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Background: Severe eosinophilic asthma is frequently associated to chronic rhinosinusitis and nasal polyposis (CRSwNP) that contribute to poor asthma control. Mepolizumab is an anti-IL-5 monoclonal antibody, approved for the treatment of severe eosinophilic asthma. A limited number of studies have assessed the efficacy of mepolizumab on CRSwNP in severe asthmatics. We aim to evaluate the efficacy of mepolizumab on sino-nasal symptoms, polyp growth and asthma control in severe eosinophilic asthma patients with CRSwNP in real life. Methods: In this study 44 severe eosinophilic asthma patients with CRSwNP were treated with mepolizumab (100 mg q4w) for 1 year. The following outcomes were assessed before (T0), after 6 (T6) and 12 months (T12) of treatment: sino/nasal outcome test (SNOT-22), Total Endoscopic Nasal Polyp Score (TENPS), %FEV1 (FEV1/FEV1 predicted) and Asthma control test (ACT). Blood eosinophil count, exhaled nitric oxide (FENO) and prednisone intake were measured. In a subgroup of patients, nasal cytology was performed before (T0), after 6 (T6) and after 12 months (T12) of treatment with mepolizumab. Results: We reported a significant reduction of SNOT-22 [from 51.5 ± 21.2 at baseline (T0) to 31.70 ± 17.36 at T6 and 29.7 ± 21.5 at T12 (T0–T12 p < 0.001)] and a decrease of TENPS (from 2.88 ± 3.07 to 1.70 ± 2.37 and 1.77 ± 2.56 at T0, T6 and T12, respectively, T0–T12 p = 0.99). A significant improvement of %FEV1, ACT and a decrease in blood eosinophils and mean prednisone intake were also reported. No statistically significant decreasing trend was measured for FENO. Nasal cytology findings suggest a significant reduction of eosinophil percentage following mepolizumab treatment (from 16.8 ± 7.2% to 3.6 ± 6.2% and 0.8 ± 2.4% at T0, T6 and T12 respectively, T0 to T12: p < 0.001). Conclusions: Mepolizumab improves sino-nasal and asthma symptoms and reduces polyp growth in patients with severe eosinophilic asthma and concomitant CRSwNP in real life. The reviews of this paper are available via the supplemental material section.

Nitric oxide (NO) is a short-lived gas molecule which has been studied for its role as a signaling molecule in the vasculature and later, in a broader view, as a cellular messenger in many other biological processes such as immunity and inflammation, cell survival, apoptosis, and aging. Fractional exhaled nitric oxide (FeNO) is a convenient, easy-to-obtain, and non-invasive method for assessing active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid the diagnosis and monitoring of several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory and/or immunological conditions, including allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, atopic dermatitis, eosinophilic esophagitis, and food allergy. In this review, we aim to provide an extensive overview of the current state of knowledge about FeNO as a biomarker in type 2 inflammation, outlining past and recent data on the application of its measurement in patients affected by a broad variety of atopic/allergic disorders.

Clinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria. We enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV ≥ 80% after 1 year of biologic treatment were classified as in clinical remission. 30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV % between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement. anti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, small vessel, necrotizing vasculitis. The disease is mainly characterized by hypereosinophilia and asthma with frequent sinonasal involvement, although multiple organs can be affected, including the heart, lungs, skin, gastrointestinal tract, kidneys, and nervous system. IL-5 production is pathogenetically central for the development of the disease by promoting proliferation, transvascular migration and functional activation of eosinophils. The degree of blood and tissue eosinophilia appears to be associated with disease pathogenesis and eosinophil depletion represents a promising treatment approach for EGPA. We prospectively evaluated the efficacy and safety of a low dose (100 mg q4w), 12-month course of mepolizumab, an anti-IL-5 monoclonal antibody, in eight patients with severe asthma and active EGPA. Patients were recruited by the tertiary care center of Clinical Immunology and Allergy, University of Naples Federico II. The following outcomes were assessed before (T0), and after 6 (T6) and 12 months (T12) of mepolizumab treatment: Birmingham Vasculitis Activity Score (BVAS), prednisone intake, Sino-Nasal Outcome Test (SNOT-22), Total Endoscopic Polyp Score (TENPS), Asthma Control Test (ACT), Forced Expiratory Volume one second (FEV1)%, blood eosinophilia. BVAS score significantly decreased showing a sharp reduction in disease activity score. Clinical improvements in terms of sinonasal scores and asthma symptoms were observed, in parallel with a drastic drop in eosinophil blood count. Prednisone intake was significantly reduced. In two patients, asthma exacerbations led to discontinuation in mepolizumab therapy after 6 and 12 months despite BVAS reduction. Mepolizumab treatment was well tolerated, and no severe adverse drug effects were registered. In conclusion, our 12-month real-life study suggests that mepolizumab may be beneficial and safe in active EGPA patients by improving disease activity score, sinonasal and asthma outcomes while reducing the burden of prednisone intake.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia. To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months. We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed. 49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all 0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab ( 0.0001), while benralizumab depleted both eosinophils ( 0.0001) and basophils ( <0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients. These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.

Chronic rhinitis (CR) is commonly divided into allergic rhinitis (AR) and nonallergic rhinitis (NAR). AR is triggered by the immunoglobulin E (IgE)-mediated response to allergens, whereas NAR is characterized by the absence of allergic sensitization. Previous studies have demonstrated the presence of local IgE in the nasal mucosa of patients suffering from typical allergic rhinitis (AR) symptoms but without a history of atopy and a positive response to a nasal allergen challenge (NAC). This condition was recently defined as local allergic rhinitis (LAR), which is supposed to be a different CR characterized by a type 2 (T2) inflammation response with the release of typical T2 mediators. LAR is defined as a phenotype of AR characterized by a localized nasal allergic response that is negative skin prick testing to allergens in the absence of serum-specific IgE. Diagnosis is based on a positive response to NAC. This review is an update of LAR literature, focusing on the definition of LAR as an independent endotype. LAR, AR, and NAR are characterized by the same clinical symptoms, although there are some differences between these three subtypes. However, the literature data are not yet univocal in defining LAR as an independent endotype.

Background/Objectives: Eosinophilic esophagitis (EoE) is a T2-mediated disease characterized by dysphagia and food impaction. It is often associated with other atopic disorders and is considered a late manifestation of the “atopic march”. In clinical practice, allergic comorbidities are frequently underdiagnosed and primarily based on self-reporting, potentially underestimating the true burden of T2-related pathology. To address this, a multidisciplinary task force was established at our tertiary center to systematically evaluate newly diagnosed patients with EoE. Methods: This cross-sectional observational study included patients referred for EoE evaluation from January 2022. Clinical history was collected prospectively, with systematic assessment for T2 comorbidities. All patients underwent an esophagogastroduodenoscopy with esophageal biopsies. Following EoE diagnosis, patients were referred to dermatology, ENT, immunology, and respiratory specialists. Results: A total of 43 patients were enrolled. Anamnestic T2 comorbidities were reported by 88% of patients. Rhinitis was the most common, while at baseline, no patients reported chronic rhinosinusitis with nasal polyps (CRSwNP). After specialist evaluation, diagnoses of asthma, food allergy, and atopic dermatitis remained stable, while eight patients previously reporting rhinitis were newly diagnosed with CRSwNP. Overall, 65% of patients had ≥2 T2 comorbidities in addition to EoE, and 25% had ≥3. Conclusions: Our findings support a multidisciplinary approach to assess T2 comorbidities in patients with EoE, with a high overall prevalence (95.3%) and frequent coexistence of multiple atopic conditions. CRSwNP was frequently underdiagnosed and only identified after rhinofibroscopy. Although our data needs to be confirmed in larger multicenter studies, our results suggest that relying solely on patient-reported history or single-specialty evaluation risks underestimating the systemic nature of the T2 inflammatory pathway in EoE.

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

Idiopathic hypereosinophilic syndrome currently represents a major unmet need for all medical specialties dealing with this disease. Markers capable of characterising the wide variability of its clinical presentation are currently lacking. This study aims to evaluate a panel of possible markers in idiopathic hypereosinophilic syndrome. In this pilot prospective single-centre cohort study, we analysed clinical (age, years of disease, steroid therapy) and laboratory (absolute eosinophil count, total IgE antibodies, IgE antibodies against Staphylococcus aureus enterotoxins, serum eosinophil cationic protein, serum immunoglobulin free light chains k and λ and their ratio) data obtained from 21 patients suffering from idiopathic hypereosinophilic syndrome from June 2023 to December 2024. Mean absolute eosinophilic count was 3758.57 cells/μL. 17 patients were receiving treatment with > 7.5 mg of prednisone or equivalent at the time of the diagnosis. 13 patients had positive Staphylococcus aureus enterotoxins IgE, while the mean total serum IgE was 241.64 kU/L. We observed a high serum eosinophil cationic protein value as well as a high serum κ free light chain, while serum λ and κ/λ were normal. Patients with higher absolute eosinophilic count had higher eosinophil cationic protein levels ( < 0.05), such as higher steroid consumption ( < 0.05). In addition, we found a strong association between high κ free light chain levels and high previous steroid use and with Staphylococcus aureus enterotoxins IgE positivity. Our results could increase the number of possible biomarkers for risk stratification in idiopathic hypereosinophilic syndrome.

A specific predictive tool of allergen immunotherapy (AIT) outcome has not been identified yet. This study aims to evaluate the efficacy of a disease score referred to as Predictive Response to Immunotherapy Score (PRIS) to predict the response to AIT and identify eligible patients. A total of 110 patients diagnosed with allergic rhinitis with or without concomitant asthma were enrolled in this study. Before beginning sublingual immunotherapy (SLIT), patients were evaluated by analyzing clinical and laboratory parameters. A specific rating was assigned to each parameter to be combined in a total score named PRIS. At baseline (T0) and follow-up [after 12 (T12) and 24 months (T24) of SLIT], a Visual Analogue Scale (VAS) was used to calculate a mean symptom score (MSS). Finally, the percentage variation between the MSS at T0 and at T12 [ΔMSS-12(%)] and T24 [ΔMSS-24 (%)] was measured. We observed a significant improvement of symptoms at T12 and T24 compared to T0 in all groups undergoing SLIT. PRIS was effective in predicting ΔMSS-24 (%) in patients treated with single-allergen SLIT. In addition, PRIS was effective in predicting ΔMSS-24 (%) in both patients with only rhinitis and with concomitant asthma. PRIS assessment can represent a useful tool to individuate potential responders before SLIT prescription.