[EBUS-guided cryobiopsy in the diagnosis of mediastinal lesions - step by step]. / EBUS-gestützte Kryobiopsie mediastinaler Läsionen ­ Schritt für Schritt.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the gold standard in the diagnosis of mediastinal and hilar lesions. For certain purposes, such as the diagnosis and subtyping of lymphoproliferative disorders or molecular pathology, a larger amount of intact sample material is required. EBUS cryobiopsy is a new and efficient tool for this purpose. As it is a new approach, there is still no standardised workflow. In this review, we present the procedure step by step as it is performed at the Ruhrlandklinik in Essen.

Impact of Bronchoscopic Lung Volume Reduction with Valves on the Pulmonary Gas Exchange.

Introduction: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves has been shown to be a safe and effective treatment for patients with severe lung emphysema. Previous studies have reported a benefit in pulmonary function, exercise capacity, and quality of life after BLVR-treatment. The effect of BLVR with valves on the pulmonary gas exchange and its association with clinical outcomes has not been analyzed to date. The primary goal of this study was to investigate the impact of BLVR on the pulmonary gas exchange and the impact of the target lobe selection in patients with discordant target lobes in high-resolution computed tomography (HRCT) scan and perfusion scan on the pulmonary gas exchange and clinical outcomes. Methods: In this single-center study, we retrospectively analyzed pulmonary function tests, 6-min-walk-tests, HRCT scans, perfusion scans, and blood gas analyses in 77 patients over the course of 6 months following BLVR treatment. Results: We observed that complete lobar occlusion with bronchoscopic valves leads to a transient impairment of pulmonary gas exchange. Despite this, an overall positive clinical outcome could be shown in patients treated with endobronchial valves. If the target lobe selection based on HRCT and perfusion scans is discrepant, a selection based on the HRCT scan tends to be associated with a better outcome than a selection based on the perfusion scan. Conclusions: Complete lobar occlusion with bronchoscopic valves leads to a transient impairment of pulmonary gas exchange but nevertheless results in an overall positive clinical outcome.

Predictive value of Chartis measurement for lung function improvements in bronchoscopic lung volume reduction.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) via valve implantation can be achieved by targeting severely hyperinflated and emphysematously destructed lung areas in patients with chronic obstructive lung disease. Lack of collateral ventilation (CV) is important for good outcomes with BLVR. CV can be measured using the catheter-based Chartis system. The aim of this study was to evaluate the correlation between total exhaled volume drained from the target lobe measured by Chartis and clinical outcomes after BLVR in CV-negative patients. METHODS: From January 2016 to March 2019, 60 patients were included in this retrospective single-center analysis. Drained volume (TVol) measured by Chartis was recorded and compared with lung function and physical performance parameters. Outcome variables included the percentage change in lung function [forced expiratory volume in 1 s (FEV1), residual volume (RV), and inspiratory vital capacity (IVC)]. Secondary outcomes were the degree of target lobe volume reduction (TLVR), change in 6-min walk distance (6MWD), and change in chronic obstructive pulmonary disease (COPD) assessment test (CAT) score. RESULTS: Drained volume correlated significantly with post-BLVR change in FEV1 (r = 0.663), IVC (r = 0.611), RV (r = -0.368), and TLVR (r = 0.635) (all p < 0.05). In a priori-defined patient subgroups based on drained volume [<100 ml (n = 19), 100-400 ml (n = 33), and >400 ml (n = 8)]; mean changes in FEV1 were 2.6%, 17.4%, and 51.3%; in RV were -3.9%, -10.6%, and -23.8%; in IVC were -4.0%, 10.6%, and 62.4%; and in TLVR were 525 ml (39%), 1375 ml (73%) and 1760 ml (100%), respectively. There were no significant correlations between absolute and percentage changes in 6MWD and the CAT score. Lung volume reduction was diagnosed in 32 (53%) cases. CONCLUSION: Drained volume measured by the Chartis system correlated with functional improvement in CV-negative patients undergoing BLVR. The reviews of this paper are available via the supplemental material section.

Thoracic Ultrasound for Immediate Exclusion of Pneumothorax after Interventional Bronchoscopy.

BACKGROUND: Pneumothorax is a common side effect in interventional pulmonology. The ideal moment for detection with chest X-ray or ultrasound has not yet been defined. Earlier studies demonstrated the utility of performing these tests with a certain delay, which always results in a potentially dangerous gap. METHODS: We prospectively enrolled patients with pulmonary interventions at increased risk of pneumothorax. Thoracic ultrasound was performed immediately after the intervention and at the moment of chest X-ray with a delay up to two hours. RESULTS: Overall, we detected four pneumothoraxes in 115 procedures. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 75%, 100%, 100%, 99%, 99% for ultrasound and 75%, 90%, 21%, 99% und 89% for chest X-ray respectively. All pneumothoraces requiring chest tube were sufficiently detected by both methods. CONCLUSION: Thoracic ultrasound when performed immediately can more accurately exclude pneumothorax after interventional bronchoscopy when compared to chest X-ray. Further ultrasound examinations are unnecessary.

Integration of Bronchoscopic Transesophageal Ultrasound Examination of the Left Adrenal Gland into Routine Lung Cancer Staging Workup: A Prospective Trial.

BACKGROUND: Endobronchial ultrasound (EBUS) with transbronchial needle aspiration increases the diagnostic yield of lung cancer staging. The left adrenal gland (LAG) is a common site for lung cancer metastasis. The modality of transesophageal examination with an EBUS bronchoscope (EUS-B) routinely for LAG has not been assessed. OBJECTIVE: The aim of this study was to prospectively assess if evaluation and tissue sampling of the LAG could routinely be implemented in an EBUS procedure. METHODS: Patients referred for EBUS between March and August 2017 had assessment of the LAG via EUS-B. Fine-needle aspiration (FNA) was performed in cases with a suspicious LAG. The detection rate, procedure time, and learning curve of four experienced EBUS-bronchoscopists was assessed, plus the diagnostic accuracy and complication rate of FNA. RESULTS: In total, 313 consecutive patients were included. The overall LAG detection rate was 87.5%. After the initial learning curve, the detection rate for all four bronchoscopists was >93%. The detection rate did not correlate with any patient characteristics. EUS-B-FNA revealed nine LAG metastases, with a sensitivity, specificity, and accuracy of 75%, 100%, and 99%, respectively. The mean EUS-B operation time was 194.4 s, with 594.8 s for FNA. There were no FNA-associated complications. CONCLUSIONS: Evaluation of the LAG with EUS-B could routinely be included in an EBUS procedure if necessary. A high detection rate can be achieved after an initial learning period. FNA of the LAG was feasible and safe. EUS-B of the LAG could be integrated into the usual EBUS/EUS-B procedure in lung cancer staging workup.

Bronchial Thermoplasty Including the Middle Lobe Bronchus Significantly Improves Lung Function and Quality of Life in Patients Suffering from Severe Asthma.

PURPOSE: Bronchial Thermoplasty (BT) is indicated in patients suffering from severe and symptomatic bronchial asthma despite maximal medical therapy. However, treatment of the right middle lobe (RML) bronchus is currently not recommended. The aim of this study was to investigate the safety and efficacy of BT if the RML bronchus is included. METHODS: BT was performed in 17 consecutive patients, quality of life and pulmonary function were characterized before and 90 days after BT completion. Furthermore, we performed a clean-up bronchoscopy following every BT. This study was approved by the IRB of the University of Essen (No. 17-7356 BO) and registered as a retrospective observational study at the German Clinical Trials Registry (No. DRKS 00011550). RESULTS: The median baseline values of FEV1 and Asthma Questionnaire of Life Quality (AQLQ) were 1.33 l (0.91; 1.73) and 3.01 (2.76; 3.61), respectively, and significantly improved 90 days after treatment with FEV 1 at 1.75 l (p-value 0.002) and AQLQ 3.8 (p-value < 0.05). Also the amount of oral corticosteroid necessity decreased significantly. No severe adverse events occurred due to the procedure. Clean-up bronchoscopies-when performed-revealed significant fibrinous exudation after every BT procedure. CONCLUSION: BT including the RML bronchus is feasible. Functionally limited patients with severe asthma could potentially profit. Due to the relevant fibrinous exudation, BT should be followed by clean-up bronchoscopy, not only after RML treatment.

Towards Individualized Tracheobronchial Stents: Technical, Practical and Legal Considerations.

Stent placement has been established as a standard procedure for treating airway obstructions. Other indications are localized malacias and fistulas. Though many different stents with various diameters and lengths are available, the shapes are hardly ever ideal because of the distorted anatomy in patients with diseased airways. There are technical and legal limitations for customizing purchased airway stents. Individually tailored stents would be preferable. New techniques of additive manufacturing such as 3D printing make it possible to produce optimized stents for a particular patient. Using CT data and bronchoscopic images, stents can be constructed that match a particular anatomical situation and apply the optimized expansion force. We give an overview of the currently available manufacturing techniques for polymeric stents and report about our own experience. Direct on-site printing of polyurethane stents in a hospital and printing individual extrusion molds for silicone stents in a certified cleanroom are both feasible. Furthermore, there are promising attempts of combining mechanically customized stents with surface modifications, drug-eluting features, biodegradability, and time-dependent adaptation (4D printing). Truly optimized airway stents with the potential of solving the well-known stent problems such as granulation tissue formation, remodeling, mucostasis, and infections are in reach. The technical hurdles are probably easier to overcome than the legal constraints. The legal situations are discussed from a physician's and a manufacturer's perspective.

Oxidation of cofilin mediates T cell hyporesponsiveness under oxidative stress conditions.

Oxidative stress leads to impaired T cell activation. A central integrator of T cell activation is the actin-remodelling protein cofilin. Cofilin is activated through dephosphorylation at Ser3. Activated cofilin enables actin dynamics through severing and depolymerization of F-actin. Binding of cofilin to actin is required for formation of the immune synapse and T cell activation. Here, we showed that oxidatively stressed human T cells were impaired in chemotaxis- and costimulation-induced F-actin modulation. Although cofilin was dephosphorylated, steady-state F-actin levels increased under oxidative stress conditions. Mass spectrometry revealed that cofilin itself was a target for oxidation. Cofilin oxidation induced formation of an intramolecular disulfide bridge and loss of its Ser3 phosphorylation. Importantly, dephosphorylated oxidized cofilin, although still able to bind to F-actin, did not mediate F-actin depolymerization. Impairing actin dynamics through oxidation of cofilin provides a molecular explanation for the T cell hyporesponsiveness caused by oxidative stress.