Clinical Remission in Patients Affected by Severe Eosinophilic Asthma on Dupilumab Therapy: A Long-Term Real-Life Study.

Background. Nowadays, highly selective biological drugs offer the possibility of treating severe type 2 asthma. However, in the real-life setting, it is crucial to confirm the validity of the chosen biological treatment by evaluating the achievement of clinical remission. Study purpose. The main aims of this real-life study were to evaluate the efficacy of dupilumab in terms of clinical, functional, and inflammatory outcomes at 6, 12, 18, and 24 months of treatment and to estimate the percentage of patients achieving partial or complete clinical remission at 12 and 24 months of treatment. In addition, we attempted to identify whether baseline clinical characteristics of patients could be associated with clinical remission at 24 months of treatment. Materials and methods. In this observational prospective study, 20 outpatients with severe uncontrolled eosinophilic asthma were prescribed dupilumab and followed-up after 6, 12, 18, and 24 months of treatment. At each patient visit, the need for oral corticosteroids (OCS) and corticosteroid required dose, number of exacerbations during the previous year or from the previous visit, asthma control test (ACT) score, pre-bronchodilator forced expiratory volume in the 1st second (FEV1), fractional exhaled nitric oxide at a flow rate of 50 mL/s (FeNO50), and blood eosinophil count were assessed. Results. The number of OCS-dependent patients was reduced from 10 (50%) at baseline to 5 (25%) at one year (T12) and 2 years (T24). The average dose of OCS required by patients demonstrated a significant reduction at T12 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.015), remaining significant even at T24 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.016). The number of exacerbators showed a statistically significant decrease at T24 (10 patients, 50% vs. 3 patients, 15%, p = 0.03). The mean number of exacerbations demonstrated a statistically significant reduction at T24 (1.45 ± 1.58 vs. 0.25 ± 0.43, p = 0.02). The ACT score improved in a statistically significant manner at T12 (15.30 ± 4.16 vs. 21.40 ± 2.35, p < 0.0001), improving further at T24 (15.30 ± 4.16 vs. 22.10 ± 2.59, p < 0.0001). The improvement in pre-bronchodilator FEV1 values reached statistical significance at T24 (79.5 ± 14.4 vs. 87.7 ± 13.8, p = 0.03). The reduction in flow at the level of the small airways (FEF25-75%) also demonstrated an improvement, although it did not reach statistical significance either at T12 or T24. A total of 11 patients (55%) showed clinical remission at T12 (6 complete + 5 partial) and 12 patients (60%) reached clinical remission at T24 (9 complete + 3 partial). Only obesity was associated with a negative odds ratio (OR) for achieving clinical remission at T24 (OR: 0.03, 95% CI: 0.002-0.41, p = 0.004). No other statistically significant differences in baseline characteristics emerged between patients who reached clinical remission at T24 and the group of patients who did not achieve this outcome. Conclusion. Dupilumab appears to be an effective drug in promoting achievement of clinical remission in patients with severe uncontrolled eosinophilic asthma. The achievement of clinical remission should be continuously evaluated during treatment. Further studies are needed to clarify whether certain baseline clinical characteristics can help predict dupilumab favorable outcomes.

Imaging Profile After Treatment with Tocilizumab in COVID-19: A Case Series.

INTRODUCTION: COVID-19 is a pandemic disease, mainly affecting the respiratory tract, triggering an inflammatory cascade complicated by multiorgan failure up to death. Among the tested medications for this disease, tocilizumab appears to act directly on the inflammatory cascade, improving COVID-19 outcomes. For this reason, we have tested the efficacy of tocilizumab on lung damage using chest computed tomography (CT). CASE PRESENTATION: The study was conducted on twenty-one hospitalised COVID-19 patients between March-June 2020. Patients were divided into 2 groups according to the therapies administered (TCZ group= treatment with tocilizumab and NTZ group= other therapies). At admission, TCZ group presented worse laboratory test values, respiratory profile (PaO2/FiO2 ratio: 145.37±38.16 mmHg vs 257.9±95.3 mmHg of NTZ group, P<0.01) and radiological signs (multifocal opacity at chest-X-ray: 88% vs 23% of NTZ group, P<0.01). After performing chest CT during the clinical recovery, the scans of the 2 groups were compared and we observed that some features (e.g., ground glass opacity, consolidation and parenchymal bands) were less marked in the TCZ group. CONCLUSION: In our study, patients treated with tocilizumab presented a worse overall clinical and radiological profile at admission, but the control CT showed a similar imaging profile to patients treated with standard therapy. Based on this evidence, we may suggest that tocilizumab plays an important role in COVID-19 patients in reducing lung inflammation.

Watch the Mime Carefully! A Refractory Interstitial Lung Disease.

Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of a vascular origin which can arise in different locations such as the lungs, liver, soft tissue, and rarely, in the bones. In the lungs, pulmonary hemangioendothelioma (PEH) shows a variable clinical behavior, displaying a range from either an asymptomatic course to a highly aggressive progression with metastases. Based on radiological features, PEH differential diagnosis mainly includes primary or metastatic lymphangitic carcinomatosis, granulomatous infections, and diffuse interstitial lung diseases where ground glass pattern predominates. In this case, a transbronchial biopsy and subsequent histological and immunohistochemical analysis allowed for the attribution of the scenario to a pulmonary epithelioid hemangioendothelioma. Clinicians should always consider bronchoscopy as a useful and effective tool to better investigate indeterminate and questionable clinical pictures, sparing patients the morbidity and mortality associated with more invasive techniques such as surgical or thoracoscopic biopsy.

Handling and standardization of EBUS needle aspiration in NSCLC patients: The value of the cell block, a monoinstitutional experience.

BACKGROUND: Lung cancer is the main cause of cancer-related death worldwide, and 85% of all lung tumors are non-small cell lung cancers (NSCLC). More than 60% of all lung tumors are diagnosed at an advanced stage, leading to poor prognosis. Given the growing demand for NSCLC profiling for selection of the most appropriate therapy, the acquisition of adequate tumor samples has become increasingly crucial, mostly in advanced NSCLC patients due to old age and/or comorbidities. Being a mini-invasive sampling technique, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) represents a valuable alternative to traditional transthoracic or surgical sampling in these patients, and perfoming cell block (CB) could be crucial to maximize the potential biological information. The aim of this study is to describe a monoinstitutional interprofessional experience in handling EBUS-TBNA and CB in 464 patients. METHODS: We retrospectively collected all the consecutive CBs obtained from EBUS TBNA performed between 2014 and 2021 on the lung lesions or mediastinal lymph nodes. All the CBs were handled in a standardized method. RESULTS: A total of 95.5% (448/464 samples) of adequacy for site and 92.6% (430/464) of adequacy for diagnosis were observed. Moreover, in the adenocarcinoma histotype, ALK, ROS1 and tumor proportion score (TPS) PD-L1 assessment by IHC was possible in 96% (140/146) of cases, and molecular profile was obtained in 93.8% (137/146) of cases. In the squamous cell carcinoma histotype, TPS PD-L1 assessment was possible in 81% (13/16) of cases. All four CB results obtained from carcinoma NOS were adequate for ALK, ROS1 and PD-L1 assessment and molecular profiling. All 39 metastatic samples from extra-pulmonary primary were adequate for immunohistochemical characterization and molecular profiling. Finally, reporting of the tumor sample adequacy to the clinicians took a median time of about 30 h (range: 24-80 h). CONCLUSION: Careful cytological smear management together with the handling and standardization of CB obtained from EBUS-TBNA could represent an effective method to increase the adequacy of the tumor specimen for both diagnosis and molecular profile.

Effectiveness and Safety of Real-Time Transthoracic Ultrasound-Guided Thoracentesis.

PURPOSE: The purpose of the present study was to specifically evaluate the effectiveness and safety of real-time ultrasound-guided thoracentesis in a case series of pleural effusion. PATIENTS AND METHODS: An observational prospective study was conducted. From February 2018 to December 2019, a total of 361 consecutive real-time transthoracic ultrasound (TUS)-guided thoracentesis were performed in the Unit of Diagnostic and Interventional Ultrasound of the Research Hospital "Fondazione Casa Sollievo della Sofferenza" of San Giovanni Rotondo, Foggia, Italy. The primary indication for thoracentesis was therapeutic in all the cases (i.e., evacuation of persistent small/moderate pleural effusions to avoid super-infection; drainage of symptomatic moderate/massive effusions). For completeness, further diagnostic investigations (including chemical, microbiological, and cytological analysis) were conducted. All the procedures were performed by two internists with more than 30 years of experience in interventional ultrasound using a multifrequency convex probe (3-8 MHz). For pleural effusions with a depth of 2-3 cm measured at the level of the costo-phrenic sinus was employed a dedicated holed convex-array probe (5 MHz). RESULTS: In all the cases, the attempts at thoracentesis were successful, allowing the achievement of the therapeutic purpose of the procedure (i.e., the complete drying of the pleural space or the withdrawal of fluid till a "safe" quantity [a mean of 1.5 L, max 2 L] producing relief from symptoms) regardless of the initial extent of the pleural effusion. There were only 3 cases of pneumothorax, for a prevalence rate of complications in this population of 0.83%. No statistical difference was recorded in the rate of pneumothorax according to the initial amount of pleural fluid in the effusion (p = 0.12). All the pleural effusions classified as transudates showed an anechoic TUS appearance. Only the exudative effusions showed a complex nonseptated or a hyperechoic TUS appearance. However, an anechoic TUS pattern was not unequivocally associated with transudates. Some chronic transudates have been classified as exudates by Light's criteria, showing also a complex nonseptated TUS appearance. The cytological examination of the drained fluid allowed the detection of neoplastic cells in 15.89% cases. On the other hand, the microbiological examination of effusions yielded negative results in all the cases. CONCLUSIONS: Real-time TUS-guided thoracentesis is a therapeutically effective and safe procedure, despite the diagnostic yield of the cytological or microbiological examinations on the collected liquid being very low. Future blinded randomized studies are required to definitely clarify the actual benefit of the real-time TUS-guided procedure over percussion-guided and other ultrasound-based procedures.

Chylothorax found in a patient with COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its clinical spectrum ranges from mild to moderate or severe illness. A 78-year-old male was presented at emergency department with dyspnoea, dry cough and severe asthenia. The nasopharyngeal swab by real-time polymerase chain reaction confirmed a SARS-CoV-2 infection. The x-ray and the thoracic ultrasound revealed right pleural effusion. A diagnostic-therapeutic thoracentesis drained fluid identified as chylothorax. Subsequently, the patient underwent a chest computed tomography which showed the radiological hallmarks of COVID-19 and in the following weeks he underwent a chest magnetic resonance imaging to obtain a better view of mediastinal and lymphatic structures, which showed a partial thrombosis affecting the origin of superior vena cava and the distal tract of the right subclavian vein. For this reason, anticoagulant therapy was optimized and in the following weeks the patient was discharged for clinical and radiological improvement. This case demonstrates chylothorax as a possible and uncommon complication of COVID-19.

Impact of smoking, COPD and comorbidities on the mortality of COVID-19 patients.

The prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.

Effectiveness of Benralizumab in Improving the Quality of Life of Severe Eosinophilic Asthmatic Patients: Our Real-Life Experience.

Background: Severe eosinophilic asthma decreases lung function and causes worsen symptoms, often forcing recurrent maintenance corticosteroid use. The aim of our real-life study was to evaluate the effectiveness of an add-on treatment with benralizumab in patients with severe eosinophilic asthma, paying particular attention to the impact on their quality of life (QoL). Materials and methods: In this prospective study, 10 outpatients with severe eosinophilic asthma were added-on with benralizumab and followed-up in our severe asthma clinic after 12 and 24 weeks. At each patient visit, pre-bronchodilator FEV1 and inflammatory markers were recorded. Variations in asthma symptoms control and QoL perception was assessed by validated questionnaires. Results: All the subjects experienced a marked reduction of nocturnal and diurnal symptoms over time and were able to stop using OCS, as documented by the improvement in Asthma control test (ACT) and Asthma Control Questionnaire score. Similarly, we recorded a statistically significant increase in patient's QoL perception in EQ-VAS, EQ-5D-3L and Asthma Quality of Life Questionnaire (AQLQ) assessment (p < 0.05). Simultaneously we recorded a significant reduction in eosinophilic inflammation, an improvement in pre-bronchodilator FEV1. These results appear to be in line with those already obtained in the previous randomized controlled trials (RCTs). Conclusion: Our 24-weeks real life experience supports the effectiveness of an add-on treatment with benralizumab in reducing eosinophilic inflammation and OCS-use, increasing lung function and improving control of nocturnal and diurnal symptoms, as well as restoring severe asthma patients to a better QoL.

The Role of Airways 17ß-Estradiol as a Biomarker of Severity in Postmenopausal Asthma: A Pilot Study.

BACKGROUND: Asthma severity differs according to gender; in adult women, there is higher prevalence and severity of asthma than in men, and it coincides with changes in sex hormones. Recently, a new phonotype of asthma has been identified that appears after menopause, and it may be associated with decreased estrogen levels. Our goal was to study the 17ß-estradiol (E2) concentrations in the blood and airways of women affected by asthma onset after menopause, evaluating its possible role in the severity of the disease. METHODS: We enrolled 33 consecutive women with a diagnosis of postmenopausal asthma, recruited from the outpatient pulmonary clinic: 18 with severe (SA) and 15 with mild-to-moderate (MMA) asthma. We also included 30 age-matched healthy menopausal women as controls (HS). All subjects enrolled underwent blood and sputum collection (IS), and E2 concentrations were determined in plasma and sputum supernatant samples using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Significantly higher serum concentrations of E2 were found in postmenopausal SA compared to MMA and HS, respectively (33 ± 5.5 vs. 24 ± 6.63 vs. 7.79 ± 1.54 pg/mL, p < 0.05). Similar results were found in the IS: significantly higher levels of E2 were detected in patients with postmenopausal SA compared with MMA and HS, respectively (0.34 ± 0.17 vs. 0.26 ± 0.13 vs. 0.07 ± 0.06 pg/mL, p < 0.05). We found positive correlations between IS E2 concentrations and sputum neutrophil levels in SA group (ρ = 0.52, p < 0.05). CONCLUSIONS: Our findings showed the possibility to measure E2 in the airways, and it has increased in postmenopausal asthmatic patients, especially in those with SA. Airways E2 levels may serve as a suitable biomarker of postmenopausal SA to help to phenotype SA patients with neutrophil inflammation.