Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T- and NK-cells negatively regulate the T-cell immune function. The present study aimed to explore the peripheral distribution of IC molecules to better elucidate their peripheral tolerance failure, which might reflect the development of diseases. Patients referred to Respiratory Diseases and Rheumatology Unit of Siena University Hospital were prospectively and consecutively enrolled. Healthy subjects were also enrolled as a control group. Multicolor flow cytometric analysis was performed to detect IC molecules in the peripheral blood of patients. Twenty-three patients were consecutively and prospectively enrolled in the study: 11 patients had an AAV diagnosis and 12 had sarcoidosis. CD4⁺PD1⁺ cells were higher in sarcoidosis and GPA than in HC (p = 0.0250 and p = 0.0253, respectively). CD56⁺CTLA4⁺ were higher in sarcoidosis than GPA, MPA and HC (p = 0.0085, p = 0.0042 and p = 0.0004, respectively). CTLA4⁺NK cells clustered for 100% of sarcoidosis patients according to decision tree analysis, while PD1⁺CD4 and CD8 cells for clustered for 100% of GPA patients. Our analyses showed substantial differences between sarcoidosis and AAV, further confirming the immunological peculiarity of this disease. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with the hope to open up new therapeutic avenues and, if possible, to develop preventive measures.

(1) Background: Sarcoidosis is a chronic multisystem disorder of unknown aetiology, driven by a T-cell mechanism allowing T-cell attachment and transmigration through the endothelium, and endorsed by the expression of an integrin alpha-E beta-7 (CD103). This study aimed to analyse the different distribution and compartmentalisation of CD103 expression on T cell subsets in BAL, peripheral blood mononuclear cells (PBMC) and lymph nodes (LLN) from sarcoidosis patients. (2) Patients: We consecutively and prospectively enrolled 14 sarcoidosis patients. We collected PBMC, LLN and BAL at the same time from all patients. Through flow cytometric analysis, we analysed the expression of CD103 on regulatory and follicular T cell subsets. (3) Results: All patients were in radiological Scadding stage II. The multivariate analysis found that the variables which most influenced the peripheral blood compartment were high CD8⁺ and low ThReg, CD8⁺CD103⁺ and Tfh cell percentages. A principal component analysis plot performed to distinguish LLN, BAL and PBMC showed that they separated on the basis of CD4⁺, CD4⁺CD103⁺, CD8⁺, CD8⁺CD103⁺, TcEffector, TcNaive, ThNaive, ThEffector, Threg, ThregCD103⁺, Tfh, TcfCXC5⁺ and CD4⁺CD103⁺/CD4⁺ with 65.96% of the total variance. (4) Conclusions: Our study is the first to report a link between the imbalance in circulating, alveolar and lymph node CD8⁺ and CD8⁺CD103⁺ T cells, ThReg, Tfh and ThNaive and the CD103⁺CD4⁺/CD4⁺ T cell ratio in the development of sarcoidosis. These findings shine a spotlight on the pathogenesis of sarcoidosis and may offer new predictors for diagnosis. Our study provides additional understanding for a personalised, and hopefully more effective treatment of sarcoidosis.

Purpose of Review: 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 Findings: 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. Summary: 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.

Tuberculous pleural effusion (TPE) is currently the most common form of extrapulmonary tuberculosis and remains a significant cause of pleural disease worldwide, particularly in endemic regions. It often presents with non-specific clinical symptoms, such as fever, chest pain, cough and weight loss, thereby complicating the diagnostic process. This narrative review provides an expert comprehensive clinical practice overview covering the following issues correlated with diagnosis and management of TPE: 1- epidemiology, clinical presentation and underlying pathophysiology; 2- limitations of conventional diagnostic procedures on pleural fluid; 3- usefulness of thoracic ultrasound (TUS) in the stepwise pathway 4- role of thoracoscopy as a golden diagnostic tool, with the proposal of a step by step algorithm. A large iconography enriches the review from the educational point of view by presenting a pictorial series of characteristic sonographic and thoracoscopic findings.

Biologic therapies for eosinophilic COPD require a blood eosinophil count (BEC) ≥300 cells/µL for eligibility. Landmark trials used a single screening measurement, yet BEC exhibits substantial within-patient variability. The study aimed to evaluate the optimal number of measurements to reliably detect the eosinophilic phenotype in COPD. We developed a decision-analytic simulation model using pooled estimates of BEC variability from independent COPD cohorts, with intraclass correlation coefficients (ICCs) pooled using Fisher's z transformation. Persistence data from five cohorts - ECLIPSE, COSYCONET, CHAIN, BODE, and a Swedish cohort - comprising a total of 3347 patients, were used to estimate the probability of detecting BEC ≥300 cells/µL at least once according to the number of serial measurements. Using the ≥300 cells/µL threshold, the pooled COPD population was classified as persistent eosinophilia, 9.2%; intermittent eosinophilia, 32.5%; and never eosinophilic, 58.3%. Among patients with intermittent eosinophilia, one measurement detected BEC ≥300 cells/µL in 43% of cases. Two measurements at 6-month intervals increased detection to 67%, three measurements over 12 months to 81%, and five measurements over 24 months to 94%. Weighted pooled ICCs declined from 0.784 at ≤3 months to 0.570 at ≥36 months, supporting greater variability over longer intervals. Intermittent eosinophilia affects approximately one-third of patients with COPD and may be missed by single-BEC screening. In this model, three measurements over 12 months achieved ≥80% detection. Integrating historical and prospective BEC values may improve biologic eligibility assessment without delaying treatment decisions.

Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5–R20) and spirometry FEF25–75% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV₁, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5–R20 > 0.07 kPa/L/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5–R20 decreased from 0.18 ± 0.17 kPa/L/s to 0.09 ± 0.07 at T12 (p = 0.04), while predicted FEF25–75% increased from 29.5 ± 20.8% to 47.0 ± 21.1% (p < 0.001). ACT scores improved from 13.1 ± 4.9 to 19.6 ± 3.8 (p < 0.001). FeNO levels declined from 64.1 ± 50.7 ppb to 24.8 ± 20.9 ppb (p = 0.01). Improvements in R5–R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months.