Design of the multicentre randomised controlled BENTO trial to demonstrate patient-relevant benefit of bronchoscopic lung volume reduction using thermal vapour ablation in the German healthcare system for patients with upper lobe emphysema: a study protocol.

INTRODUCTION: Application of vapour ablation as a novel approach to lung volume reduction has positive effects in patients with severe emphysema. The BENTO study is a randomised, controlled, open, multicentre trial, to assess the effects of bronchoscopic thermal vapour ablation (BTVA) in the German healthcare system. METHODS AND ANALYSIS: Patients with bilateral heterogeneous emphysema of the upper lobes in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3/4 will be enrolled in this trial and will receive either standard medical management alone (according to GOLD guidelines) or BTVA treatment with the InterVapor system together with standard medical management. Patients will be randomised in a 2:1 ratio (treatment group:control group). A total of 224 patients will be enrolled at 15 study sites. The primary endpoint is the change in patient-reported disease-specific quality of life, as measured by the St George's Respiratory Questionnaire for chronic obstructive pulmonary disease patients between randomisation and the 9-month follow-up visit. Secondary endpoints include adverse events, mortality, vital status, changes in lung function parameters, exercise capacity and other efficacy measures at 3, 9 and 12 months.The BENTO trial was commissioned by the German Federal Joint Committee, to demonstrate that this approach is an efficient and safe treatment option in the German healthcare system. ETHICS AND DISSEMINATION: The protocol has been approved by the lead ethics committee in Germany (Ethics Committee of the Medical Faculty of Heidelberg) and until present also by the following ethics committees: Ethics Committee of the Medical Faculty of Duisburg-Essen, Ethics Committee of the Medical Faculty of Martin-Luther-University Halle-Wittenberg, Ethics Committee of the State Medical Association of Hessen, Ethics Commission of the State Office for Health and Social Affairs of the State of Berlin, Ethics Committee of the Medical Faculty of Greifswald. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05717192.

Distinguishing bronchoscopically observed anatomical positions of airway under by convolutional neural network.

Background: Artificial intelligence (AI) technology has been used for finding lesions via gastrointestinal endoscopy. However, there were few AI-associated studies that discuss bronchoscopy. Objectives: To use convolutional neural network (CNN) to recognize the observed anatomical positions of the airway under bronchoscopy. Design: We designed the study by comparing the imaging data of patients undergoing bronchoscopy from March 2022 to October 2022 by using EfficientNet (one of the CNNs) and U-Net. Methods: Based on the inclusion and exclusion criteria, 1527 clear images of normal anatomical positions of the airways from 200 patients were used for training, and 475 clear images from 72 patients were utilized for validation. Further, 20 bronchoscopic videos of examination procedures in another 20 patients with normal airway structures were used to extract the bronchoscopic images of normal anatomical positions to evaluate the accuracy for the model. Finally, 21 respiratory doctors were enrolled for the test of recognizing corrected anatomical positions using the validating datasets. Results: In all, 1527 bronchoscopic images of 200 patients with nine anatomical positions of the airway, including carina, right main bronchus, right upper lobe bronchus, right intermediate bronchus, right middle lobe bronchus, right lower lobe bronchus, left main bronchus, left upper lobe bronchus, and left lower lobe bronchus, were used for supervised machine learning and training, and 475 clear bronchoscopic images of 72 patients were used for validation. The mean accuracy of recognizing these 9 positions was 91% (carina: 98%, right main bronchus: 98%, right intermediate bronchus: 90%, right upper lobe bronchus: 91%, right middle lobe bronchus 92%, right lower lobe bronchus: 83%, left main bronchus: 89%, left upper bronchus: 91%, left lower bronchus: 76%). The area under the curves for these nine positions were >0.98. In addition, the accuracy of extracting the images via the video by the trained model was 94.7%. We also conducted a deep learning study to segment 10 segment bronchi in right lung, and 8 segment bronchi in Left lung. Because of the problem of radial depth, only segment bronchi distributions below right upper bronchus and right middle bronchus could be correctly recognized. The accuracy of recognizing was 84.33 ± 7.52% by doctors receiving interventional pulmonology education in our hospital over 6 months. Conclusion: Our study proved that AI technology can be used to distinguish the normal anatomical positions of the airway, and the model we trained could extract the corrected images via the video to help standardize data collection and control quality.

Versatile workflow for cell type-resolved transcriptional and epigenetic profiles from cryopreserved human lung.

Complexity of lung microenvironment and changes in cellular composition during disease make it exceptionally hard to understand molecular mechanisms driving development of chronic lung diseases. Although recent advances in cell type-resolved approaches hold great promise for studying complex diseases, their implementation relies on local access to fresh tissue, as traditional tissue storage methods do not allow viable cell isolation. To overcome these hurdles, we developed a versatile workflow that allows storage of lung tissue with high viability, permits thorough sample quality check before cell isolation, and befits sequencing-based profiling. We demonstrate that cryopreservation enables isolation of multiple cell types from both healthy and diseased lungs. Basal cells from cryopreserved airways retain their differentiation ability, indicating that cellular identity is not altered by cryopreservation. Importantly, using RNA sequencing and EPIC Array, we show that gene expression and DNA methylation signatures are preserved upon cryopreservation, emphasizing the suitability of our workflow for omics profiling of lung cells. Moreover, we obtained high-quality single-cell RNA-sequencing data of cells from cryopreserved human lungs, demonstrating that cryopreservation empowers single-cell approaches. Overall, thanks to its simplicity, our workflow is well suited for prospective tissue collection by academic collaborators and biobanks, opening worldwide access to viable human tissue.

Age- and sex-dependent differences in patients with severe asthma included in the German Asthma Net cohort.

BACKGROUND: Severe asthma affects less than 5% of asthmatics, but is associated with high costs and increased mortality. The aim of this study was to assess age- and sex-dependent differences in this patient group. METHODS: Retrospective analysis of 1317 children and adults with severe asthma who are included in the German Asthma Net registry. RESULTS: There were more adults than children in the registry and patients' mean age was 52. Apart from children <18 years, there were more women (57%) than men. The age of first diagnosis ranged from 0 to 76 years. 38% of patients had a positive bronchial reversibility after short acting bronchodilators. Quality of life, FEV1 and MEF 25 decreased with older age whereas treatment with oral steroids and monoclonal antibodies increased. An anti-eosinophil treatment was most frequently used in patients aged around 57 years, while an anti-IgE treatment was used in all age-groups including children. There were sex-dependent differences with lower values in men for FEV1, FVC, MEF 25 and DLCO. Yet, women were more frequently unable to work than men due to the disease. CONCLUSION: In patients with severe asthma, clinical characteristics, but also treatments differed between age groups and between the sexes, reflecting different phenotypes of the disease.

Clinical and quantitative computed tomography predictors of response to endobronchial lung volume reduction therapy using coils.

Objectives: Bronchoscopic lung volume reduction using coils (LVRC) is a well-known treatment option for severe emphysema. The purpose of this study was to identify quantitative computed tomography (QCT) and clinical parameters associated with positive treatment outcome. Patients and methods: The CT scans, pulmonary function tests (PFT), and 6-minute walk test (6-MWT) data were collected from 72 patients with advanced emphysema prior to and at 3 months after LVRC treatment. The procedure involved placing 10 coils unilaterally. Various QCT parameters were derived using Apollo imaging software (VIDA). Independent predictors of clinically relevant outcome (Δ6-MWT ≥ 26 m, ΔFEV1 ≥ 12%, ΔRV ≥ 10%) were identified through stepwise linear regression analysis. Results: The response outcome for Δ6-MWT, for ΔFEV1 and for ΔRV was met by 55%, 32% and 42%, respectively. For Δ6-MWT ≥ 26 m a lower baseline 6-MWT (p = 0.0003) and a larger standard deviation (SD) of low attenuation cluster (LAC) sizes in peripheral regions of treated lung (p = 0.0037) were significantly associated with positive outcome. For ΔFEV1 ≥ 12%, lower baseline FEV1 (p = 0.02) and larger median LAC sizes in the central regions of treated lobe (p = 0.0018) were significant predictors of good response. For ΔRV ≥ 10% a greater baseline TLC (p = 0.0014) and a larger SD of LAC sizes in peripheral regions of treated lung (p = 0.007) tended to respond better. Conclusion: Patients with lower FEV1 and 6-MWT, with higher TLC and specific QCT characteristics responded more positively to LVRC treatment, suggesting a more targeted CT-based approach to patient selection could lead to greater efficacy in treatment response.

New bacterial growth in bronchial secretions after bronchoscopic valve implantation.

Background: Bronchoscopic valve implantation is an established treatment in selected patients with severe lung emphysema. There is evidence in literature of increased bacterial colonization of various implants. So far, it is unclear if an increased bacterial colonization can also be observed after endoscopic valve therapy. Methods: Retrospective analysis of patients with examination of the bronchial secretions for presence or change of bacterial growth before and after valve implantation. Results: Overall, 144 patients who underwent bronchoscopic follow-up after valve implantation were included in this analysis. Prior to valve placement, only 7 out of 144 consecutive emphysema patients (5%) presented with evidence of bacterial colonization, whereas 137 patients (95%) showed no bacterial growth prior to valve placement. One hundred seven out of the 137 patients (78%) showed new bacterial growth after valve implantation. Almost 38% of the patients who presented with a new bacterial growth had evidence of Viridans streptococci, Rothia mucilaginousa and Neisseria species simultaneously, as bacterial colonization. Pathogenic bacterial growth was recorded for Staphylococcus aureus (18%), Pseudomonas aeruginosa (13%) and Stenotrophomonas maltophilia (9%) microorganisms. There was also a significant bacterial growth by Moraxella catarrhalis (26%) and anaerobic bacteria (23%), especially in patients with complete atelectasis after successful endoscopic lung volume reduction. For all of the 7 patients, the presented initial bacterial colonization showed a change in the flora after bronchoscopy valve implantation. Conclusion: In this study we observed an increased bacterial colonization in the long term after valve implantation. This finding needs further evaluation regarding its possible clinical relevance but should be taken into consideration in the follow-up of these patients.

Coil therapy for patients with severe emphysema and bilateral incomplete fissures - effectiveness and complications after 1-year follow-up: a single-center experience.

BACKGROUND: Lung volume reduction coil (LVRC) treatment is established in daily endoscopic lung volume reduction routine. The aim of this study was to evaluate the safety and efficacy of LVRC treatment. PATIENTS AND METHODS: This was a retrospective analysis of 86 patients (male/female: 40/46, mean age: 64±7 years) with severe COPD and bilateral incomplete fissures. A total of 10 coils were unilaterally implanted in a single lobe, and 28 out of 86 patients were treated bilaterally. At 90-, 180-, and 365-day follow-up, changes in pulmonary function test (PFT), 6-minute walk test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale, as well as possible complications, were recorded. RESULTS: At 90 days, the forced expiratory volume in 1 second did improve (P<0.001), but the improvement was not sustained at the 180- and 365-day follow-up (baseline: 0.71±0.21 vs 0.77±0.23 vs 0.73±0.22 vs 0.70±0.18 L). Both vital capacity and residual volume improved significantly (P<0.001) at the 90- and 180-day follow-up, but the improvement was lost after 365 days. Total lung capacity decreased at the 90-day follow-up but returned to baseline values at the 180- and 365-day follow-up. 6MWT (P=0.01) and mMRC (P=0.007) also improved at 90 and 180 days (Δ6MWT of 31±54 and 20±60 m, respectively), but the improvement was also lost at the 365-day follow-up. No significant further improvement was evident at any point in the follow-up after the second procedure. A total of 4 out of 86 patients passed away due to complications. Significant complications in the first 3 months and then at 12 months included the following: severe hemoptysis in 4 (3.5%) and 4 (3.5%) patients, pneumonia requiring hospitalization in 32 (28.1%) and 9 (7.9%) patients and pneumothorax in 7 (6.1%) and 2 (1.7%) patients, respectively. Milder adverse events included self-limited hemoptysis, pneumonias, or COPD exacerbations treated orally. CONCLUSION: LVRC improved PFT, 6MWT and mMRC initially, but the improvement was lost after 365 days. Furthermore, we observed 4 deaths and significant severe complications, which need to be further elucidated.

Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema.

BACKGROUND: Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. METHODS: Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). FINDING: Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). INTERPRETATION: Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy.

Bronchoscopy in lung cancer: navigational modalities and their clinical use.

INTRODUCTION: More than 150,000 solitary pulmonary nodules are reported each year in the United States. As the popularity of low dose CT scan use for screening grows, these numbers are likely to increase substantially over the coming years. More than 10 million CT scans of the chest were performed in the United States alone in 2012, highlighting the potential for this clinical scenario. Detecting a nodule on either a chest radiograph or a CT scan frequently leads to a cascade of further investigations to establish a definite diagnosis. Thoracic surgery is frequently performed to obtain a tissue diagnosis in these cases, however, for what often turns out to be a benign abnormality. AREAS COVERED: During the last decade, several new technologies have been introduced to the field of bronchoscopy. As experience with these technologies has increased, the body of published literature has grown. Expert commentary: In this review, we assess the most important and interesting articles in the field. The value and the limitations of the various options will be discussed based on the actual evidence.

Technology update: bronchoscopic thermal vapor ablation for managing severe emphysema.

Bronchoscopic thermal vapor ablation (BTVA) is an endoscopic lung volume reduction therapy that presents an effective treatment approach in patients with severe upper lobe-predominant emphysema. By instillation of heated water vapor, an inflammatory reaction is induced, leading to fibrosis and scarring of the lung parenchyma, resulting in lobar volume reduction. Clinical single-arm trials demonstrated great outcomes, with significant improvement of lung function, exercise capacity, and quality of life. As the BTVA-induced local inflammatory response that seems to be essential for the desired lobar volume reduction can be associated with transient clinical worsening, strict monitoring of the patients is required. In future, the balance between efficacy and safety will constitute a major challenge. This review summarizes the BTVA procedure, the mechanism of action, and the results of the clinical trials, including the efficacy and safety data.

Treatment and outcome of patients with metastatic NSCLC: a retrospective institution analysis of 493 patients.

BACKGROUND: Most patients with metastatic non-small cell lung cancer (NSCLC) will face treatment with systemic therapy. Current clinical studies are demonstrating improvements in chemotherapy and overall survival. However, it remains unclear whether these results are translated into clinical practice. METHODS: We reviewed all stage IV NSCLC patients without second malignancies that were diagnosed from 2004 to 2006 at our institution. 493 consecutive patients were included into this retrospective analysis and were followed-up until end of 2011. RESULTS: 352 patients (71.4%) received systemic therapy for up to 7 lines. For most patients, adjustments of dosages or applications had to be made at some point of the treatment, but the total applied dose remained generally close to the intended dose. The best disease control (BDC) rate decreased with increasing therapy lines from 59.7% to about 35%. Patients with palliative local therapy but no systemic treatment demonstrated inferior survival (median 2.9 versus 8.7 months, p < 0.001). The median interval between last treatment and death was 50 days and 15 days for chemotherapy and anti-EGFR therapy, respectively. BDC to the previous therapy lines was predictive for improved BDC to third- but not second-line therapy. Performing multivariate analysis, BDC to previous therapy, never-/ former-smoking status, and age > 70 years were associated with improved survival performing third-line therapy. CONCLUSIONS: Stage IV NSCLC patients may receive substantial systemic therapy resulting in response and median survival rates that are comparable to data from clinical studies. However, preselection factors are increasingly important to improve therapy outcome and life quality.

From tissue to molecular phenotyping: pre-analytical requirements heidelberg experience.

Lung cancer is a leading cause of tumor-related death worldwide through years. Efforts to individualize lung cancer therapy to improve prognosis nowadays employ molecular analyses besides routine histopathological examination of tissue samples. In general, tissues are provided by bronchoscopy, CT-guided procedures or surgery. The sequence of tissue removal, storage, and processing has a considerable impact on the success and reliability of subsequent molecular biological analyses and will supposedly also influence therapeutic decisions. There is still an ongoing need for updated statements about the minimal requirements of tissue sampling for molecular diagnosis at international level and for certified/accredited quality control programs of the sampling procedures. Several of these issues may have to be adjusted to the individual local conditions. We will present several aspects of experiences gained in Thoraxklinik at the University Hospital of Heidelberg (TK-HD) with pre-analytical tissue requirements.

Endobronchial ultrasound.

Endobronchial ultrasound (EBUS) has emerged as a routinely performed procedure in diagnostic bronchoscopy. Extending the view beyond the airway wall, EBUS provides evaluation of tumor involvement of tracheobronchial wall and mediastinum and plays an essential role as a guidance technique for peripheral pulmonary diseases. The latest development is the EBUS-transbronchial needle aspiration (TBNA) scope that allows performing real-time EBUS-TBNA of enlargerd hilar and mediastinal lymph nodes.

Endoscopia respiratória no estadiamento do câncer de pulmão / Endoscopic staging of lung cancer

Câncer de pulmão é ainda a maior causa de mortalidade por câncer em todo mundo com uma pobre taxa de sobrevida. Acessar os linfonodos mediastinais são de fundamental importancia para um estadiamento adequado para definir a conduta terapêutica e o prognóstico. Um estadiamento adequado também é importante para melhorar as pesquisas para comparação de dados confiável. Novas técnicas diagnósticas tem ampliado a visão do broncoscopista e aumentado as possibilidadesde diagnóstico de processos mediastinais e do estadiamento do câncer de pulmão. Ultrassom endobrônquico e digestivo com punção aspirativa, navegação eletromagnética, auto fluorescência, tomografia de coerência ótica e microscopia confocal são alguns desses avanços que podem aumentar nossa capacidade de diagnosticar e estadiar o câncer de pulmão. Sem dúvida, implementação destas técnicas irão influenciar drasticamente os algoritmos para o diagnóstico e estadiamento em futuro próximo. Graças a esta abordagem minimamente invasiva, segura, acurada e de bom alcance diagnóstico, um completo estadiamento endoscópico ambulatorial pode ser o futuro.

Lung cancer is still the leading cause of cancer mortality worldwide with an overall poor survival rate. Mediastinal lymph node sampling in lung cancer is important for adequate staging in order to determine appropriate treatment as well as predicting outcome. Adequate staging of lung cancer is also important in order to improve research into lung cancer, for accurate comparison of data and for quality control. New diagnostic tools available have broadened the view of the bronchoscopist and augmented the diagnostic possibilities for mediastinal processes and staging of lung cancer. Endobronchial ultrasound and endoscopic ultrasound with needle aspiration, electromagnetic navigation, autofluorescence, coherence optical tomography and confocal microscopy are some of these new tools that can enhance our capability in diagnoseand staging accurately lung tumors. Beyond doubt, implementation of these techniques will drastically alter lung cancer diagnostic and staging algorithms in the near future. Thanks to its minimally invasive approach, safety record, accuracy and diagnostic reach, complete ambulant endoscopic staging of lung cancer might be the future.

A 65-year-old man with an endobronchial gossypiboma after lobectomy for abscessing pneumonia.

We present a case of a 65-year-old man with recurrent hemoptysis and weight loss for 6 months. Thirty-two years earlier, lobectomy of the right lower lobe had been performed for abcessing pneumonia. Due to recurrent pulmonary infections after lobectomy the patient had to retire at the age of 46. A diagnostic procedure to explain the hemoptysis was performed. A computed tomogram revealed a suspicious formation in the bronchus intermedius, and the patient was referred to our department with the suspicion of lung cancer. During bronchoscopy an endobronchial mass was detected and extracted whole with a foreign-body forceps. Textile fibers of a sponge in the histology specimen led to the final diagnosis of gossypiboma (also known as textiloma). After removal of the gossypiboma no further pulmonary infections occurred.

Electromagnetic navigation in lung cancer: research update.

Unfortunately, flexible bronchoscopy, the least invasive bronchoscopic procedure, is of limited value for obtaining tissue from lesions in the peripheral segments of the lung. Biopsy success is further compromised if the lesion is less than 3 cm in diameter. The main limitation of flexible bronchoscopy is the difficulty in reaching peripheral lesions with the accessory tools. In this paper, we will discuss a new bronchoscopic advance in the diagnosis and treatment of lung cancer. Once extended beyond the tip of the bronchoscope, these tools are difficult to guide to the desired location. Localizing the lesion under fluoroscopy is difficult, and alternative diagnostic guidance methods, such as computer tomography-guided bronchoscopy and endobronchial ultrasound, are more demanding. Therefore, new methods for navigation and localization are needed. One of these new technologies is electromagnetic navigation bronchoscopy. The aim of this special report is to provide an analysis of the published literature. A literature search was constructed and performed on PubMed to identify the literature from 2000 to 2008. The search words were 'electromagnetic navigation', 'coin lesion', 'solitary pulmonary nodule' and 'lung cancer'. We review a number of recent studies that utilize electromagnetic navigation and guidance, and analyze their performance characteristics for clinical applications of the technology. Electromagnetic navigation is likely to play an increasing and integral role in the diagnosis and staging of lung cancer in the near future. Electromagnetic registration may impact both the staging and diagnosis of peripheral lesions.

Endobronchial ultrasound and electromagnetic navigation bronchoscopy in the diagnosis of peripheral lung lesions.

BACKGROUND: Unfortunately, flexible bronchoscopy, the least invasive bronchoscopic procedure, is of limited value for obtaining tissue from lesions in the peripheral segments of the lung. Biopsy success is compromised further if the lesion is < 2 cm in diameter. The main limitation of flexible bronchoscopy is the difficulty in reaching peripheral lesions with the accessory tools. OBJECTIVE: Once extended beyond the tip of the bronchoscope, these tools are difficult to guide to the desired location. Localizing the lesion under fluoroscopy is difficult, and alternative diagnostic guidance methods, such as computer tomography-guided bronchoscopy and endobronchial ultrasound, are more demanding. Therefore, new methods for navigation and localization are needed. One of these new technologies is the use of endobronchial ultrasound miniprobes followed by a guided biopsy. The other is electromagnetic navigation bronchoscopy. METHOD: The aim of the systematic review is to provide an analysis of the published literature. RESULTS/CONCLUSION: Both systems showed an increased yield in diagnosing solitary pulmonary nodules. The body of evidence is growing rapidly. The ultimate goal of reliable and minimally invasive biopsy of peripheral lung lesions now appears feasible.