Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex. METHODS: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and immunoaffinity-purified anti-PDGFRα antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

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.

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.

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.

Immunohistochemistry for Claudin-4 and BAP1 in the Differential Diagnosis between Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41/41 SMs, while it was positive in 18/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23/41 SMs, while it was regularly expressed in 46/46 SCs. All the cases of the normal/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM.

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.

Efficacy of Small versus Large-Bore Chest Drain in Pleural Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural infection represents a significant clinical challenge worldwide. Although prompt drainage of pleural fluid is thought to play a key role in pleural infection management, the optimal size of intrapleural catheter has yet to be defined. OBJECTIVES: The aim of this systematic review and meta-analysis was to summarize data on efficacy and complications of small-bore drain (SBD), defined as ≤14F, in comparison to large-bore drain (LBD) in patients with pleural infection. METHOD: We searched MEDLINE and Embase for all studies reporting outcomes of interest published up to October 2021. Two authors reviewed selected full text to identify studies according to predefined eligibility criteria. Summary estimates were derived using the random-effects model. RESULTS: Twelve original studies were included for qualitative analysis and 7 of these for quantitative analysis. The surgical referral rate of SBD and LBD were, respectively, 0.16 (95% confidence interval [CI], 0.12-0.21) and 0.20 (95% CI, 0.10-0.32), the pooled mortality were 0.12 (95% CI, 0.05-0.21) and 0.20 (95% CI, 0.10-0.32), and the length of hospital stay was 24 days in both groups. Data on complications suggest similar proportions of tube dislodgement. Intensity of pain was evaluated in one study only, reporting higher scores for LBD. CONCLUSIONS: This systematic review and meta-analysis provide the first synthesis of data on performance of SBD and LBD in management of pleural infection, and, overall, clinical outcomes and complications did not substantially differ, although the limited number of studies and the absence of dedicated randomized trials does limit the reliability of results.

Historical eye: from traditional to endobronchial ultrasound-guided needle aspiration and beyond.

PURPOSE OF REVIEW: In the history of bronchoscopy, the advent of flexible transbronchial needle aspiration (TBNA) before and, subsequently, of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), have represented fundamental events, as they have significantly and definitively changed interventional pulmonology's role in diagnostic and therapeutic work-up of most of thoracic diseases.Purpose of this historical review is to retrace the main stages that have contributed to the development of these two techniques. RECENT FINDINGS: TBNA allowed the bronchoscopists to overcome the barrier of the tracheobronchial wall and to obtain samples from hilar-mediastinal lesions. With this additional method, bronchoscopy has become an essential procedure for staging of lung cancer.The advent of echo-bronchoscopes, allowing to perform TBNA under direct ultrasound guidance in real time, further increased the diagnostic yield of this technique. Furthermore, the insertion of the echo-bronchoscope through the oesophagus allowed to extend the landscape of targets to sample, including also para-esophageal lesions, liver metastases, celiac nodes and left adrenal glands.EBUS-TBNA has shown its usefulness not only in the approach to mediastinal lesions, but also in other clinical conditions, such as lung nodules or masses adjacent to the tracheobronchial tree. SUMMARY: Despite the obvious advantages of EBUS-TBNA, this technology is not yet available in many centres and countries worldwide. For this reason, TBNA remains a basic technique that must complete the technical background of bronchoscopists and it should not be forgotten.

Validation of a Cytological Classification System for the Rapid On-Site Evaluation (Rose) of Pulmonary and Mediastinal Needle Aspirates.

Rapid on-site evaluation (ROSE) is a procedure that allows immediate assessment of adequacy of cytological specimens obtained by fine needle aspiration (FNA). The application of ROSE diagnostic categories has been applied in various organs, but not in thoracic pathology. We aimed to retrospectively assess the concordance with the final diagnosis of a categorization from C1 (inadequate) to C5 (neoplastic) during ROSE performed with bronchoscopic or percutaneous sampling procedures of thoracic lesions in a large series of consecutive cases. This retrospective single-center study evaluated 2282 consecutive ROSEs performed on 1827 patients from January 2016 to December 2020 in 994 cases of transbronchial needle aspiration (TBNA) in peripheral pulmonary lesions, in 898 transthoracic FNAs, in 318 ultrasound-guided TBNAs, in 50 conventional TBNAs and in 22 endobronchial TBNAs. False positive and false negative cases of ROSE were 43 (1.88%) and 73 (3.2%), respectively, when compared with the definitive diagnosis. The sensitivity, specificity and the positive and negative prognostic values of ROSE were 94.84%, 95.05%, 96.89% and 91.87%, respectively. Overall concordance between ROSE and the final diagnosis was 0.8960 (Cohen's kappa). No significant differences were observed in terms of sampling procedures and type and location of the lesions. A tiered classification scheme of ROSE from C1 to C5 during bronchoscopic and percutaneous sampling procedures is helpful in effectively guiding clinical management of patients with thoracic lesions.

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.

Predictors of Malignancy in Patients With Haemoptysis

No disponible

Accuracy and Predictors of Success of EUS-B-FNA in the Diagnosis of Pulmonary Malignant Lesions: A Prospective Multicenter Italian Study.

BACKGROUND: The role of endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) in the diagnosis of suspected malignant pulmonary lesions adjacent to the esophagus has been poorly investigated. The aim of the present study was to assess the accuracy of EUS-B-FNA for the diagnosis and molecular profiling of paraesophageal pulmonary lesions, as well as its predictors of success. MATERIALS AND METHODS: Patients who underwent EUS-B-FNA for the diagnosis of paraesophageal lesions were consecutively enrolled in four Italian centers. Demographic, clinical, procedural, pathological, and molecular characteristics of the malignant samples were collected. The primary outcome was the diagnostic accuracy for pulmonary malignancies. Secondary outcomes were diagnostic yield and predictors of success for diagnosis and molecular profiling. RESULTS: 107 adult patients (60 [56.1%] males; median (interquartile range) age: 69 [60-70] years) were enrolled. The diagnostic accuracy of EUS-B-FNA was 95.3% in the overall cohort and 95.2% in the 99 patients with a final diagnosis of malignancy. Neither clinical nor procedural variables significantly affected the diagnostic accuracy, whereas rapid on-site evaluation (ROSE), performed by pathologists or trained pulmonologists, was a strong predictor for a complete molecular profiling (OR [95% CI]: 12.9 [1.2-137.4]; p value: 0.03). CONCLUSION: EUS-B-FNA is a safe and accurate method for the diagnosis of paraesophageal pulmonary lesions. The presence of ROSE is relevant for a complete molecular profiling in this selected cohort of patients with advanced lung cancer.

Bronchoscopic diagnosis of peripheral lung lesions.

PURPOSE OF REVIEW: Over the last decades, in addition to the traditional fluoroscopy, various and innovative guidance systems have been adopted in clinical practice for transbronchial approach to peripheral pulmonary lesions (PPLs). The aim of this article is to summarize the most recent data on available guidance systems and sampling tools, evaluating also advantages and limitations of each technique. RECENT FINDINGS: Although several studies have been published over the last years, large randomized studies comparing the different techniques are scanty. Fluoroscopy is the traditional and still most widely utilized guidance system. New guidance systems (electromagnetic navigation bronchoscopy, ultrasound miniprobe, cone beam computed tomography) seems to provide a better sensitivity, especially for small lesions not visualized by fluoroscopy. Among the sampling instruments, there is a good evidence that flexible transbronchial needle provides the better diagnostic yield and that sensitivity may increase if more than one sampling instrument is used. SUMMARY: Even if great progress has been done since the first articles on the transbronchial approach to PPLs, better scientific evidence and more reliable randomized trials are needed to guide interventional pulmonologists in choosing the best technique according to different clinical scenarios and source availability.

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.