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Judith Maria Brock,1,2 Paul Ulrich Schuster,3 Felix Böhmker,3 Ralf Eberhardt,4 Daniela Gompelmann,5 Konstantina Kontogianni,1,2 Franziska Trudzinski,1,2 Nicola Benjamin,1 Felix Herth1,2 1Department of Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, Germany; 2Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany; 3Medical Faculty, University of Heidelberg, Heidelberg, Germany; 4Department of Pneumology and Intensive Care Medicine, Asklepios Klinik Barmbek, Hamburg, Germany; 5Department of Internal Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, AustriaCorrespondence: Judith Maria Brock, Department of Pneumology and Critical Care Medicine, Thoraxklinik Heidelberg, University Hospital of Heidelberg, Röntgenstraße 1, Heidelberg, 69126, Germany, Tel +49 6221-3968256, Email Judith.Brock@med.uni-heidelberg.dePurpose: Up to 41% of patients with endobronchial valve implantation need revision bronchoscopies and valve replacements most likely due to valve dysfunction or lack of benefit. So far, no data is available whether valve replacements lead to the desired lobar volume reduction and therapy benefit.Patients and Methods: We conducted a single-center retrospective analysis of patients with endobronchial valve implantation and at least one valve replacement. Indications and number of revision bronchoscopies and valve replacements were evaluated. Therapy benefit regarding lung function and exercise capacity as well as development of complete lobar atelectasis was investigated and possible predictors identified.Results: We identified 73 patients with 1– 12 revision bronchoscopies and 1– 5 valve replacements. The main indication for revision bronchoscopy in this group was lack of therapy benefit (44.2%). Lung function and exercise capacity showed improvements in about one-third of patients even years after the initial implantation. A total of 26% of all patients showed a complete lobar atelectasis at the end of the observation period, 56.2% had developed lung volume reduction. The logistic regression revealed the development of a previous complete lobar atelectasis as predictor for a complete lobar atelectasis at final follow-up. Oral cortisone long-term therapy was also shown as predictive factor. The probability for a final complete lobar atelectasis was 69.2% if a lobar atelectasis had developed before.Conclusion: Valve replacements are more likely to be beneficial in patients who develop a re-aeration of a previous lobar atelectasis following valve implantation. Every decision for revision bronchoscopy must be taken carefully.Keywords: endobronchial lung volume reduction, endobronchial valves, valve replacement, revision bronchoscopy, COPD

Markus Polke,1 Jonas Brugger,2 Matthias Rötting,3 Nilab Polke,1 Judith Brock,1 Stefanie Schuler,1 Ines Richter,1 Ralf Eberhardt,1,4,5 Felix JF Herth,1,5 Daniela Gompelmann1,5,6 1Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, Germany; 2Institute for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria; 3Medizinische Klinik V, Klinikum Fulda, Fulda, Deutschland; 4Pneumologie & Internistische Intensivmedizin, Asklepios Klinik Barmbek, Hamburg, Deutschland; 5Translational Lung Research Center Heidelberg (TLRCH, German Center for Lung Research (DZL), Heidelberg, Germany; 6Department of Internal Medicine II, Division of Pulmonology, Medical University of Vienna, Vienna, AustriaCorrespondence: Markus Polke, Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, Germany, Email markus.polke@med.uni-heidelberg.deAims and Objectives: Many patients with chronic obstructive lung disease suffer from emphysema. Valve implantation may be a reasonable method in patients presenting advanced emphysema and absent interlobar collateral ventilation (CV). However, other clinical parameters influencing the effectiveness of endoscopic lung volume reduction (ELVR) are not well known.Methods: COPD patients with advanced emphysema who received valve implantation in 2016 were retrospectively analyzed. The following characteristics were collected prior to valve implantation: age, sex, body mass index, presence of allergies, use of inhaled corticosteroids (ICS), lung function parameters, diffusion capacity, 6-minute walk distance (6-MWD), blood gases, COHb, smoking history, and emphysema index (quantitative multi-detector computed tomography). Three months following valve implantation, lung function parameters, diffusion capacity, 6-MWD and blood gases were measured. In this analysis, we evaluated the impact of these variables on an increase in FEV1 and 6-MWT as well as a decrease in RV three months after valve implantation.Results: Overall, 77 COPD patients (57% male, mean age 66, mean FEV1 32%, mean RV 259%) who underwent valve therapy were enrolled. At 3-month follow-up, patients experienced a mean FEV1 increase of 0.09 ± 0.21 L, a mean RV decrease of 0.42 ± 1.80 L and a mean improvement of 8.3 ± 57 m in the 6-MWT. Overall, ICS, sex and emphysema index had an impact on the outcome following ELVR: ICS medication was associated with inferior FEV1 outcome. The higher the emphysema index, the less the RV reduction. Sex was a predictor for change of FEV1 (%), RV (L), and 6-MWT: male patients seem to benefit less than female patients from valve implantation.Conclusion: These findings suggest that ICS, emphysema index and sex are clinical parameters that may be associated with inferior outcome following ELVR. Further studies have to confirm these results to improve patient selection and clinical outcome of ELVR.Keywords: COPD, emphysema, valve implantation, lung volume reduction

Konstantina Kontogianni,1,2 Kanoe Russell,3 Ralf Eberhardt,1,2 Maren Schuhmann,1,2 Claus Peter Heussel,2,4 Susan Wood,3 Felix JF Herth,1,2 Daniela Gompelmann1,2 1Department of Pulmonology and Respiratory Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany; 2Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research DZL, Heidelberg, Germany; 3VIDA Diagnostics, Coralville, IA, USA; 4Diagnostic and Interventional Radiology with Nuclear Medicine, Chest Clinic (Thoraxklinik), University of Heidelberg, Heidelberg, Germany 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 (∆6-MWT ≥ 26 m, ∆FEV1 ≥ 12%, ∆RV ≥ 10%) were identified through stepwise linear regression analysis.Results: The response outcome for ∆6-MWT, for ∆FEV1 and for ∆RV was met by 55%, 32% and 42%, respectively. For ∆6-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 ∆FEV1 ≥ 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 ∆RV ≥ 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. Keywords: COPD, emphysema, interventional pulmonology, bronchoscopy, endoscopic lung volume reduction, endobronchial coils

Nilab Sarmand,1 Daniela Gompelmann,1,2 Konstantina Kontogianni,1 Markus Polke,1 Felix JF Herth,1,2 Ralf Eberhardt1,2 1Department of Pulmonology and Respiratory Care Medicine, Thoraxklinik, at the University of Heidelberg, Heidelberg, ²Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research DZL, at the University of Heidelberg, Heidelberg, Germany 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. Keywords: valve implantation, lung volume reduction, bacterial growth, COPD

D Gompelmann,1,2 K Kontogianni,1 M Schuhmann,1 R Eberhardt,1,2 CP Heussel,2–4 FJ Herth1,2 1Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, 2Translational Lung Research Center Heidelberg (TLRCH), German Center for Lung Research, Heidelberg (DZL), 3Diagnostic and Interventional Radiology, Thoraxklinik at University of Heidelberg, Heidelberg, 4Diagnostic and Interventional Radiology at University of Heidelberg, Heidelberg, Germany Objective: Endoscopic valve therapy aims at target lobe volume reduction (TLVR) that is associated with improved lung function, exercise tolerance and quality of life in emphysema patients. So far, a TLVR of >350 mL was considered to be indicative of a positive response to treatment. However, it is not really known what amount of TLVR is crucial following valve implantation. Patients and methods: TLVR, forced expiratory volume in 1 second (FEV1), residual volume (RV) and 6-minute walk distance (6-MWD) were assessed before and 3 months after valve implantation in 119 patients. TLVR was calculated based on computed tomography (CT) scan analysis using imaging software (Apollo; VIDA Diagnostics). Minimal important difference estimates were calculated by anchor-based and distribution-based methods. Results: Patients treated with valves experienced a mean change of 0.11 L in FEV1, -0.51 L in RV, 44 m in 6-MWD and a TLVR of 945 mL. Using a linear regression and receiver operating characteristic analysis based on two of three anchors (ΔFEV1, ΔRV), the estimated minimal impor­tant difference for TLVR was between 890 and 1,070 mL (ie, 49%–54% of the baseline TLV). Conclusion: In future, a TLVR between 49% and 54% of the baseline TLV, should be used when interpreting the clinical relevance. Keywords: emphysema, hyperinflation, target lobe volume reduction

Konstantina Kontogianni,1,2 Vasiliki Gerovasili,3 Daniela Gompelmann,1,2 Maren Schuhmann,1,2 Hans Hoffmann,2,4 Claus Peter Heussel,2,5 Felix JF Herth,1,2 Ralf Eberhardt1,2 1Department of Pulmonology and Respiratory Care Medicine, Thoraxklinik at the University of Heidelberg, 2Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research DZL, Heidelberg, Germany; 3Department of Respiratory Medicine, Harefield Hospital, Royal Brompton & Harefield NHS Foundation Trust, London, UK; 4Department of Thoracic Surgery, Thoraxklinik at the University of Heidelberg, 5Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany 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

D Gompelmann,1,2 N Benjamin,1 K Kontogianni,1 FJF Herth,1,2 CP Heussel,2–4 H Hoffmann,2,5 R Eberhardt1,2 1Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, 2German Center for Lung Research, 3Diagnostic and Interventional Radiology, Thoraxklinik at University of Heidelberg, 4Diagnostic and Interventional Radiology, University Hospital Heidelberg, 5Thoracic Surgery, Thoraxklinik at University of Heidelberg, Heidelberg, Germany Introduction: Valve implantation has evolved as a therapy for patients with advanced emphysema. Although it is a minimally invasive treatment, it is associated with complications, the most common being pneumothorax. Pneumothorax occurs due to the rapid target lobe volume reduction and may be a predictor of clinical benefit despite this complication. Objective: The objective of this study was to conduct an exploratory data analysis of patients who developed a pneumothorax following endoscopic valve therapy for emphysema. Materials and methods: This study performed a retrospective evaluation of pneumothorax management and the impact of pneumothorax on clinical outcomes in 70 patients following valve therapy in 381 consecutive patients. Results: Pneumothorax rate following valve therapy was 18%. Pneumothorax management consisted of chest tube insertion, valve removal, and surgical intervention in 87% (61/70), 44% (31/70), and 19% (13/70) of the patients, respectively. Despite pneumothorax, patients experienced modest but significant improvements in lung function parameters (forced expiratory volume in 1 second: 55±148 mL, residual volume: -390±964 mL, total lung capacity: -348±876; all P

Daniela Gompelmann,1,2,* Hyun-ju Lim,3,4,* Ralf Eberhardt,1,2 Vasiliki Gerovasili,5 Felix JF Herth,1,2 Claus Peter Heussel,2–4 Monika Eichinger3,4 1Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, 2Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, 3Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, 4Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany; 5First Critical Care Department, National and Kapodistrian University of Athens, Athens, Greece *These authors contributed equally to this work 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. Keywords: endoscopic lung volume reduction, COPD, emphysema, pneumothorax, valve therapy

Ralf Eberhardt,1,2 Daniela Gompelmann,1,2 Felix JF Herth,1,2 Maren Schuhmann1 1Pneumology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, 2Translational Lung Research Center, Member of the German Center for Lung Research, Heidelberg, Germany Abstract: As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are available to achieve lung volume reduction in patients with severe emphysema and significant hyperinflation. Lung function parameters and comorbidities of the patient, as well as the extent and distribution of the emphysema are factors to be considered when choosing the patient and the intervention. Endoscopic bronchial valve placement with complete occlusion of one lobe in patients with heterogeneous emphysema is the preferred technique because of its reversibility. The presence of high interlobar collateral ventilation will hinder successful treatment; therefore, endoscopic coil placement, polymeric lung volume reduction, or bronchoscopic thermal vapor ablation as well as lung volume reduction surgery can be used for treating patients with incomplete fissures. The effect of endoscopic lung volume reduction in patients with a homogeneous distribution of emphysema is still unclear and this subgroup should be treated only in clinical trials. Precise patient selection is necessary for interventions and to improve the outcome and reduce the risk and possible complications. Therefore, the patients should be discussed in a multidisciplinary approach prior to determining the most appropriate treatment for lung volume reduction. Keywords: lung emphysema, valve treatment, collateral ventilation, patient selection, outcome

Daniela Gompelmann,1,2 Ralf Eberhardt,1,2 Felix JF Herth1,21Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, 2German Center for Lung Research, Heidelberg, GermanyAbstract: 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.Keywords: emphysema, bronchoscopy, bronchoscopic thermal vapor ablation