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Nora Drick,1,* Katrin Milger,2,* Benjamin Seeliger,1 Jan Fuge,1 Stephanie Korn,3 Roland Buhl,3 Maren Schuhmann,4 Felix Herth,4 Benjamin Kendziora,5 Juergen Behr,2 Nikolaus Kneidinger,2 Karl-Christian Bergmann,5 Christian Taube,6 Tobias Welte,1 Hendrik Suhling1 1Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 2Department of Internal Medicine V, Ludwig-Maximilians University of Munich (LMU), Munich, Germany; 3Pulmonary Department, Mainz University Hospital, Mainz, Germany; 4Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany; 5Allergy-Centre-Charité, Charité – Universitätsmedizin Berlin, Berlin, Germany; 6Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Essen, Germany*These authors contributed equally to this workCorrespondence: Hendrik Suhling Email suhling.hendrik@mh-hannover.deBackground: Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy.Methods: In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under anti-IL-5 therapy) and timepoint 2 (T2, under anti-IL-5Rα therapy).Results: Of 665 patients treated with anti-IL-5 antibodies, 70 were switched to anti-IL-5Rα and 60 were included in the analysis. Median treatment duration was 8 months [IQR 5; 15] for anti-IL-5 and 5 months [IQR 4; 6] for anti-IL-5Rα therapy. FEV1 was 61% of predicted at BL [IQR 41; 74], 61% [IQR 43; 79] at T1 and 68% [IQR 49; 87] at T2 (pT1-T2=0.011). ACT score was 10 [IQR 8; 13], 16 [IQR 10; 19] and 19 [IQR 14; 22], respectively (both p< 0.001). The number of patients requiring OCS was reduced from 41 (BL) to 32 (T1) and 19 (T2) (both p< 0.001). Ten patients discontinued anti-IL-5Rα therapy due to insufficient efficacy (n=7) and adverse events (n=3).Conclusion: Switching from anti-IL-5 to anti-IL-5Rα therapy in patients with inadequate response was associated with significantly improved FEV1, asthma control and OCS reduction.Keywords: benralizumab, eosinophils, mepolizumab, reslizumab, severe asthma

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

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

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