Background: Long COVID remains a challenging and heterogeneous condition, with mechanisms that are still incompletely understood. Emerging evidence suggests that patients with allergic disease may experience more persistent post-COVID symptoms, possibly due to immune dysregulation and epithelial barrier fragility. Methods: We carried out an observational, single-center study at the Allergy and Clinical Immunology Unit of Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). Seventeen adults with confirmed allergic disease and long COVID were evaluated between July and December 2024. Biomarkers reflecting allergic inflammation and barrier integrity, blood eosinophil count, total immunoglobulin E (IgE), eosinophil cationic protein (ECP), and serum free light chains (FLCs), were measured and analyzed for interrelationships and symptom correlations. Results: Participants (10 men, 7 women; mean age 43.7 years) showed variable biomarker profiles, consistent with the heterogeneity of allergic inflammation. Mean eosinophil count was 179 ± 72 cells/µL, total IgE 165.4 ± 140.6 kU/L, ECP 64.2 ± 48.5 ng/mL, and the kappa/lambda FLC ratio 1.20 ± 0.69. Notably, elevated kappa FLC levels (>19.4 mg/L) were significantly associated with high ECP (>20 ng/mL) (χ2 = 10.6, p = 0.001) and increased IgE (>200 kU/L) (χ2 = 6.0, p = 0.015). Individuals with higher ECP and FLCs more often reported respiratory and systemic symptoms, especially fatigue, dyspnea, and cognitive fog, that persisted beyond six months. Conclusions: These findings suggest that biomarkers of allergic inflammation and barrier dysfunction, particularly ECP and FLCs, may contribute to the persistence of long-COVID symptoms in allergic patients. The observed links between humoral activation, eosinophilic activity, and prolonged symptom burden support a model of sustained inflammation and delayed epithelial recovery. Larger, longitudinal studies including non-allergic controls are warranted to confirm these associations and to explore whether restoring barrier integrity could shorten recovery trajectories in this vulnerable population.

Background: Urticaria, particularly chronic urticaria (CU), is a highly prevalent inflammatory skin disorder characterized by recurrent wheals and/or angioedema with a fluctuating and unpredictable course that significantly impairs quality of life and requires long-term monitoring. Despite established therapeutic guidelines, disease control remains suboptimal in a considerable proportion of patients. Telemedicine has emerged as a promising adjunctive strategy for chronic disease management. This review aims to critically evaluate the role, applications, benefits, and limitations of telemedicine and digital health interventions in urticaria management. Methods: A scoping review of the literature was conducted focusing on studies addressing telemedicine, digital patient-reported outcomes, mobile health applications, and remote monitoring strategies in urticaria. Evidence from pandemic and post-pandemic telemedicine models was also analyzed to identify transferable approaches. Results: Telemedicine demonstrates significant potential in urticaria management by enabling structured symptom monitoring, facilitating remote follow-up during therapeutic escalation (including biologic therapies), improving patient empowerment and adherence, and reducing healthcare utilization and indirect costs. Digital tools such as electronic diaries and validated PRO-based applications support continuous disease assessment. However, telemedicine cannot replace direct clinical examination, and limitations include diagnostic uncertainty, digital inequalities, data privacy concerns, and lack of large disease specific trials. Conclusions: Telemedicine represents a valuable complementary and integrative model for urticaria care, particularly suited for chronic disease monitoring. Hybrid care pathways combining remote and in-person management appear to be the most effective and sustainable strategy. Further high-quality urticaria-specific studies and standardized digital frameworks are required to optimize its clinical implementation.

Background: Clinical remission is an emerging treatment goal in severe eosinophilic asthma (SEA). While benralizumab, an anti-IL-5Rα monoclonal antibody, has demonstrated efficacy in SEA, its ability to induce clinical remission in real-life settings over extended follow-up remains underexplored. Methods: This post hoc analysis of the multicenter, retrospective ANANKE study evaluated clinical remission over 24 months in 167 Italian patients with SEA treated with benralizumab. Remission was defined according to the Severe Asthma Network Italy (SANI) criteria. Complete clinical remission (cCR) required the absence of oral corticosteroid (OCS) use and the presence of 3 criteria: no symptoms, no exacerbations, and stable lung function. Partial clinical remission (pCR) required the absence of OCS use and 2 of the 3 criteria. Outcomes were assessed at 3, 12, and 24 months. Results: The proportion of patients achieving clinical remission increased over time: 87.2% at 3 months (40.4% pCR, 46.8% cCR), 95.0% at 12 months (17.5% pCR, 77.5% cCR), and 96.1% at 24 months (23.5% pCR, 72.6% cCR). No baseline demographic or clinical characteristics were found to significantly predict remission status. Blood eosinophil counts declined from a mean of 476.7 to 5.2 cells/μL at 24 months. Conclusion: In this real-world Italian cohort, benralizumab was associated with rapid and sustained clinical remission in patients with SEA over 24 months. The high remission rates observed early and maintained throughout treatment support the role of benralizumab as a disease-modifying therapy and reinforce clinical remission as a meaningful therapeutic goal in SEA.

Atopic dermatitis (AD) is a common inflammatory skin disorder which presents with recurrent eczematous lesions and itching. Its pathophysiology is complex and multifactorial. Alterations in cell-mediated immune responses, barrier dysfunction, environmental aspects and IgE-mediated hypersensitivity are all involved. This review aims to provide the clinician with an update on the impact that Th2 inflammation can have on growth and osteoimmunology. The potential adverse or protective effects brought on by the many therapies administered in this condition are also considered. Moreover, through this analysis, we aim to show how, by inhibiting the IL-4 and IL-13 signaling pathways—fundamental in the T helper 2 (Th2) immune axis and in AD pathogenesis—dupilumab may exert a protective role on growth and osteoimmunology in moderate-to-severe AD, particularly in young patients. This focus is essential for the correct, safe management of patients with Th2 inflammation.

Background:Clinical remission is increasingly recognized as a primary treatment goal in severe asthma, particularly severe eosinophilic asthma (SEA), where comorbidities such as chronic rhinosinusitis with nasal polyps (CRSwNP) contribute to persistent inflammation and treatment burden. Benralizumab, an anti-IL-5Rα monoclonal antibody, has shown efficacy in achieving sustained control in SEA, but long-term real-world data beyond 36 months remain limited. Objective:To evaluate the long-term (48-month) effectiveness of benralizumab in SEA patients, focusing on clinical remission, airway function, and reduction of background therapy, including oral corticosteroids (OCS) and inhaled corticosteroids (ICS). Methods:In this retrospective, multicenter study across 9 Italian centers, 128 adult SEA patients (mean age 57.1 years, 57% female; 59.4% with CRSwNP) were treated with subcutaneous benralizumab for up to 48 months. Clinical remission was assessed using SANI criteria: partial (pCR, meeting ≥2 of 3 criteria without OCS) and complete (cCR, all criteria fulfilled without OCS). Outcomes included annualized exacerbation rate (AER), pulmonary function (FEV1, FEV1/FVC, FEF25-75%), airway inflammation (FeNO, blood eosinophils), patient-reported outcomes (ACT, ACQ-6, AQLQ), and background therapy use. Mixed-effects regression models evaluated longitudinal changes. Results:Benralizumab induced rapid and sustained improvements. AER decreased from 3.62 to 0.33 at 48 months; blood eosinophils were nearly undetectable throughout. FEV1 increased from 2.04 L to 2.49 L, with proportional gains in FEV1/FVC and FEF25-75%. ACT and ACQ-6 scores improved significantly (p < 0.001), and sinonasal symptoms in CRSwNP patients declined (VAS 4.70 → 2.31). OCS discontinuation was achieved in 88.5% of patients at 48 months, with mean ICS dose reduced by 35%. Overall, clinical remission was observed in 87.9% of patients, with cCR in 63.8%. Improvements were consistent regardless of ICS dose reduction. Conclusions:Long-term benralizumab treatment in SEA patients leads to rapid, sustained clinical remission, improved large and small airway function, and significant reduction of background therapy, including OCS and ICS. These results support the role of benralizumab as a disease-modifying therapy and highlight the feasibility of remission-based management in real-world practice.

Background: Precision medicine targets clinical remission, but traditional symptom-based frameworks often ignore the biological pathways driving the disease. Adequate T2 biomarker interpretation is crucial to identify phenotypes where FeNO reflects epithelial barrier distress. We investigated the “clinical-biological gap” through the analysis of six groups to distinguish profiles of symptomatic resilience from biological insensitivity to corticosteroids. Methods: Real-world study of 292 patients stratified into six groups based on BEC (≥250 cells/microL), FeNO (≥25 ppb), and IgE (≥100 kU/L). ACT, BMI, FEV1, comorbidities, and therapeutic burden were analyzed. Results: The EoS+ IgE+ group showed “symptomatic resilience”: apparent clinical control (54.5% ACT ≥ 20) supported by a critical pharmacological burden (90% salbutamol, 80% OCS ≥ 7.5 mg). The Triple Positive and EoS+ FeNO+ groups depicted “Maximum Steroid Insensitivity,” characterized by poor control despite maximal ICS/OCS regimens. FeNO could appear like the primary driver of instability, reflecting a trajectory of oxidative stress not altered by steroids. Conclusions: T2 biomarkers provide a unique prognostic value unidentifiable by standard clinical assessment. FeNO monitoring unmasks silent distress in resilient patients and identifies the “therapeutic wall” in refractory profiles. Therefore biological remission could represents the only effective target to modify the natural history of the disease.

To review current evidence on biologic therapies targeting type 2 inflammation in patients with eosinophilic COPD and respiratory comorbidities who remain uncontrolled despite optimized triple inhaled therapy. Recent phase 3 trials have shown that dupilumab provides the most consistent benefit in eosinophilic COPD, reducing exacerbations and improving lung function and quality of life. Mepolizumab has shown a more limited effect, mainly on exacerbation reduction, whereas benralizumab has not demonstrated clear clinical benefit. Blood eosinophil count remains the main biomarker for treatment selection. Biologic therapies are advancing precision medicine in COPD, with dupilumab currently showing the strongest overall evidence. Careful patient selection is essential. Broader phenotyping may further improve management, as comorbidities such as chronic rhinosinusitis may contribute to symptom burden and support a multidisciplinary approach. Future studies should clarify long-term outcomes and optimal biologic selection.

Eosinophilic esophagitis (EoE) first-line therapy is represented by budesonide orodispersible tablets (BOT), but a very low number of patients develop oral and esophageal candidiasis. The aim of the study is to evaluate risk factors for the development of oral and esophageal candidiasis during budesonide therapy in EoE patients. A retrospective study was conducted to include all EoE patients in BOT therapy referred to our center. Prevalence, localization, and time of presentation of candidiasis, eosinophilic count in gastroscopy before BOT therapy, and concomitant treatment with proton pump inhibitors (PPI) and its dosage were reviewed. A total of 46 EoE patients in BOT therapy were included in the study. 7 patients (15

Purpose:Speed of clinical response to a new therapeutic intervention is a critical determinant of the overall treatment outcomes, but tools focused on asthma response speed are currently unavailable. This study aimed to validate the psychometric properties of a new questionnaire initially written in Italian, the Speed of Change in Feeling of Health (SCFH), in patients with asthma. Patients and Methods:Two hundred and seventy subjects with not-well- or poorly controlled asthma, enrolled in the Italian sites of the NEWTON real-world study, were asked to complete the provisional version of SCFH and three validated questionnaires, the Stanford Expectation of Treatment Scale (SETS), the 5-item version of the Asthma Control Questionnaire (ACQ-5), and the Global Rating Scale (GRS). Internal consistency and validity were determined. Moreover, we assessed the minimal clinically important difference (MCID) using anchor-based method. Results:One hundred and ninety-six patients completed the questionnaire at least once at 7 (±1), 14 (±2), or 30 (±3) days after starting BDP/FF NEXThaler® 100/6 μg treatment. We started from SCFH provisional questionnaire of 30 items, the internal consistency of which revealed a high redundancy (Cronbach's alpha of 0.98), prompting its reduction to an 8-item questionnaire (SCFH-8; Cronbach's alpha = 0.90). Known-group validity indicated significant differences in SCFH-8 scores (p = 0.0003) at 30 (±3) days after enrollment between improved and non-improved subjects, as defined by changes in ACQ-5 scores. The study confirmed the convergent validity through comparisons with the SETS and the ACQ-5 questionnaires. A clinically relevant change in feeling of health was observed in 43.3% of participants at 7 days, while the cumulative frequency of patients reporting a clinically relevant change in their feeling of health at 30 days after enrollment was 70.4%. Conclusion:The Italian version of SCFH-8 is a valid, short tool with good psychometric properties for determining the speed of change in health perception after starting treatment.

BACKGROUND:Asthma is a common chronic disease worldwide, with most patients presenting with mild to moderate forms. Poor adherence to inhaled therapy is a recognized determinant of worse outcomes in chronic respiratory diseases. The aim of this study was to evaluate adherence to inhaled medications in a large cohort of adults with mild to moderate asthma and identify factors associated with suboptimal adherence. METHODS:This cross-sectional real-world study analyzed data from the Mild-Moderate Asthma Network of Italy (MANI) database. Adult patients (≥18 years) with a confirmed diagnosis of asthma according to Global Initiative for Asthma (GINA) criteria were eligible. Data from the first visit in which the Test of Adherence to Inhalers (TAI) questionnaire was available were extracted. Patient-reported outcomes included the Asthma Control Test (ACT), the Asthma Quality of Life Questionnaire (AQLQ), and TAI adherence categories. Patients were classified into three classes according to TAI score as follows: adherents (score ≥50), intermediate adherents (score 46-49), and non-adherents (score <46). RESULTS:A total of 832 patients were included. Adherent patients were older than intermediate and non-adherent subjects (p < 0.001). Current smoking was less frequent among adherent patients (11% vs 16%). Type 2 diabetes and anxiety were more prevalent among non-adherent individuals (5.3% vs 0.8% and 1.8%, p = 0.014; 10.7% vs 7.1% and 3.8%, p = 0.003, respectively). Higher adherence levels were associated with better asthma control (χ2 (2) = 47.706, p < 0.001) and quality of life (χ2 (2) = 42.068, p < 0.001). CONCLUSION:In adults with mild to moderate asthma, better adherence to inhaled therapy is associated with improved disease control and quality of life. Demographic factors, smoking status, and comorbidities may influence adherence behaviors. Routine assessment of adherence and targeted interventions addressing modifiable barriers may improve outcomes in this large asthma population.

Staphylococcus aureus frequently colonizes the skin and upper airways and produces a broad repertoire of immunomodulatory molecules. In asthma, the most consistent evidence concerns staphylococcal enterotoxins (SEs), which can act both as superantigens and as allergens, and IgE sensitization to SEs (SE-sIgE). SE-sIgE is associated with severe asthma, type 2 inflammation, chronic rhinosinusitis with nasal polyps (CRSwNP), exacerbations, and, in some longitudinal studies, persistent airflow obstruction. However, this relationship is not necessarily causal: SE-sIgE may reflect exposure, an immune response, or a biologically active endotype, whereas colonization, local toxin production, and systemic sensitization are not equivalent. SEs simultaneously bind class II MHC molecules and Vbeta regions of the T-cell receptor, activating large fractions of T lymphocytes; they also promote IL-4, IL-5, and IL-13 production, polyclonal B-cell activation, local IgE synthesis, mast-cell degranulation, eosinophilia, and IL-8/neutrophil circuits. Alpha-toxin (Hla) and SEB can damage the epithelial barrier, facilitating allergen penetration and alarmin signalling. These observations support an interaction model in which dysbiosis, barrier dysfunction, and type 2 immunity mutually reinforce one another along the nasobronchial axis. Corticosteroids and antibiotics may modify selected nodes in this circuit, but current evidence is insufficient to recommend decolonization or antitoxin therapy in stable asthma. Biologics interrupt downstream pathways potentially fuelled by toxins: omalizumab neutralizes free IgE; mepolizumab and benralizumab reduce the eosinophilic axis; dupilumab blocks IL-4/IL-13 signalling; and tezepelumab acts upstream on TSLP. Nevertheless, randomized trials stratified by SE-sIgE are lacking, and no evidence demonstrates that these treatments eliminate colonization or toxin production. SE-sIgE therefore appears to be a promising biomarker, particularly in severe asthma with CRSwNP, but it is not yet an autonomous criterion for biologic selection. A broader barrier-organ analysis also identifies nasal, cutaneous, and intestinal colonization as distinct ecological states; atopic dermatitis as a complementary model of toxin-amplified type 2 inflammation; and biofilms and extracellular vesicles as candidate mechanisms of persistent toxin delivery. These data increase biological plausibility but remain indirect for asthma.

Benralizumab improves outcomes in severe eosinophilic asthma patients regardless of smoking history, with former smokers achieving similar benefits in exacerbation reduction, oral corticosteroid sparing, asthma control and lung function to never-smokers https://bit.ly/4grFy7e.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis with heterogeneous clinical manifestations. Identifying reliable biomarkers is crucial to predicting disease evolution and guiding therapy. We analyzed clinical, biological, and functional data from 33 patients with EGPA in the vasculitic phase. Blood eosinophil count (BEC), eosinophilic cationic protein (ECP), antineutrophil cytoplasmic antibodies (ANCAs), specific IgE to staphylococcal enterotoxins (SE-IgE), and serum free light chains (FLCs) were evaluated. Severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNPs) were present in 100% and 88.5% of patients, respectively. Median BEC was 1950 cells/mm3, with elevated ECP (60.0 µg/L). SE-IgE was detected in 54.2% of patients. A significant negative correlation emerged between λ FLCs and oral corticosteroid (OCS) dose (r = –0.58, p = 0.009). Forced expiratory volume in 1 second (FEV1) was significantly lower in C-ANCA+ patients (p = 0.006). ECP and SE-IgE may serve as markers of eosinophilic activity and epithelial barrier damage in EGPA. λ FLCs might be a useful indicator of OCS exposure and treatment response. These biomarkers could support the evaluation of disease evolution and treatment response.

IntroductionAsthma is often treated with oral corticosteroids (OCS), despite their association with significant adverse effects. While guidelines recommend minimizing OCS use through alternative therapies and patient-centered approaches, discrepancies between recommendations and real-world practices persist. This study evaluates OCS usage patterns and barriers to adherence to asthma treatment guidelines in Italy, using surveys conducted with healthcare professionals (HCPs) and patients.MethodsTwo cross-sectional surveys were administered between January and March 2024 to HCPs and asthma patients. The surveys assessed OCS prescription practices, treatment adherence, patient involvement, adverse event management, and perceptions of OCS use. Descriptive analysis was performed to identify patterns and highlight gaps in current practices.ResultsThe surveys revealed considerable variability in OCS prescribing practices, treatment duration and daily dosages. Over 80% of patients reported using OCS and 18% of HCPs believed that the maximum daily doses of OCS are higher than the guideline-recommended doses. Patients did not feel fully involved in treatment decisions, with over 40% of patients reporting unsatisfactory communication about treatment alternatives or adverse effects. Barriers to optimal care included inadequate access to specialists, inconsistent monitoring protocols, and a lack of multidisciplinary approaches. Both HCPs and patients highlighted the need for clearer definitions of OCS dependency and enhanced tools for tracking treatment adherence.DiscussionThe findings underscore the urgent need for systemic reforms to align clinical practice with guidelines. These include establishing pragmatic definitions for OCS dependency, promoting multidisciplinary care, and leveraging technology for monitoring. Addressing psychosocial factors and empowering patients through education and shared decision-making are also critical.

Background/Objectives: Food protein-induced enterocolitis syndrome (FPIES) is a food-related hypersensitivity disorder characterized by delayed repeated vomiting that typically presents within the first years of life. Although FPIES has traditionally been considered a pediatric condition, it has more recently been observed also in teenagers and adults. Adult FPIES may be a continuation of childhood-onset disease or new-onset forms developing later in life. This review aims to describe the peculiarities of FPIES across the lifespan and to provide an update from the last years on the studies focused on FPIES in adolescence. Methods: Papers focusing on FPIES in adolescents, in English and published in PubMed, were reviewed. Results: There is less data available in the literature on FPIES in adolescents. Multiple sensitizations to food can compromise nutritional status in patients with FPIES. Several potential diagnostic biomarkers related to genomic susceptibility, altered immunologic response, mucosal inflammation and intestinal microbiota are under study/validation. The lack of age-specific diagnostic algorithms makes it difficult to understand the clinical features of persistent forms of FPIES. Conclusions: Shared transition medicine protocols tailored to adolescents could help us better understand the clinical, pathophysiological, diagnostic, and therapeutic characteristics of this delicate phase of life.

Over the past decades, monoclonal antibodies have been playing a pivotal role in the treatment of chronic inflammatory airway diseases. Currently, ample data are available on the efficacy and safety of biologics in asthma from randomized controlled trials and open-label trials; conversely, limited data are available on the use of biologics in chronic obstructive pulmonary disease. In this context, once the fundamental role of inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist therapy is established, clinical response and disease remission, based on clinical and functional response parameters such as oral corticosteroid need, annual exacerbation rates, and lung function, are the key factors driving the clinical and therapeutic management. This narrative review has summarized the literature data from randomized controlled trials and real-life experience on currently available biologics in asthma and chronic obstructive pulmonary disease. The role of inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist therapy has been further investigated with a particular focus on drug-free concept.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder associated with rhinorrhea, nasal obstruction, nasal congestion, hyposmia, anosmia, and facial pain or pressure for over 12 weeks. This study examines the Sino-Nasal Outcome Test 22 (SNOT-22) score and its relationship to nasal, otologyc, sleep and emotional domains in CRSwNP patients during the first year of biologics treatment, comparing the pre-biologics score to that at 1, 6, and 12 months in a cohort of 59 patients with CRSwNP. Methods: We included 59 patients with CRSwNP (with or without asthma) who received add on therapy with targeted monoclonal antibodies (mAbs). At each visit we administered the SNOT-22 questionnaire and both total score and single domains scores were recorded. Results: In this real-life, observational study, we found a significant SNOT-22 total score reduction for patients treated with anti-IgE after 1 month, but this significant difference was not maintained at 6 or 12 months compared with the baseline. The use of anti-interleukin 5/5R (IL5/5R) leads to a significant reduction of the SNOT-22 total score after 1 month, which is maintained after 6 months but not at 12 months compared with the baseline. The use of an anti-interleukin 13/4R (IL13/4R) leads to a statistically significant reduction of the SNOT-22 score after 1 month of therapy, which is maintained after 6 and 12 months compared with the baseline. When examining the single domains, we observed that patients who received anti-IL13/4R treatment demonstrated a significant reduction in each domain at each time point (T) compared to the baseline. Patients who received anti-IL5/5R treatment demonstrated an improvement in the nasal domain at each T compared to the baseline. However, the improvement in the otologyc domain was not sustained after 12 months. Similarly, the sleep domain remained unchanged, and the emotional domain only improved significantly after 12 months. Similarly, there was a reduction of the emotional domain in patients treated with anti-IgE. Conclusion: Our real-life study describes the kinetics over the first year of treatment with mAbs in CRSwNP, showing different patterns in reducing symptoms and improving Health Related Quality of Life (HRQoL). SNOT-22 with the factorial division in 4 domains can help distinguish fast responders from low or non-responders to a mAb based on clinical response after 1 month and more accurately assign the right mAb to the right patient.