immunophenotyping of asthma (T2 high vs. T2 low) with a sort of phenotyping of environmental triggers.

Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterised by persistent hypereosinophilia associated with organ damage. Due to its rarity and heterogeneity in its clinical presentation, HES remains underdiagnosed or misdiagnosed, often leading to delayed diagnosis and irreversible organ damage. The complexity of HES diagnosis is even more complicated due to the absence of standardised criteria. Moreover, the lack of structured referral pathways among specialists, including allergists, clinical immunologists, haematologists, and rheumatologists, further hinders optimal patient care. To address these challenges, the Italian National Hypereosinophilic Syndrome (INHES) Network aimed to enhance the diagnosis, management, and research of HES. INHES objectives also include connecting specialised centres, facilitating data collection on HES and eosinophilic-associated conditions, and improving healthcare standards through consensus guidelines. To do this, INHES has created a web-based platform called “Phleos” to develop a comprehensive referral map, ensuring timely and appropriate patient access to expert care. Phleos is a web-based datasheet, per GDPR regulations, to systematically collect anonymised clinical data, including absolute eosinophil counts, organ involvement, laboratory parameters, instrumental assessments, and treatments. A structured classification system enables differentiation among idiopathic, lymphocytic, myeloid, familial, reactive, and overlap forms of HES. Moreover, the platform integrates standardised diagnostic pathways and treatment protocols to harmonise patient care across participating centres. The INHES Network aims to mitigate diagnostic delays, optimise therapeutic decision-making, and advance research in eosinophilic disorders by fostering interdisciplinary collaboration and establishing a unified framework. This initiative represents a crucial step toward a cohesive national strategy, ultimately improving clinical outcomes for HES patients in Italy.

The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines produced their first edition in 1999, with subsequent revisions in 2008, 2010, 2016 and 2019. A new iteration of ARIA-ARIA 2024-2025-in collaboration with EAACI is currently being developed, focusing on the management of allergic rhinitis. ARIA 2024-2025 follows the GRADE framework and is endorsed by the European Academy of Allergy and Clinical Immunology (EAACI). A set of approaches has been used to develop guideline questions, including surveying key opinion leaders and using artificial intelligence (AI)-based tools to analyse web searches on allergic rhinitis and to generate questions. Each prioritised guideline question is assessed through an Evidence-to-Decision (EtD) framework. EtDs support the systematic and transparent formulation of recommendations, comprising 12 criteria for which the best available evidence should be sought. In the context of ARIA-EAACI 2024-2025, such evidence is derived not only from randomised controlled trials but also-among others-from patient-generated data sources that better reflect the affected individuals' perspectives. Moreover, ARIA-EAACI 2024-2025 incorporates evidence on planetary health. Developed guideline recommendations will support the creation of digitalised decision algorithms and care pathways. This paper describes the methodology used to develop the person-centred, digitally enabled and AI-assisted ARIA-EAACI 2024-2025. Among others, it describes (i) the development and prioritisation of guideline questions, (ii) sources of evidence for EtDs and (iii) the development of digitalised decision algorithms and care pathways.

Background In the past three years, COVID-19 has had a significant impact on the healthcare systems and people’s safety worldwide. Mass vaccinations dramatically improved the health and economic damage caused by SARS-CoV-2. However, the safety of COVID-19 vaccines in patients at high risk of allergic reactions still has many unmet needs that should be clarified. Material and methods A retrospective, single-centre study was performed by collecting demographic and clinical data of patients with Mast Cell Disorders (MCDs) to evaluate the safety and tolerability of COVID-19 vaccinations. Moreover, any changes in the natural history of the underlying disease following the vaccine have been evaluated. Results This study included 66 patients affected with MCDs. Out of them, 52 (78.8%) received a COVID-19 vaccination and 41 (78.8%) completed the vaccination course. Premedication came first in 86.6% of our patients. A total of seven (4.5%) patients complained about an immediate reaction and two (1.3%) had a late reaction. Worsening of MCD history was observed in a single patient. Conclusions Despite the overall high risk of allergic reactions, our study did not reveal any increased risk for SARS-CoV-2 allergic reactions in MCD patients, thus supporting the recommendation in favour of the SARS-CoV-2 vaccination. However, due to the potentially increased rate of anaphylactic reactions, MCD patients should receive vaccine premedication and should be treated in a hospital setting after an allergological specialistic evaluation.

Alpha‐gal syndrome (AGS) is a mammalian meat allergy associated with tick bites and specific IgE to the oligosaccharide galactose‐α‐1,3‐galactose (α‐gal). Recent studies have shown that 10–20% of AGS patients also react to the dairy proteins. Considering the already described role of the meat lipid fraction in AGS manifestations, the aim of this work has been to investigate whether the milk fat globule proteins (MFGPs) could be involved in AGS.The MFGPs are extracted and their recognition by the IgE of AGS patients is proved through immunoblotting experiments. The identification of the immunoreactive proteins by LC‐HRMS analysis allows to demonstrate for the first time that butyrophillin, lactadherin, and xanthine oxidase (XO) are α‐gal glycosylated. The role of xanthine oxidase seems to be prevalent since it is highly recognized by both the anti‐α‐gal antibody and AGS patient sera.The results obtained in this study provide novel insights in the characterization of α‐Gal carrying glycoproteins in bovine milk, supporting the possibility that milk, especially in its whole form, may give reactions in AGS patients. Although additional factors are probably associated with the clinical manifestations, the avoidance of milk and milk products should be considered in individuals with AGS showing symptoms related to milk consumption.

ObjectiveThe anti-COVID vaccination campaign has led to a significant increase in the demand for allergology consultations in patients considered at risk of reaction to anti-COVID-19 vaccines. This study aims to describe the experience of the vaccination campaign held in Piedmont (Italy) which developed a new service of Allergy Call Center (ACC) thus providing for the screening and management of allergy high-risk patients during pandemic.Study DesignA retrospective analysis was performed on all patients considered at high risk for the development of allergic reactions who were referred by the Immunology and Allergy Unit of Azienda Ospedaliera Ordine Mauriziano in Turin, Italy, between December 2020 and December 2022 and also on ACC consultations.MethodsDuring the COVID-19 pandemic, Piedmont Region instituted the ACC, active from May 10th, 2021 to December 31st 2022, to allow vaccinating doctors to require a telephonic consultation for patients who were considered at high risk for the development of allergic reactions. If further diagnostic evaluations were required, the ACC scheduled a visit with a Consultant of the Unit to better assess the clinical situation of the patient. Furthermore, patients referred by General Practitioners, Occupational Doctors and other consultants were also evaluated by the Unit when required.ResultsDuring the operational period the ACC received a total of 15,865 calls and referred only 336 patients to the unit (27.4% of the total referrals), while General Practitioners referred 499 patients (40.8%), Occupational Doctors referred 61 patients (4.9%), and other consultants referred 326 patients (26.6%).ConclusionsEvaluation and management of a large volume of requests seemed to be facilitated by a proactive framework for screening patients at high risk for allergic reactions as the ones referred by our ACC. This approach led to a prominent decrease in allergological visits to our tertiary care Centre, reducing the waiting times and providing additional support for both patients and healthcare providers, thus allowing the vaccinations to be more easily handled.

Asthma continues to be a disease for which there is no cure, even if it can be very well controlled with the appropriate therapies, which take into account the specific phenotype. The paradox of asthma is that asthma can heal spontaneously, albeit in a small percentage of cases. This observation is highly relevant, since understanding the mechanisms of spontaneous healing can pave the way for new strategies for treating asthma. It is likely that the lack of cure for asthma is due to the fact that current therapies target downstream mediators of the inflammatory response. Asthma can be considered a response of maladaptation of the airway epithelium to the environment, through the orientation of the innate immunity towards an inflammatory response. The important effect of the environment on asthma progress comes from interventions which help children who live in disadvantaged urban neighborhoods move to higher resourced neighborhoods. It is quite interesting that the magnitude of decrease of exacerbations associated with moving was larger than the effect of inhaled corticosteroids and similar to that observed for the effect of biologic agents. Alpine altitude climate treatment is a natural treatment that targets biological pathway, improving various outcomes such as asthma control and quality of life, exacerbation rate and hospitalizations. If as researchers we want to set ourselves the goal of achieving complete remission of asthma, without the need for ongoing maintenance treatment, we need to change the approach to finding new asthma treatment strategies. The One Health approach, an interdisciplinary strategy with focal point on human, animal, and environmental health interconnections, appears to be the right tool for researching asthma prevention and treatment.

INTRODUCTION:Inborn errors of immunity (IEI) represent a heterogeneous group of diseases in which the true prevalence of GI involvement is not well-known. This study evaluates the prevalence of lower GI manifestations in patients with common variable immunodeficiency (CVID), analysing the histologic findings in colonic samples and assessing any correlations with biochemical abnormalities.MATERIALS AND METHODS:A retrospective study was performed by collecting the data of IEI adult patients followed up at two main Northern Italian centres. Demographic and clinical data, and blood tests were collected. A colonoscopy with multiple biopsies in standard sites, in addition to a biopsy for any macroscopic lesion, was performed. The gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) and the short Inflammatory Bowel Disease Questionnaire (sIBDQ) were used to assess GI symptoms.RESULTS:141 patients were included: 121 (86.5%) with CVID, 17 (12.1%) with IgG subclass deficiency, and 2 (1.4%) with X-linked agammaglobulinemia. Of the patients, 72 (51%) complained of GI symptoms. No differences were seen between patients receiving or not IgRT. GI infections were found in 9 patients (6.4%). No significant correlations were found between gut infections and symptoms or leukocyte infiltrates. Colonoscopy alterations were present in 79 patients (56%), and the most common were colon polyps (42%). Microscopical abnormalities were seen in 60 histologic samples (42.5%) and the most frequent was nodular lymphoid hyperplasia (40%). A leukocyte infiltrate was present in 67 samples (47.5%), and the most common was a lymphocyte infiltrate (33%). No correlation was found between GI symptoms and macroscopic alterations, whereas a positive correlation between symptoms and microscopic alterations was detected.CONCLUSIONS:GI symptoms and microscopic alterations in colon samples are closely related; hence, it is important to carry out serial colonic biopsies in every CVID patient, even in the absence of macroscopic lesions.