Purpose: Hypovitaminosis D is a highly spread condition correlated with increased risk of respiratory tract infections. Nowadays, the world is in the grip of the Coronavirus disease 19 (COVID 19) pandemic. In these patients, cytokine storm is associated with disease severity. In consideration of the role of vitamin D in the immune system, aim of this study was to analyse vitamin D levels in patients with acute respiratory failure due to COVID-19 and to assess any correlations with disease severity and prognosis. Methods: In this retrospective, observational study, we analysed demographic, clinical and laboratory data of 42 patients with acute respiratory failure due to COVID-19, treated in Respiratory Intermediate Care Unit (RICU) of the Policlinic of Bari from March, 11 to April 30, 2020. Results: Eighty one percent of patients had hypovitaminosis D. Based on vitamin D levels, the population was stratified into four groups: no hypovitaminosis D, insufficiency, moderate deficiency, and severe deficiency. No differences regarding demographic and clinical characteristics were found. A survival analysis highlighted that, after 10 days of hospitalization, severe vitamin D deficiency patients had a 50% mortality probability, while those with vitamin D ≥ 10 ng/mL had a 5% mortality risk (p = 0.019). Conclusions: High prevalence of hypovitaminosis D was found in COVID-19 patients with acute respiratory failure, treated in a RICU. Patients with severe vitamin D deficiency had a significantly higher mortality risk. Severe vitamin D deficiency may be a marker of poor prognosis in these patients, suggesting that adjunctive treatment might improve disease outcomes.

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV₁) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed “Quiet Asthma”.

The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of millions of individuals and caused millions of deaths worldwide. Predicting the clinical course of the disease is of pivotal importance to manage patients. Several studies have found hematochemical alterations in COVID-19 patients, such as inflammatory markers. We retrospectively analyzed the anamnestic data and laboratory parameters of 303 patients diagnosed with COVID-19 who were admitted to the Polyclinic Hospital of Bari during the first phase of the COVID-19 global pandemic. After the pre-processing phase, we performed a survival analysis with Kaplan–Meier curves and Cox Regression, with the aim to discover the most unfavorable predictors. The target outcomes were mortality or admission to the intensive care unit (ICU). Different machine learning models were also compared to realize a robust classifier relying on a low number of strongly significant factors to estimate the risk of death or admission to ICU. From the survival analysis, it emerged that the most significant laboratory parameters for both outcomes was C-reactive protein min; $HR=17.963$ (95% CI 6.548–49.277, p < 0.001) for death, $HR=1.789$ (95% CI 1.000–3.200, p = 0.050) for admission to ICU. The second most important parameter was Erythrocytes max; $HR=1.765$ (95% CI 1.141–2.729, p < 0.05) for death, $HR=1.481$ (95% CI 0.895–2.452, p = 0.127) for admission to ICU. The best model for predicting the risk of death was the decision tree, which resulted in ROC-AUC of 89.66%, whereas the best model for predicting the admission to ICU was support vector machine, which had ROC-AUC of 95.07%. The hematochemical predictors identified in this study can be utilized as a strong prognostic signature to characterize the severity of the disease in COVID-19 patients.

Background: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. It demonstrated its efficacy in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting.Methods: We included 12 patients with severe, uncontrolled asthma and dupilumab was chosen if there was at least one evidence of blood eosinophils >150 cells/ml and/or FeNO >25 ppb during last year. Recent blood eosinophil count report, assessment through ACT, FeNO test and spirometry were performed at baseline and after 3 months of treatment. We calculated also the number of patients achieving a minimal, yet clinically relevant difference in FEV1 and ACT.Results: After three months of treatment with dupilumab, ACT had a significant improvement (mean ACT pre 13.25±4.65 vs mean ACT post 19.17±4.45; p<0.01), so as FEV1% (mean FEV1% pre 62.58±15.73 vs mean FEV1% post 71.00±13.11; p<0.01). FeNO had a significant reduction (median FeNO 32 pre, IQR 19-48.5 vs median FeNO19 post, IQR 16.5-26), differently from eosinophils blood count (median eosinophils pre 280, IQR 193.8-647.3 vs median eosinophils post 349.5, IQR 103-836.8; p=0.52). Four patients (33%) had a positive MCID for FEV1, and eight patients (67%) had a positive MCID for ACT.Conclusions: In RCTs performed during clinical development program dupilumab showed an early efficacy in increasing FEV1, reducing FeNO and improving asthma control. Our study demonstrates early improvement in asthmatic symptoms, lung function and FeNO in severe type-2 asthma patients after only 3 months of dupilumab biologic therapy. The introduction of FeNO levels evaluation in the selection criteria for dupilumab, further helps the identification of eligible patients among type-2 severe asthma patients and lets a complete outpatient assessment. Further real-life studies with a longer follow-up time will be useful to confirm dupilumab efficacy and to promote its use in clinical practice.