Mortality trends in idiopathic pulmonary fibrosis in Europe between 2013 and 2018.

BACKGROUND: Previous research has suggested that the incidence of idiopathic pulmonary fibrosis (IPF) is increasing in the UK and elsewhere. The aim of this study is to provide contemporary estimates of IPF mortality rates across 24 European Union (EU) countries from 2013 to 2018, using death certificate data from the European Statistics Institution (EUROSTAT) database. METHODS: We extracted country data for IPF (International Classification of Diseases, 10th Revision: code J84.1) mortality from the EUROSTAT dataset. We calculated country-, age- and sex-specific death registration rates between 2013 and 2018. We used direct standardisation to compare rates between countries. We calculated annual trends in mortality rate ratios using a segmented regression model. RESULTS: The overall standardised mortality rate in 24 EU countries during this period was 3.90 (95% CI 3.80-3.90) per 100 000 person-years, with the rate rising from 3.70 in 2013 to 4.00 in 2018 (average annual percent change 1.74%, 95% CI 0.91-2.59%). We observed substantial inter-country differences, with the highest rates detected in Ireland, the UK and Finland, the lowest rate in Bulgaria, and middle rates in Germany, Greece, Italy, the Netherlands, Portugal and Slovenia. CONCLUSIONS: The IPF mortality rate is increasing across Europe. There are currently more than 17 000 deaths recorded from IPF each year in Europe but the marked geographical differences we observed suggest that this figure may underestimate the true rate considerably.

Understanding Patterns of Adherence to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis: Insights from an Italian Prospective Cohort Study.

Background: Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014-2021 in newly diagnosed IPF patients, using Healthcare Utilization Databases of the Marche Region, Italy. Methods: The first 12-month adherence to antifibrotic was estimated using the Proportion of Days Covered (PDC), defining adherence as PDC ≥ 75%. State Sequence Analysis over the initial 52 weeks of treatment was used to identify adherence patterns. The role of adherence patterns on acute exacerbations/death, adjusted by demographic, clinical features, and monthly adherence after the 52-week period (time-dependent variable), was assessed with Cox regression. Results: Among 667 new IPF cases, 296 received antifibrotic prescriptions, with 62.8% being adherent in the first year. Three antifibrotic utilization patterns emerged-high adherence (37.2%), medium adherence (42.5%), and low adherence (20.3%)-with median PDCs of 95.3%, 79.5%, and 18.6%, respectively. These patterns did not directly influence three-year mortality/exacerbation probability, but sustained adherence reduced risk over time. Conclusions: Good adherence was observed in in this population-based study, emphasizing the importance of continuous antifibrotics therapy over time to mitigate adverse outcomes.

Malignant pleural effusion: current understanding and therapeutic approach.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

Management of malignant pleural effusion in Italian clinical practice: a nationwide survey.

BACKGROUND: Pleural disease (PD), particularly malignant pleural effusion (MPE), is a common cause of hospital admission and its prevalence is rising worldwide. Recent advances in diagnostic and therapeutic options, such as Indwelling Pleural Catheters (IPCs), have simplified PD treatment, allowing an effective outpatients management. Therefore, dedicated pleural services can improve PD care, guaranteeing specialized management and optimizing time and cost. We aimed to provide an overview on MPE management in Italy, mainly focused on distribution and characteristics of pleural services and IPCs use. METHODS: A nationwide survey, endorsed by the Italian Thoracic Society, was distributed by email to members of selected subgroups in 2021. RESULTS: Ninety (23%) members replied, most of whom being pulmonologists (91%). MPE resulted the most common cause of pleural effusion and was managed with heterogenous approaches, including talc pleurodesis via slurry (43%), talc poudrage (31%), repeated thoracentesis (22%) and IPCs insertion (2%). The setting of IPC insertion was inpatient care in 48% of cases, with a predominance of draining frequency every other day. IPC management mainly relied on caregivers (42%). The presence of a pleural service was reported by 37% of respondents. CONCLUSIONS: The present study provides an extensive overview of MPE management in Italy, showing a highly heterogeneous approach, a scarce prevalence of out-patient pleural services, and a still limited adoption of IPCs, mainly due to lack of dedicated community care systems. This survey emphasizes the need of promoting a higher spreading of pleural services and an innovative healthcare delivery with more favourable cost-benefit ratio.

Possible Use of Linear Echobronchoscope for Diagnosis of Peripheral Pulmonary Nodules.

Echobronchoscope-guided transbronchial needle aspiration (EBUS-TBNA) is mainly used as the transbronchial approach to hilar/mediastinal lymph nodes or lesions, for diagnostic or staging purposes. Moreover, the role of linear EBUS-TBNA as a diagnostic tool for central intrapulmonary lesions adjacent to the trachea or the major bronchi is also well established. However, since the tip of the ultrasound probe at the distal end of the echobronchoscope is very thin, it can be wedged through smaller peripheral bronchi, reaching the distal parenchyma and allowing for peripheral pulmonary lesion sampling. The main aim of this retrospective study was to evaluate the diagnostic yield and the safety of EBUS-TBNA in the diagnosis of pulmonary peripheral nodules. The database of the Interventional Pulmonology Unit of Azienda Ospedaliero-Universitaria delle Marche (Ancona, Italy) was evaluated to identify peripheral pulmonary nodules approached by EBUS-TBNA. Thirty patients with a single peripheral pulmonary nodule located peripherally to the subsegmental bronchi of the lower lobes and adjacent to a small bronchus greater than 3 mm in diameter were included in this study. The nodule was visible using endoscopic ultrasound in 28 patients and the diagnosis was obtained via EBUS-TBNA in 26 cases (12 adenocarcinoma, 5 typical carcinoid tumors, 4 hamartoma and 5 metastatic lesions). The diagnostic yield was 86.6% for all 30 patients and 92.8% if only the 28 patients in which the lesion was visualized via echobronchoscopy were considered. No relevant adverse events were observed. We conclude that EBUS-TBNA may be an effective and safe option to sample pulmonary peripheral nodules in selected patients with lower lobe peripheral pulmonary lesions adjacent to small bronchi greater than 3 mm in diameter and reachable with the EBUS-TBNA probe.

Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database.

Introduction: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis. Methods: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis. Results: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09). Discussion: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.

Diagnostic Accuracy of Slow-Capillary Endobronchial Ultrasound Needle Aspiration in Determining PD-L1 Expression in Non-Small Cell Lung Cancer.

INTRODUCTION: The role of EBUS-TBNA in the diagnosis and staging of lung cancer is well established. EBUS-TBNA can be performed using different aspiration techniques. The most common aspiration technique is known as "suction". One alternative to the suction technique is the slow-pull capillary aspiration. To the best of our knowledge, no studies have assessed the diagnostic yield of slow-pull capillary EBUS-TBNA in PD-L1 amplification assessment in NSCLC. Herein, we conducted a single-centre retrospective study to establish the diagnostic yield of slow-pull capillary EBUS-TBNA in terms of PD-L1 in patients with NSCLC and hilar/mediastinal lymphadenopathies subsequent to NSCLC. MATERIALS AND METHODS: Patients with hilar and/or mediastinal lymph node (LN) NSCLC metastasis, diagnosed by EBUS-TBNA between January 2021 and April 2022 at Pulmonology Unit of "Ospedali Riuniti di Ancona" (Ancona, Italy) were enrolled. We evaluated patient characteristics, including demographic information, CT scan/ FDG-PET features and final histological diagnoses, including PD-L1 assessment. RESULTS: A total of 174 patients underwent EBUS-TBNA for diagnosis of hilar/mediastinal lymphadenopathies between January 2021 and April 2022 in the Interventional Pulmonology Unit of the "Ospedali Riuniti di Ancona". Slow-pull capillary aspiration was adopted in 60 patients (34.5%), and in 30/60 patients (50.0%) NSCLC was diagnosed. EBUS-TBNA with slow-pull capillary aspiration provided adequate sampling for molecular biology and PD-L1 testing in 96.7% of patients (29/30); in 15/29 (51.7%) samples with more than 1000 viable cells/HPF were identified, whereas in 14/29 (48.3%) samples contained 101-1000 viable cells/HPF. CONCLUSION: These retrospective study shows that slow-pull capillary aspiration carries an excellent diagnostic accuracy, almost equal to that one reported in literature, supporting its use in EBUS-TBNA for PD-L1 testing in NSCLC.

Case Report: Tracheal stenosis due to fibrotic bridges in a post-tracheostomy COVID-19 patient.

Tracheal stenosis is a common complication of prolonged endotracheal intubation or tracheostomy, that can be classified as simple (without cartilage involvement) or complex (with cartilaginous support involvement). We report a case of a post-COVID-19 tracheal stenosis with fibrotic bridges between the tracheal walls, creating a net within the lumen and causing significant respiratory distress. The absence of cartilaginous support involvement allowed a definitive bronchoscopic treatment with complete and permanent resolution of stenosis.

A lymph node mediastinal foreign body reaction mimicking nodal metastasis: A case series.

Introduction: In the last decades, many haemostatic substances included oxidized cellulose topically applied have been used during surgery and their use have become a common practice. Oxidized cellulose (OC) is one of the most used haemostatic substances. However, different studies have shown the persistence of OC deposits after surgical procedures that may simulate recurrent malignancies and abscesses. We present a case series of patients with enlarged on CT and PET-FDG positive lymphadenopathies due to foreign body inflammatory reaction to OC after lung surgery for pulmonary malignancies. Methods: Retrospective chart review of patients from 2021 to 2022 who underwent EBUS-TBNA for the characterization of hilar and/or mediastinal lymphadenopathies and a histopathological diagnosis of foreign body inflammatory reaction to OC. Results: Eight patients were referred to "Ospedali Riuniti di Ancona" (n = 7) and "Ospedale San Martino" (Genoa) (n = 1) Interventional Pulmonology Units for the characterization of hilar and/or mediastinal lymphadenopathies. All the evaluated patients underwent surgical procedures for lung cancers within the previous 12 months. EBUS-TBNA was performed in all the patients to rule out nodal metastasis. The cyto-pathological evaluation revealed amorphous acellular eosinofilic material surrounded by inflammatory reaction. As no other apparent causes might explain this finding and considering the temporal relationship between the lymphadenopathy and the lung surgery, foreign body inflammatory reaction to OC is the most likely cause of the phenomenon. Conclusion: In patients who underwent surgery for lung cancer, especially within few months, the development of lymph node foreign body reaction due to surgical material retention should always be considered.

Diagnostic Role of Bronchoalveolar Lavage in Patients with Suspected SARS-CoV-2 Pneumonia and Negative Upper Respiratory Tract Swab: A Systematic Review and Meta-Analysis.

The added role of bronchoalveolar lavage (BAL) in SARS-CoV-2 detection in hospitalized patients with suspected COVID-19 pneumonia and at least one negative nasopharyngeal swab (NPS) has yet to be definitively established. We aimed to provide a systematic review and meta-analysis to summarize data from the literature on the diagnostic yield of BAL in this context. We searched Medline and Embase for all studies reporting outcomes of interest published up to October 2021. Two authors reviewed all titles/abstracts and retrieved the selected full texts according to predefined selection criteria. The summary estimate was derived using the random-effects model. Thirteen original studies, involving 868 patients, were included. The summary estimate of proportions of SARS-CoV-2 positivity in BAL fluid in patients with at least one previous negative NPS was 20% (95% confidence interval [CI]; 11-30%). Moreover, microbiological tests of BAL fluid led to the identification of other pathogens, mainly bacteria, in up to two-thirds of cases. BAL plays a crucial role in the diagnostic work-up of patients with clinical suspicion of COVID-19 and previous negative NPS, as it allowed to detect the infection in a significant proportion of subjects, who would have been otherwise misclassified, with relevant implications in the prevention of disease spread, especially in hospital settings.

Suitability of transbronchial needle aspiration for genotyping peripheral pulmonary tumors.

Background: Transbronchial needle aspiration (TBNA) is a sampling tool that has demonstrated a higher accuracy in the diagnosis of peripheral pulmonary lesions (PPL) compared to other techniques. However, there are no studies investigating the value of TBNA in defining the genotype of peripheral lung cancer. Objective: To evaluate the accuracy of TBNA in defining the molecular characteristics of peripheral lung cancer. Methods: Consecutive patients who underwent TBNA for the diagnosis of a PPL at the Pulmonary Unit of the Azienda Ospedali Riuniti of Ancona (Italy) between January 2020 and September 2022 were included in the study. TBNA was performed under fluoroscopic guidance and the additional support of an ultrasound miniprobe, with an ultrathin bronchoscope with a flexible 21G needle. Samples were smeared on glass slides for cytological evaluation and flushed in 10% neutral-buffered formalin for cell-blocks. Results: 154 patients were enrolled:55 were diagnosed with adenocarcinoma and 21 with squamous cell carcinoma. TBNA correctly diagnosed 43/55 (78.2%) patients with adenocarcinoma and 17/21 (81.0%) patients with squamous cell carcinoma, with a sensitivity of 77.5%. Complete genotyping for guiding targeted therapies was obtained in 52 patients (86.6%). Conclusions: TBNA is a valid tool for the diagnosis of PPL, allowing a correct diagnosis and a complete genotyping of the tumors in a considerable proportion of patients.

Intrapleural Foreign Body: Case Report.

The detection of foreign bodies in the pleural cavity is rare and mostly consequent to iatrogenic or traumatic events. The migration of an inhaled foreign body from the airways to the pleural space through a bronchopleural fistula is an exceptional event. We report a case of a pleural empyema consequent to an inhaled wooden skewer. CT scan and bronchoscopy were unable to identify the foreign body, due to its migration in the peripheral airways. The thin and pointed foreign body perforated the visceral pleural surface emerging in the pleural cavity.

First Detection of SARS-CoV-2 by Real-Time Reverse Transcriptase-Polymerase Chain Reaction Assay in Pleural Fluid.

Coronavirus disease 2019 (COVID-19) is a pandemic infection due to the spread of a novel coronavirus (severe acute respiratory syndrome coronavirus 2), resulting in a wide range of clinical features, from asymptomatic carriers to ARDS. The gold standard for diagnosis is nucleic acid detection by real-time reverse transcriptase-polymerase chain reaction in nasopharyngeal swabs. However, due to limitations in this technique's sensitivity, thoracic imaging plays a crucial, complementary role in diagnostic evaluation and also allows for detection of atypical findings and potential alternative targets for sampling (eg, pleural effusion). Although less common, pleural involvement has been described in a minority of patients. This report describes the first case of reverse transcriptase-polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 in pleural fluid obtained by means of ultrasound-guided thoracentesis, and its main characteristics are detailed. Pleural effusion is not a common finding in COVID-19 infection, but a prompt recognition of this potential localization may be useful to optimize diagnostic evaluation as well as the management of these patients.