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.

Reexpansion pulmonary edema after treatment of primary spontaneous pneumothorax.

A 24-year-old male patient, without further symptoms or comorbidities presented to the emergency room with acute dyspnea after heavy lifting two days before. On auscultation an attenuated vesicular breath was noticed on the right lung. In the initial chest radiograph a right-sided primary spontaneous pneumothorax with minor mediastinal shift was diagnosed. After insertion of a 12-French chest tube the patient's clinical condition deteriorated. The following chest radiograph and computed tomography of the thorax showed a reexpansion pulmonary edema in the right lung. The patient was admitted to the ICU and supportive treatment was initiated. Pulmonary reexpansion edema after drainage of a pneumothorax is a very rare complication with mortality rates reaching up to 20%. The exact pathophysiology remains unknown. Typical Symptoms include dyspnea, hypotension, and tachycardia. To minimize the risk of a pulmonary reexpansion edema, not more than 1200-1800 ml of air should be drained at once and the drainage should be stopped when the patient starts coughing.

A multicenter, prospective, single-arm clinical investigation of a modified staged treatment algorithm using the AeriSeal system - The STAGE trial.

INTRODUCTION: Treatment with AeriSeal is an alternate treatment option to achieve lung volume reduction in patients with severe COPD and emphysema who are not eligible for valve treatment. This study aimed to assess the safety and mode of action of a modified staged treatment algorithm with a staged treatment with lower dose of AeriSeal. METHODS: We performed a prospective, multicenter feasibility study. AeriSeal was administered during two sequential bronchoscopies: 2 subsegments of a lobe treated with two 5 mL doses, followed by two 10 mL doses in a contralateral lobe after 6 weeks. RESULTS: A total of 14 patients (36% male, mean FEV1 28.4% ± 6.7% of predicted) were enrolled. Ten patients completed both treatments, four were treated unilaterally. AeriSeal treatment resulted in significant TLVR (median 220.5 mL) at 3 months follow up. There were no significant changes from baseline at 12 months in lung function, exercise capacity and quality of life. During the 3-month post-treatment period, respiratory SAEs included 5 COPD exacerbations in 4 (28.6%) subjects, post-treatment acute inflammatory response (PAIR) in 2 (14.3%) subjects, and 1 respiratory failure event in 1 (7.1%) subject. CONCLUSION: The staged and lower dosed administration of AeriSeal does not impact the overall safety profile in terms of reducing the type and frequency of respiratory SAEs previously reported for a single-stage treatment. A larger volume of AeriSeal than used in this study may be necessary to provide meaningful clinical benefits.

Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema.

BACKGROUND: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. OBJECTIVE: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. METHOD: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score at 6 months. RESULTS: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by -10.6 [-15.9 to -5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. CONCLUSION: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

Joint Statement of the German Respiratory Society and German Society of Thoracic Surgery in Cooperation with the German Radiological Society: Structural Prerequisites of Centres for Interventional Treatment of Emphysema.

Interventional treatment of emphysema offers a wide range of surgical and endoscopic options for patients with advanced disease. Multidisciplinary collaboration of pulmonology, thoracic surgery, and imaging disciplines in patient selection, therapy, and follow-up ensures treatment quality. The present joint statement describes the required structural and quality prerequisites of treatment centres. This is a translation of the German article "Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Thoraxchirurgie in Kooperation mit der Deutschen Röntgengesellschaft: Strukturvoraussetzungen von Zentren für die interventionelle Emphysemtherapie" Pneumologie. 2020;74:17-23.

Selecting Patients for Lobar Lung Volume Reduction Therapy: What Quantitative Computed Tomography Parameters Matter?

PURPOSE: Evaluation of emphysema distribution with quantitative computed tomography (qCT) prior to endoscopic lung volume reduction (ELVR) is recommended. The aim of this study was to determine which of the commonly assessed qCT parameters prior to endoscopic lung volume reduction (ELVR) best predicts outcome of treatment. MATERIALS AND METHODS: 50 patients who underwent technically successful ELVR at our institution were retrospectively analyzed. We performed quantitative analysis of the CT scans obtained prior to ELVR and carried out Mann-Whitney U-tests and a logistic regression analysis to identify the qCT parameters that predict successful outcome of ELVR in terms of improved forced expiratory volume in 1 second (FEV1). RESULTS: In the Mann-Whitney U-test, the interlobar emphysema heterogeneity index (p = 0.008) and the pulmonary emphysema score (p = 0.022) showed a statistically significant difference between responders and non-responders. In multiple logistic regression analysis only the interlobar emphysema heterogeneity index (p = 0.008) showed a statistically significant impact on the outcome of ELVR, while targeted lobe volume, total lung volume, targeted lobe emphysema score and total lung emphysema score did not. CONCLUSION: Of all commonly assessed quantitative CT parameters, only the heterogeneity index definitely allows prediction of ELVR outcome in patients with advanced chronic obstructive pulmonary disease (COPD). KEY POINTS: · Quantitative CT is recommended prior to ELVR.. · The relevance of the obtained parameters from quantitative CT remains controversial.. · This study confirms that only the emphysema heterogeneity index has a definite impact.. CITATION FORMAT: · Theilig DC, Huebner R, Neumann K et al. Selecting Patients for Lobar Lung Volume Reduction Therapy: What Quantitative Computed Tomography Parameters Matter?. Fortschr Röntgenstr 2019; 191: 40 - 47.

Predicting Lung Volume Reduction after Endobronchial Valve Therapy Is Maximized Using a Combination of Diagnostic Tools.

BACKGROUND: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) has been proven to be effective in patients with severe emphysema. However, the selection of patients without collateral ventilation prior to treatment is critical for procedural success. Collateral ventilation can be assessed directly with the Chartis system or indirectly using computed tomography (CT) fissure analysis. OBJECTIVES: We retrospectively evaluated the diagnostic value of a combination of the quantitative CT interlobar fissure completeness score (FCS) and Chartis in predicting responders to EBV therapy. METHODS: CT data from four prospective studies were pooled and analyzed using semiautomated software to quantify the completeness of interlobar fissures. These FCSs were compared to a reference standard of achieving ≥350 ml of target lobe volume reduction after EBV treatment. Using a receiver operating characteristic curve, optimal thresholds predictive of complete fissures (responders) and incomplete fissures (non-responders) were determined. A subgroup of patients with partially complete fissures was identified, where software had lower accuracy. The complementary value of Chartis was investigated in this group. RESULTS: A fissure was defined as complete (FCS >95%), incomplete (FCS <80%), or partially complete (80% < FCS < 95%). The positive predictive value (PPV) of complete fissures is 88.1%, and the negative predictive value (NPV) is 92.9%, with an overall accuracy of 89.2%. Chartis was utilized in patients with partially complete fissures, with a PPV of 82.3%, an NPV of 84.6%, and an accuracy of 83.3%. CONCLUSION: Combining diagnostic tools could reduce the burden on patients and the healthcare system while providing clinicians with a better means for patient selection for EBV therapy.

Outcomes of Endobronchial Valve Treatment Based on the Precise Criteria of an Endobronchial Catheter for Detection of Collateral Ventilation under Spontaneous Breathing.

BACKGROUND: Endoscopic lung volume reduction with valves is a valid therapeutic option for COPD patients with severe emphysema. The exclusion of interlobar collateral ventilation (CV) is an important predictor of clinical success. OBJECTIVES: Recently, a catheter-based endobronchial in vivo measurement system (Chartis, Pulmonx, USA) has become routine in the clinical evaluation of CV status in target lobes, but the criteria for phenotyping CV by Chartis evaluation have not yet been defined. We asked the questions, how many phenotypes can be identified using Chartis, what are the exact criteria to distinguish them, and how do the Chartis phenotypes respond to valve insertion? METHODS: In a retrospective study, 406 Chartis assessments of 166 patients with severe COPD were analyzed. Four Chartis phenotypes, CV positive (CV+), CV negative (CV-), low flow (LF) and low plateau were identified. Fifty-two patients without CV were treated with valves and followed for 3 months. RESULTS: The Chartis phenotypes were discriminated with respect to decline in expiratory peak flow, increase in resistance index and change in total exhaled volume after 1, 2, 3, 4 and 5 min of measurement time (p < 0.0001, ANOVA), and the cutoff criteria were defined accordingly. To examine the application of these phenotyping criteria, students applied them to 100 Chartis assessments, and they demonstrated almost perfect inter- and intraobserver agreements (x03BA; > 0.9). Compared to baseline, CV- and LF patients with ipsilateral CV- lobe showed an improvement in FEV1 (p < 0.05), vital capacity (p < 0.05) and target lobe volume reduction (p < 0.005) after valve insertion. CONCLUSION: This study describes the most prevalent Chartis phenotypes.

Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

PURPOSE: To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. MATERIALS AND METHODS: Twenty-one patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC = (aCpLo/aCpLu) × 100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. RESULTS: Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (ρ = 0.986) or ventilation (ρ = 0.979, p = 0.809) SPECT/CT images. CONCLUSION: AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.