PURPOSE:This study aims to assess, for the first time, the efficacy and safety of Tezepelumab in managing ear, nose, and throat manifestations and improving quality of life in asthma patients treated in a real-world setting. Chronic rhinosinusitis is a heterogeneous condition, characterized by various phenotypes that often coexist with comorbidities. While the standard treatment is commonly applied to chronic rhinosinusitis, a significant number of patients do not respond adequately to medical management and experience frequent relapses of nasal polyps. Current biologic therapies primarily target type 2 chronic rhinosinusitis; however, no specific treatments are available for non-type 2 or mixed forms. Tezepelumab, an anti-TSLP monoclonal antibody for severe asthma, emerges as a promising treatment for TSLP-driven diseases. METHODS:We conducted a prospective observational study involving 26 patients with severe asthma who also presented sinonasal symptoms. Clinical assessments included nasal endoscopy, nasal congestion scores, SNOT-22, visual analog scale, nasal airflow measurement, olfactory evaluation, and eosinophil count. All 26 patients completed at least 3 months of follow-up. RESULTS:We observed significant improvements in nasal endoscopy scores, nasal congestion scores, SNOT-22, visual analog scale, and olfactory function. CONCLUSION:These results highlight the potential of Tezepelumab as a versatile therapeutic option for both severe asthma and chronic rhinosinusitis, including phenotypes previously excluded from biologic treatments. However, larger, more homogeneous studies are needed to confirm these findings. We believe that our real-world data may have important implications for the management of chronic rhinosinusitis, regardless of the underlying inflammatory phenotype.

Angelantonio Maglio,1 Carolina Vitale,1 Luisa Oriana D’Auria,1 Valeria Longobardi,1 Antonio Franzese,1 Corrado Pelaia,2 Girolamo Pelaia,2 Cecilia Calabrese,3 Alessandro Vatrella11Department of Medicine, Surgery, and Dentistry "Scuola Medica Salernitana”, University of Salerno, Salerno, Italy; 2Department of Medical and Surgical Sciences, University "Magna Graecia” of Catanzaro, Catanzaro, Italy; 3Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples, ItalyCorrespondence: Alessandro Vatrella, Department of Medicine, Surgery, and Dentistry "Scuola Medica Salernitana”, University of Salerno, Salerno, Italy, Email avatrella@unisa.itAbstract: Severe eosinophilic asthma (SEA) is a type-2 inflammatory phenotype driven by persistent eosinophilia, characterized by frequent exacerbations, progressive lung function decline, and substantial oral corticosteroid (OCS) dependence, for which conventional therapies remain insufficient in a significant minority of patients. Benralizumab—a humanized, afucosylated anti-interleukin-5 receptor alpha (IL-5Rα) monoclonal antibody—achieves near-complete depletion of eosinophils and basophils through dual receptor blockade and afucosylation-enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), producing one of the most extensive anti-eosinophilic effects among currently approved biologics. Pivotal Phase 3 trials (SIROCCO, CALIMA, ZONDA) demonstrated annual exacerbation rate reductions of up to 51%, robust OCS-sparing with complete elimination in 52.7% of OCS-dependent patients, and significant improvements in forced expiratory volume in 1 second (FEV1). Long-term extension data over five years (MELTEMI) confirmed sustained efficacy and safety, without evidence of adverse consequences attributable to chronic eosinophil depletion. Landmark studies including PONENTE, SHAMAL, and ABRA have further extended benralizumab’s clinical impact: enabling structured OCS elimination, demonstrating that well-controlled patients can reduce inhaled corticosteroids to as-needed therapy, and establishing biologic-based treatment of acute eosinophilic exacerbations as a viable new approach. Real-world evidence consistently corroborates trial findings, with clinical remission—defined as the composite achievement of exacerbation freedom, OCS independence, symptom control, and preserved lung function—reported in 17– 44% of patients at 12 months and up to 91% in selected longer-term cohorts. Beyond asthma, benralizumab demonstrates meaningful activity in comorbid chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis, and eosinophilic esophagitis. This review comprehensively examines benralizumab’s molecular pharmacology, pivotal and real-world clinical evidence, comorbidity management, and its central role in driving the paradigm shift from symptom control toward clinical remission in severe eosinophilic airway disease.Keywords: severe eosinophilic asthma, IL-5 receptor alpha, clinical remission, oral corticosteroid sparing, type-2 inflammation, biologic therapy

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.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 variants with variable severity. Current international guidelines do not recommend augmentation therapy for intermediate AATD; nevertheless, some patients show clinically severe phenotypes in real-world practice. We aimed to evaluate, in an exploratory manner, the potential effects of augmentation therapy on exacerbations, quality of life, and lung function in this subgroup. Methods: In this multicenter retrospective study, we included 27 heterozygous patients with intermediate AATD (serum AAT 50–110 mg/dL), Chronic Obstructive Pulmonary Disease (COPD), and/or emphysema. Clinical phenotypes included emphysema-predominant disease, COPD with frequent exacerbations, and overlap with bronchiectasis/asthma; HRCT patterns were recorded. We assessed the annual number of exacerbations (moderate: steroids/antibiotics; severe: hospitalization/including pneumothorax), St. George’s Respiratory Questionnaire (SGRQ), and lung function before and after 12 months of therapy. Results: Augmentation therapy was associated with a reduction in annual exacerbations from a median (IQR) of 2 (1.5–3) to 1 (0–1) (p < 0.0001) and an improvement in SGRQ total score (58.89 ± 16.83 to 48.34 ± 21.20; p = 0.0039). The mean SGRQ change exceeded the 4-point MCID for COPD. No significant changes were observed in spirometry or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO). Conclusions: These exploratory findings suggest that augmentation therapy may reduce exacerbations and improve quality of life in selected patients with intermediate AATD and COPD/emphysema. Given the retrospective design, small sample, and lack of a control group, the results should be interpreted as hypothesis-generating and warrant confirmation in prospective studies.

BACKGROUND: Chest high-resolution computed tomography (HRCT) plays a key role in the diagnosis and follow-up of patients with organizing pneumonia (OP). However, its repeated use is limited by high cost and radiation exposure. The aim of the study was to evaluate the utility of diffusion lung carbon monoxide (DLCO) test in monitoring OP response to oral corticosteroid (OCS) therapy and in relation to HRCT modifications. METHODS: It was a retrospective study. Among 40 OP patients, 20 had complete pulmonary function test and HRCT at baseline (T0) and after 3 months (T3) of OCS therapy and 16 after 6 months (T6). HRCT response to OCS was defined "complete" or "partial" in absence or persistence of any OP radiological findings, respectively. RESULTS: In comparison with T0, at T3 both DLCO and forced vital capacity (FVC), percentage (%) and absolute values, significantly increased (P<0.001, P<0.001, P=0.015, P=0.028, respectively), while at T6 in comparison with T3, only DLCO, % and absolute values, significantly increased (P=0.0007, P=0.02, respectively).At T3, 10 patients showed a complete and 10 a partial radiological response. Comparing the two groups of patients, although at T0 there was no significant difference in pulmonary functional test (PFT) parameters, the complete radiological response group showed significantly higher % DLCO values in comparison with the partial response group (P=0.03). No significant difference in FVC was observed. CONCLUSIONS: DLCO is a safe test that resembles HRCT modifications and can be used in the follow-up of patients affected by OP.

INTRODUCTION:Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that subverts the normal structure of the lungs and finally causes respiratory failure. High-flow nasal therapy (HFNT) is currently used in the acute setting for IPF with acute respiratory failure. Also, acute exacerbation of IPF and end-stage disease are common indications. Chronic cough is often an unmet need in IPF because it is partially responsive to common pharmacological treatment. Moreover, opioids have known adverse events. The aim of this paper was to investigate the effects and safety of chronic HFNT on lung function and symptoms of IPF. METHODS:This is a single-center case-control study including patients affected by IPF. We included 35 adult patients with a consistent radiological diagnosis of IPF, clinical history of lung function decline, and high prevalence of symptoms. All patients received the standard of treatment, particularly including antifibrotic drugs and conventional oxygen therapy (COT). Eighteen subjects were assigned to additional treatment with HFNT for 12 months. RESULTS:No significant differences were observed after the follow-up with HFNT in terms of lung function. The mean forced vital capacity (FVC) was 1.89 ± 0.73 L with HFNT and 2.43 ± 0.87 L without HFNT (p = 0.09). The mean FVC decline per year was 190 mL with HFNT versus 200 mL with standard of care. The mean DLCO % of predicted was 28.86 ± 14.51% with HFNT and 36.03 ± 19.18% with COT (p = 0.276). No significant impact was observed on dyspnea; the mean Borg scale value was 6.72 ± 2.22 after HFNT and 7.14 with COT (p = 0.56). The score for cough significantly improved after treatment with a mean score in the HFNT group being 46.67 ± 10.85 versus 73.8 ± 18.43 (p < 0.0001) with standard of care. CONCLUSIONS:Long-term HFNT significantly reduces chronic cough in patients affected by IPF compared to COT. Lung function including FVC and DLCO is not significatively influenced.

Introduction: Myotonic dystrophies (DM) are progressive genetic disorders with multisystemic involvement, particularly affecting the muscular, respiratory, and neuropsychological systems. Myotonic dystrophy type 1 (DM1), or Steinert’s disease, may lead to severe respiratory complications, including sleep-disordered breathing and hypercapnia, often requiring noninvasive ventilation to manage respiratory failure. However, adherence to NIV remains a major challenge, often influenced by cognitive and psychological factors such as apathy and depression. This study aims to investigate the presence of depression and SDB in patients with DM1 initiating NIV, and to evaluate factors influencing adherence to ventilatory support. Materials and Methods: We selected 13 adult patients (≥18 years) with diagnosis of Steinert’s disease with respiratory impairment who needed to start respiratory support. Dysphagia was assessed in all patients at baseline by a videofluoroscopic swallow study. Beck’s Depression Inventory II was administered for measuring the severity of depression. The Montreal Cognitive Assessment was used as a screening tool to detect signs of neurocognitive disorders. We evaluated adherence to NIV. Results: The study population presented with sleep-disordered breathing, as indicated by a median apnea–hypopnea index (AHI) of 24 events per hour (IQR: 14.2–34.5) and an oxygen desaturation index (ODI) of 25 events per hour (IQR: 18–33). Adherence to NIV was obtained in seven patients. No difference in baseline lung function was observed. Adherent subjects had moderate hypercapnia at baseline; pCO2 was 52 vs. 49 mmHg. Non-adherent patients showed a higher prevalence of depression with a median BDI-II score of 18 vs. 6 in adherent patients. The findings highlight that psychological factors, especially depression, play a crucial role in adherence to NIV. Interestingly, depression was not linked to initial respiratory measurements but showed a significant association with nocturnal oxygen desaturation. This suggests that relying solely on clinical and respiratory assessments may not be adequate to predict or improve treatment adherence. Conclusions: Incorporating psychological evaluations and addressing mental health issues, such as depression, are essential steps to enhance NIV compliance and overall DM1 patient outcomes. A multidisciplinary approach combining respiratory and psycho-emotional interventions is crucial for effective disease management.

IntroductionClinical 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.MethodsWe 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 FEV1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission.Results30.5% 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 FEV1% between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement.Discussionanti-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.

Background Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features. Methods We investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses. Results IL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction. Conclusion This study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.

Alpha-1 antitrypsin deficiency (AATD) is an inherited condition characterized by reduced plasma levels of alpha-1 antitrypsin (AAT), often leading to pulmonary diseases primarily emphysema and/or chronic obstructive pulmonary disease (COPD), but also bronchiectasis, bronchial asthma, or other less common disorders. Early diagnosis enables AAT augmentation therapy, which has proven to be effective in slowing down functional decline and improving survival rates. This article presents two cases of pregnant women with rare allelic variants of AATD who received AAT augmentation therapy, exploring the limited evidence on its safety during pregnancy and the potential role of decreased serum AAT levels in pregnancy-related complications.

Background/Objectives: High-flow nasal therapy (HFNT) has been shown to reduce exacerbations of COPD and some evidence displays benefits in non-cystic fibrosis bronchiectasis (NCFB) patients. The present study aimed to compare the effectiveness of 12 months of home HFNT on the annual exacerbation rate between mild/moderate and severe NCFB patients, classified by the bronchiectasis severity index (BSI). Secondary outcomes were the evaluation of the dyspnea, pulmonary function, and sputum cultures in both groups. Methods: The study population included NCFB adult patients, with at least one severe exacerbation in the previous year on optimized therapy. NCFB exacerbations, dyspnea (mMRC score), pulmonary function test, and sputum cultures were assessed at baseline and after 12 months of HFNT. Results: A total of 86 NCFB patients were enrolled: 36 in the mild/moderate (BSI < 9) and 50 in the severe (BSI ≥ 9) group. A significant improvement in the annual exacerbation rate was found in both BSI ≥ 9 (p < 0.0001) and BSI < 9 cohorts (p < 0.0001), with a between-group difference of −1 (95% CI: −2 to 0) exacerbations per year (p = 0.0209). The change in the annual exacerbation rate was significantly correlated with BSI (ρ = −0.26, p = 0.0151) and with HFNT daily use (ρ = −0.22, p = 0.0460). The mMRC score significantly improved by −2 points (95% CI: −2 to −1) after treatment in both groups (p < 0.0001). The percentage of patients with P. aeruginosa colonization decreased from 34.9% to 27.9%. Conclusions: Long-term HFNT reduces the annual exacerbation rate in NCFB patients and its effectiveness increases alongside disease severity and daily use of HFNT.

A proportion of patients with severe asthma treated with biological drugs undergoes a significant decline in F ENO. However, variations in F ENO are largely independent of the clinical efficacy of the biological drug therapy. https://bit.ly/3xWszYJ.

(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV1 and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.

Background and Aims: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. Methods: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. Results: 197 patients were included in the study (median age 83.0 [82.0–87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0–25.0] days. From the multivariable Cox regression analysis, after the application of Šidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan–Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). Conclusions: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.

Granulomatosis with Polyangiitis (GPA) is a granulomatous, necrotizing small-vessel vasculitis associated with the presence of Antineutrophil Cytoplasmic Antibodies (ANCA). In more than eighty percent of GPA patients ANCA have a Cytoplasmatic Pattern