Bruno Sposato

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition whose prognosis is shaped by exacerbations and by cardiovascular, inflammatory and metabolic comorbidity, which staging based on forced expiratory volume in one second (FEV₁) captures poorly. In this concept paper, we propose a conceptual multidimensional prognostic index, the Disease Weighted Index (DWI), together with a pre-specified programme for its derivation and validation; the work reports no model development or validation. Methods: Ten routinely available parameters were grouped into four domains: Pulmonary–Symptomatic (FEV₁, COPD Assessment Test [CAT] score, exacerbation history), Cardio–Systemic (N-terminal pro-B-type natriuretic peptide [NT-proBNP], C-reactive protein, New York Heart Association [NYHA] class), Metabolic–Nutritional (glycated haemoglobin [HbA1c], body mass index) and Demographic–Exposure (age, smoking history). Each parameter was scored on a three-level ordinal scale using guideline-based cut-offs and assigned a provisional, expert-informed weight through an explicit ordinal procedure in which the authors allocated it to a tier by judgement, guided by the adjusted effect estimates reported in the literature; these weights are specifications to be re-estimated, not established prognostic contributions. The weighted sum was normalised to a 0–100 scale. No patient-level data were used. Framework: NT-proBNP received the highest provisional weight (0.16). Four provisional risk categories (low, moderate, high and very high) were defined and linked to an expert opinion-based follow-up flowchart intended for prospective testing only. The pre-specified prediction target is a 12-month composite of severe exacerbation, all-cause hospitalisation or all-cause death. Rules for scoring when parameters are unavailable, worked examples, a conceptual comparison with the BODE, ADO, DOSE, CODEX and COTE indices, and a three-phase derivation and validation roadmap aligned with the TRIPOD statement are provided. Conclusions: The DWI is a pre-validation, testable framework that integrates the pulmonary and systemic dimensions of COPD. It is a research protocol for an index, not a validated clinical tool: its predictive performance is unproven, and it should not guide individual patient management until derivation and validation, including comparison with the unweighted sum of its items and with established indices, have been completed.

Background/Objective: Little is known about the efficacy of biologics and in particular Dupilumab in patients with severe asthma associated with COPD (SA-COPD) features. The objective of this study was to determine whether Dupilumab has similar clinical/functional efficacy in individuals with SA-COPD and in those with pure severe asthma (SA). Methods: We retrospectively selected 11 consecutive patients with SA with COPD features (smoking history of at least 15 pack/years; emphysema on chest CT scan; FEV₁ < 80%; RV and TLC > 130%; DLCO < 70; salbutamol reversibility test < 12%) treated with Dupilumab for at least 1 year. These subjects were compared with 33 consecutive patients with SA alone who were also treated with the same biologic for at least 12 months. Results: FEV₁ and FEF_25–75 changes after treatment were 10 ± 18.3% and 18.6 ± 26.5% in the SA group, whereas they were 4.8 ± 7.6% and 7.2 ± 6.8% in individuals with SA-COPD (p = 0.909 and p = 0.102 respectively). Similarly, ACT (5.3 ± 3.1 vs. 5.6 ± 3.7; p = 0.783) and exacerbation changes (−2.97 ± 1.3 vs. −4 ± 4.3; p = 0.960) after Dupilumab were similar in the two groups. No differences were also found in FeNO and BEC changes (−18 ± 22 vs. −21.3 ± 21.1 ppb and −63.6 ± 415 vs. −142 ± 299 cells/µL respectively; p = 0.984 and p = 0.481). The percentages of subjects that reduced and stopped OC therapy and those that stepped down the level of ICS dose after treatment were also similar in the two populations. After adjustment for multiple confounding factors, changes in all evaluated outcomes also remained comparable between patients with SA-COPD and those with SA. Conclusions: In our experience, Dupilumab is effective both in patients with SA alone and in those with asthma–COPD overlap. We must always consider T2 inflammation in the management of such patients in order to provide the most appropriate treatment.

Excessive Short-acting Beta-agonists Prescriptions in COPD Treated with Triple Inhaler Therapy: A Possible Marker of Frequent Exacerbations. A Retrospective Cohort Study - Thoracic Research and Practice

Background/Objective: Single-inhaler triple therapy (SITT) with budesonide/formoterol/glycopyrronium (B/F/G) is an option for COPD patients with frequent exacerbations. We evaluated its long-term efficacy in real life on emergency room visits/hospitalizations (primary endpoints), lung function, oral corticosteroid (OC), antibiotics and salbutamol (SABA) prescriptions (secondary endpoints). Methods: The aim of this single-center, retrospective observational study was to evaluate, in 65 COPD patients with recurrent exacerbations, the effects of B/F/G treatment after 18–24 months compared to therapies with LABA/LAMA, ICS/LABA, ICS/LABA + LAMA or other SITT taken in the previous 18–24 months. Results: After 22.8 ± 4.6 months, 20.12 ± 4.24 B/F/G packages were prescribed, while packs of other therapies given in the 23.35 ± 4.7 months (p = 0.587) before using B/F/G were 15.58 ± 9.8 (p = 0.0009). Emergency room visits (0.34 ± 0.56) and hospitalizations (0.52 ± 0.81) during about 2 years of B/F/G therapy were lower compared to the ones during pre-B/F/G treatments (0.65 ± 1.2, p = 0.015 and 0.83 ± 1.25, p = 0.019, respectively). After B/F/G treatment, the mean FEV₁% value (48.5 ± 16.7%) was higher compared to that measured after the therapies taken before switching to B/F/G (45 ± 15.3%; p = 0.013). Conversely, there were no differences in FVC% values. OCs (2.96 ± 2.6) and SABA (1.41 ± 2.06) packages prescribed during B/F/G were lower than those observed during pre-B/F/G treatments (3.86 ± 2.35, p = 0.026 and 2.48 ± 4.57, p = 0.046, respectively). No differences in antibiotic prescriptions were observed during both therapies. Conclusions: Our real-life evaluation highlighted that B/F/G treatment may be effective, even in the long term, in reducing exacerbations, OC and SABA consumption and in improving lung function in COPD patients with high persistence/adherence to B/F/G compared to other non-persistent inhaled therapies previously taken. Optimizing treatment adherence should be one important goal of COPD patients’ management to maximize the therapy benefits.

Following the SARS-COVID-19 pandemic the relaxation of non-pharmaceutical interventions (NPIs) and social restrictions has been associated with a notable increase in antibiotic-resistant bacteria. The purpose of this study was to evaluate the effect of the COVID-19 pandemic on clinical severity of Infective Endocarditis (IE) among in-patients before, during, and after the pandemic. A retrospective population study was conducted from January 1, 2017, to January 1, 2025, involving consecutive patients diagnosed with endocarditis at a referral hospital in Tuscany, Italy. The patients were stratified into three groups: pre-pandemic (2017–2019), pandemic (2020–2021), and post-pandemic (2022–2025). During the study period, a total of 187 confirmed hospitalised cases of IE were diagnosed, temporally divided as follows: 86 pre-pandemic, 35 during the pandemic, and 67 post-pandemic. The incidence of S. Aureus-related IE admissions increased significantly (23.20% pre-pandemic vs. 29.40% during the pandemic vs. 44.7% post-pandemic, p=0.022). The incidence of MRSA-related IE admissions increased but not significantly (10.50% pre-pandemic vs. 33.30% during the pandemic vs. 20.0% post-pandemic, p=0.389). Sepsis shock was more frequent (34.9% pre-pandemic vs 55.9% during the pandemic vs 53.7% post-pandemic, p=0.044). "Mortality rates were notably elevated during the pandemic and remained higher in the post-pandemic period (29.40% and 32.80%, respectively) compared to the pre-pandemic period (18.60%; p=0.018). The increased incidence of systemic sepsis was identified as a strong independent predictor of in-hospital mortality. In conclusion in-hospital mortality from infective endocarditis has remained elevated post-pandemic, largely due to the increased systemic severity linked to a rise in more and resistant bacterial infections

It remains unclear whether baseline FENO levels can predict response to anti-IL5/5R biologic treatment in patients with severe asthma. We recruited 104 patients with severe eosinophilic asthma treated with anti-IL5/anti-IL5R for at least one year who had measured FeNO values before the beginning of anti-eosinophilic treatment. Population was divided into subjects with FeNO < 25 and ≥25 ppb. In each group we evaluated the changes in pulmonary function (FEV₁% and FEF_25-75%), clinical (ACT and exacerbations) and steroid-sparing effect, expressed as the modification of daily dosage of inhaled corticosteroids (ICS) and oral corticosteroids (OC), after anti-IL5/anti-IL5R. FEV₁ changes after treatment were 3.34 ± 15,97% in subjects with low baseline FeNO, whereas 11.2 ± 16.1% in individuals with FeNO ≥ 25 ppb (p = 0.012). Also, FEF_25-75% variations after treatment were different in the two groups: 2.1 ± 10.7% vs 9.6 ± 18% in individuals with FeNO < 25 and ≥25 respectively (p = 0.05). Conversely, ACT (4.4 ± 4.2 vs 5.9 ± 4.6;p = 0.147), exacerbation changes (-2.46 ± 1.5 vs 2.9 ± 1.6;p = 0.137) after treatment were similar in both groups where ICS dosages reduction was alike. On the contrary, the percentage of subjects that reduced/stopped OC treatment after anti-IL5/anti-IL5R was 71.7% in the group with FeNO < 25 ppb whereas 94.1% in individuals with FeNO ≥ 25 (p = 0.06). Multivariate analysis adjusted for all confounding factors also confirmed the relationship between FeNO ≥ 25 and improvement in FEV₁%/FEF_25-75% ((β = 8.372,p = 0.013 and β = 8.883;p = 0.062 respectively) and the increased probability of discontinuing/reducing OC use (OR:17.838[95%CI:3.159-100.730];p = 0.001). Pre-biologic FeNO might predict a greater response to treatment with anti-IL-5/5R especially in terms of lung function and OC sparing in subjects with severe eosinophilic/allergic asthma. This could likely be a biomarker that can better guide in choosing an anti-IL5/5R in severe overlapping asthma (eosinophilic/allergic) to maximize treatment effects.

Background: Today, single-inhaler ICS/LAMA/LABA (SITT) COPD therapies are available. It is unclear whether they are more effective than multiple-device triple therapies (MITT) in improving COPD outcomes. Methods: We retrospectively considered patients on SITT/MITT in 2019/2020 who were prescribed >7 packages of ICS/LABA/LAMA or ICS/LAMA (+LAMA). The two treatments were compared concerning systemic corticosteroids, antibiotics, salbutamol, antifungal prescriptions, and number of emergency room visits/hospitalizations (ERV/Hs). We studied 292 MITT patients (Group A) during 2019, switching to SITT in 2020, and 366 subjects (Group B) who took SITT during 2019, and 206 MITT individuals (Group C) in 2020. Results: ICS/LABA + LAMA (MITT) package use was 8.2 ± 4.2 and 7.85 ± 4 in 2019, switching to 11.2 ± 3.2 when patients shifted to SITT in 2020 (p = 0.0001). Group A MITT package use was lower than in SITT patients in 2019 (9.31 ± 2.71, p = 0.0001; Group B). Throughout 2020, Group C (10.3 ± 6.1 packs) adherence to ICS/LABA was similar to SITT adherence in Group A (p = 0.270), whereas LAMA package use (9.1 ± 5) was lower (p = 0.0038). Patients using systemic corticosteroids/antibiotics were fewer in SITT in 2020, compared to the MITT results in 2019. Subjects with fewer ERV/Hs were observed with SITT rather than with MITT. Particularly, 13.8% of patients needed ≥2 ERV/Hs when treated with SITT, whereas 19.2% needed ≥2 ERV/Hs with MITT in 2019 (p = 0.08). Multivariate analysis, adjusted for all confounding factors including treatment adherence, showed that MITT (vs. SITT) can have an increased risk of at least one ERV/H (subjects receiving MITT during 2019 passing to SITT in 2020, OR: 1.718 [1.010–2.924], p = 0.046; Group A/MITT/2019 vs. Group B/SITT/2019, OR: 1.650 [0.973–3.153], p = 0.056; Group C/MITT/2020 vs. Group B/SITT/2019, OR: 1.908 [1.018–3.577], p = 0.044). Conclusions: SITT therapy may promote treatment adherence more effectively, therefore, reducing COPD exacerbations better than MITT. A possible synergistic effect of ICS/LABA/LAMA intake with a single device might be another cause of SITT’s greater efficacy.

Background: The role of inhaled Nitric Oxide (iNO) in managing Acute Respiratory Distress Syndrome Covid-19 related (C-ARDS) is debatable. The study aimed to analyze the effect of iNO administration in patients with persistent severe hypoxia and Intensive Care Unit (ICU) mortality. Methods: This retrospective study included 98 consecutive critically ill patients with C-ARDS admitted to ICU from 1 October 2020 to 31 October 2021. Results: Of these patients, 28% had received iNO. Twelve (44.4%) were responders. Kaplan-Mayer plot shows mortality was higher in non-responders (86.6 vs 25.0%). Non-response to iNo was the most important predictive value (p. 0.01). The Receiver Operating Characteristic (ROC) curve for a percentage increase in PaO2 from baseline confirmed that it had a higher predictive value for in-hospital survival. A value of 19% can predict the death event with a sensitivity of 81.8% and a specificity of 81.2%. Conclusions: Therefore, we propose to use iNO as a vasoreactivity test for prognostic stratification in patients with persistent severe hypoxia.

Background: The prevalence of clinical asthma remission with biologics in severe asthma has not been well understood yet. We do not even know whether there might be characteristics that identify subjects prone to remission of the disease. Materials and Methods: Retrospectively, four groups of severe asthmatics already treated with Omalizumab, Mepolizumab, Benralizumab and Dupilumab (302, 55, 95 and 34 patients, respectively) for at least 12 months were considered. The number of individuals with clinical asthma remission was sought in each group. This was considered when patients, after a treatment of at least 1 year with one of the aforesaid biologics, showed the disappearance of asthma symptoms (ACT ≥ 20), zero exacerbations, suspension of oral corticosteroids and a FEV₁% ≥ 80%. Baseline characteristics of patients with and without remission were also taken into account. Results: The prevalence of asthma remission after a mean of 37.8 ± 19.2, 13.5 ± 1.7, 15.4 ± 5.5 and 12 ± 0 months of Omalizumab, Mepolizumab, Benralizumab and Dupilumab treatments was 21.8%, 23.6%, 35.8% and 23.5%, respectively. For each biologic, different baseline characteristics, seem to be associated with failure to achieve clinical asthma remission. Older age, higher BMI, a later age of asthma onset, rhinitis/sinusitis/nasal polyposis, comorbidities and a greater asthma severity may be the characteristics of a suboptimal response to biologic treatments. Conclusion: All biologics have the potential to induce disease remission in severe asthmatics. For each biologic, there may be several markers that can identify the patients who will not achieve asthma remission. It would be important to detect them (by carrying out targeted studies) as they would allow us to select the best biologic that may induce clinical asthma remission on a larger number of patients.

Background and Objective: In 2020, Italy was one of the most affected countries in the world, counting over 70.000 deaths for covid-19. The Italian ministry of health led the nationwide vaccination campaign. On 1st september 2021, 72% of the population received at least one dose. We aimed to...