Search

Airway obstruction; Cryobiopsy; Paediatric bronchoscopy Obstrucción de las vías respiratorias; Criobiopsia; Broncoscopia pediátrica Obstrucció de les vies respiratòries; Criobiòpsia; Broncoscòpia pediàtrica Background and objective Cryotherapy in interventional bronchoscopy is a new treatment modality, which has recently been made available for the paediatric airway. Lack of experience and safety concerns have led to hesitant adaptation. The aim of this study was to assess indications, success rates and complications of airway cryotherapy in children. Methods Bronchoscopists from medical centre performing cryotherapy in patients between 0 and 18 years were invited to participate in a prospective study based on an online questionnaire. Patient and participant data were collected between June 2020 and June 2021. Results A total of 69 cryotherapy procedures were performed in 57 patients a for three main indications: Biopsy (30), restoration of airway patency (23) and foreign body aspiration (16). The overall success rate was 93%, the remaining 7% were performed for foreign body removal and required a switch of technique. Restoration of airway patency was successfully applied in various pathologies, including mucus plugs, bronchial casts and post traumatic stenosis. The diagnostic yield of transbronchial biopsies was 96%. No severe complications were encountered; one pneumothorax following a cryobiopsy required a chest drain for 48 h. No child was admitted to intensive care or died from a procedural complication. Conclusion In this largest paediatric case collection to date, cryotherapy was safe and carried a high success rate. Cryobiopsy compares favourably to the widely used forceps biopsy and could replace it in the future. Paediatric bronchoscopists are encouraged to add cryotherapy to their armamentarium of airway interventions. Open Access funding enabled and organized by Projekt DEAL.

Purpose EGFR tyrosine kinase inhibitor (TKI) therapy in EGFR-mutated lung cancer is limited by acquired resistance. In half of the patients treated with first/second-generation (1st/2nd gen) TKI, resistance is associated with EGFR p.T790M mutation. Sequential treatment with osimertinib is highly active in such patients. Currently, there is no approved targeted second-line option for patients receiving first-line osimertinib, which thus may not be the best choice for all patients. The present study aimed to evaluate the feasibility and efficacy of a sequential TKI treatment with 1st/2nd gen TKI, followed by osimertinib in a real-world setting. Methods Patients with EGFR-mutated lung cancer treated at two major comprehensive cancer centers were retrospectively analyzed by the Kaplan–Meier method and log rank test. Results A cohort of 150 patients, of which 133 received first-line treatment with a first/second gen EGFR TKI, and 17 received first-line osimertinib, was included. Median age was 63.9 years, 55% had ECOG performance score of ≥ 1. First-line osimertinib was associated with prolonged progression-free survival (P = 0.038). Since the approval of osimertinib (February 2016), 91 patients were under treatment with a 1st/2nd gen TKI. Median overall survival (OS) of this cohort was 39.3 months. At data cutoff, 87% had progressed. Of those, 92% underwent new biomarker analyses, revealing EGFR p.T790M in 51%. Overall, 91% of progressing patients received second-line therapy, which was osimertinib in 46%. Median OS with sequenced osimertinib was 50 months. Median OS of patients with p.T790M-negative progression was 23.4 months. Conclusion Real-world survival outcomes of patients with EGFR-mutated lung cancer may be superior with a sequenced TKI strategy. Predictors of p.T790M-associated resistance are needed to personalize first-line treatment decisions.

OA Förderung 2023

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.

Objectives MET c-Cbl binding site mutations constitute about 2 % of MET exon 14 alterations in lung cancer. Preclinical data suggests regarding these mutations as functional analogs of MET exon 14 skipping mutations, but clinical validation is lacking. Results We report the case of a patient with metastastic lung adenocarcinoma harboring a c-Cbl binding site alteration and demonstrate clinical, radiological and metabolic response to crizotinib with a PFS of 10.6 months. As escape mechanism, a typical MET resistance mutation could be identified. Conclusion MET c-Cbl binding site mutations should be regarded as a distinct subtype of MET exon 14 alterations. Patients with lung cancer harboring such mutations should be offered targeted therapy.

Rebiopsies of non-small cell lung cancers (NSCLC) are mainly performed to (i) cover the evolution of potentially amenable resistance mechanisms against a targeted therapy, and (ii) to identify new therapeutic targets which were not detected in the initial diagnostic biopsy. Comprehensive systematic analyses evaluating the value of rebiopsies are missing.Clinical databases from two large comprehensive cancer center networks were queried following prespecified criteria to identify prospectively entered NSCLC cases with at least one rebiopsy at disease progression. Clinicopathological and biomarker findings including multigene sequencing were correlated with clinical outcomes.From a total of 17,477 stage IV NSCLC patients, a cohort of 403 evaluable patients undergoing at least one rebiopsy of a primary tumor or metastasis was retrieved. Changes in biomarker profiles as compared to baseline were observed in 48.9%. In 31.3% of cases, findings of potential therapeutic relevance were revealed, including 18 patients (4.4%) with a targetable marker only detected at rebiopsy. New findings were more frequent (greater than50%) in NSCLC with EGFR/ALK/ROS1 alterations, including mutations of the dominant oncogene, TP53 mutations, and MET or ERBB2 amplifications. Patients undergoing rebiopsy exhibited superior overall survival compared to a control group, irrespective of presence (HR 0.28) or absence (HR 0.20, both p 0.001) of a therapeutically targetable aberration.Rebiopsies at progression of advanced NSCLC are strongly supported by a high rate of clinically relevant findings. Current clinical practice selects a patient population with exceptional outcomes, which merits further characterization.

in press

The pivotal PACIFIC trial defined durvalumab consolidation as the new standard of care in patients with stage III non-small-cell lung cancer treated with definitive radiochemotherapy. The authors characterized the durvalumab effect after induction chemotherapy according to the ESPATUE trial and definitive radiochemotherapy. All consecutive patients with stage III non-small-cell lung cancer receiving definitive radiochemotherapy between January 2017 and February 2020 were included. Primary end points were progression-free survival and overall survival. Altogether, 160 patients (75 PD-L1-positive, 62 PD-L1-negative, 23 unknown) received definitive radiochemotherapy, 146 (91%) of whom received prior induction chemotherapy. Durvalumab consolidation showed high effectiveness overall and in the good-risk group according to the PACIFIC trial (log-rank test: p < 0.005). Hazard ratios for progression-free survival and overall survival were at the lower limits of those in the PACIFIC trial. These results were robust to adjustment for potential confounders by propensity score weighting. Eastern Cooperative Oncology Group (ECOG) performance status was the most important pretreatment prognostic factor. Tweetable abstract High effectiveness according to the PACIFIC and ESPATUE trials: patients were treated with induction chemotherapy, definitive radiochemotherapy and consolidation immunotherapy. A durable and remarkable tumor response was achieved in the real-world clinical routine. Plain language summary The PACIFIC trial is the major landmark trial for stage III non-small-cell lung cancer (NSCLC) patients treated with combined chemoradiation and defined immunotherapy as maintenance treatment and the new standard of care in patients with stage III NSCLC. Here the authors report a retrospective study comparing consecutive stage III NSCLC patients receiving induction chemotherapy and definitive chemoradiation with or without durvalumab consolidation in a high-volume lung cancer center. After induction chemotherapy, chemoradiation and immune checkpoint inhibition, a durable and remarkable tumor response can be achieved in the clinical routine. Consolidation immunotherapy with durvalumab can be confirmed as a strong innovative therapeutic option in NSCLC in almost all subgroups of patients.

Abstarct Background To examine long-term-survival of cT4 cN0/1 cM0 non-small-cell lung carcinoma (NSCLC) patients undergoing definitive radiochemotherapy (ccRTx/CTx) in comparison to the trimodality treatment, neoadjuvant radiochemotherapy followed by surgery, at a high volume lung cancer center. Methods All consecutive patients with histopathologically confirmed NSCLC (cT4 cN0/1 cM0) with a curative-intent-to-treat ccRTx/CTx were included between 01.01.2001 and 01.07.2019. Mediastinal involvement was excluded by systematic EBUS-TBNA or mediastinoscopy. Following updated T4-stage-defining-criteria initial staging was reassessed by an expert-radiologist according to UICC-guidelines [8th edition]. Outcomes were compared with previously reported results from patients of the same institution with identical inclusion criteria, who had been treated with neoadjuvant radiochemotherapy and resection. Factors for treatment selection were documented. Endpoints were overall-survival (OS), progression-free-survival (PFS), and cumulative incidences of isolated loco-regional failures, distant metastases, secondary tumors as well as non-cancer deaths within the first year. Results Altogether 46 consecutive patients with histopathologically confirmed NSCLC cT4 cN0/1 cM0 [cN0 in 34 and cN1 in 12 cases] underwent ccRTx/CTx after induction chemotherapy (iCTx). Median follow-up was 133 months. OS-rates at 3-, 5-, and 7-years were 74.9%, 57.4%, and 57.4%, respectively. Absolute OS-rate of ccRTx/CTx at 5 years were within 10% of the trimodality treatment reference group (Log-Rank p = 0.184). The cumulative incidence of loco-regional relapse was higher after iCTx + ccRT/CTx (15.2% vs. 0% at 3 years, p = 0.0012, Gray’s test) while non-cancer deaths in the first year were lower than in the trimodality reference group (0% vs 9.1%, p = 0.0360, Gray’s test). None of the multiple recorded prognostic parameters were significantly associated with survival after iCTx + ccRT/CTx: Propensity score weighting for adjustment of prognostic factors between iCTx + ccRT/CTx and trimodality treatment did not change the results of the comparisons. Conclusions Patients with cT4 N0/1 M0 NSCLC have comparable OS with ccRTx/CTx and trimodality treatment. Loco-regional relapses were higher and non-cancer related deaths lower with ccRTx/CTx. Definitive radiochemotherapy is an adequate alternative for patients with an increased risk of surgery-related morbidity.

Johannes Wienker, Kaid Darwiche, Julia Wälscher, Jane Winantea, Michael Hagemann, Erik Büscher, Abhinav Singla, Christian Taube, Rüdiger Karpf-Wissel Department of Pneumology, University Medicine Essen- Ruhrlandklinik, Essen, Nordrhein-Westfalen, GermanyCorrespondence: Johannes Wienker, Department of Pneumology, University Medicine Essen- Ruhrlandklinik, Tüschener Weg 40, Essen, Nordrhein-Westfalen, 45239, Germany, Tel +49 2014334222, Fax +49 2014331988, Email johannes.wienker@stud.uni-due.deBackground: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) can be a successful treatment for end-stage emphysema patients. The reduction of hyperinflation enhances ventilatory mechanics and diaphragm function. Understanding predictors for treatment success is crucial for further improvements.Purpose: The aim of this study was to assess the effect of the target lobe volume reduction (TLVR) in relation to the ipsilateral lung volume reduction (ILVR), affected by the compensatory expansion of the adjacent lobe, on the outcome after BLVR with valves.Patients and Methods: The volumetric relationship of ILVR% to TLVR%, addressed as Reduction Ratio (R), was recorded in 82 patients and compared to changes in lung function, physical performance and quality of life. A small value for R implies a relatively low volume reduction of the ipsilateral lung (ILVR) compared to the volume reduction of the target lobe (TLVR). Additionally, the minimal clinically important difference (MCID) for R was calculated.Results: Patients with a smaller Reduction Ratio (R < 0.2) showed minor improvements at the 3 months follow-up compared to patients with R ≥ 0.2 (mean changes of 39 mL (5.8%), – 395 mL (– 4.9%) and 96 mL (7.1%) versus 231 mL (33%), – 1235 mL (– 20%) and 425 mL (29%) in the forced expiratory volume in 1s (FEV1), residual volume (RV) and inspiratory vital capacity (IVC), respectively, and – 3 m and 0 points versus 20.4 m and – 3.4 points in the 6-minute-walking-distance (6MWD) and COPD assessment test (CAT) score respectively). With a combined value of 0.185, a MCID for R was calculated with established anchors (FEV1, RV, and 6MWD) for emphysema patients.Conclusion: Extensive compensatory hyperinflation of the adjacent non-treated lobe after BLVR results in decreased ILVR, which is responsible for a lack of meaningful improvements in ventilatory mechanics and clinical outcome, despite technically successful lobe volume reduction.Keywords: emphysema, ipsilateral lung volume, reduction ratio, volume shift

CA extern

Accurate determination of lymph-node (LN) metastases is a prerequisite for high precision radiotherapy. The primary aim is to characterise the performance of PET/CT-based machine-learning classifiers to predict LN-involvement by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in stage-III NSCLC. Prediction models for LN-positivity based on [18F]FDG-PET/CT features were built using logistic regression and machine-learning models random forest (RF) and multilayer perceptron neural network (MLP) for stage-III NSCLC before radiochemotherapy. A total of 675 LN-stations were sampled in 180 patients. The logistic and RF models identified SUVmax, the short-axis LN-diameter and the echelon of the considered LN among the most important parameters for EBUS-positivity. Adjusting the sensitivity of machine-learning classifiers to that of the expert-rater of 94.5%, MLP (P = 0.0061) and RF models (P = 0.038) showed lower misclassification rates (MCR) than the standard-report, weighting false positives and false negatives equally. Increasing the sensitivity of classifiers from 94.5 to 99.3% resulted in increase of MCR from 13.3/14.5 to 29.8/34.2% for MLP/RF, respectively. PET/CT-based machine-learning classifiers can achieve a high sensitivity (94.5%) to detect EBUS-positive LNs at a low misclassification rate. As the specificity decreases rapidly above that level, a combined test of a PET/CT-based MLP/RF classifier and EBUS-TBNA is recommended for radiation target volume definition.

Simple Summary Neoadjuvant immunotherapy is a novel approach for lung cancer patients in stages where curative intent treatment is possible. The rationale is a based on the idea that recognition by the immune system is activated by the entire tumor prior to surgical resection. Promising pathologic response rates have been reported and the impact on survival is currently investigated in ongoing studies. Abstract In early-stage lung cancer, recurrences are observed even after curative resection. Neoadjuvant immunotherapy might be a promising approach to eliminate micrometastasis and to potentially reduce recurrence rates and improve survival. Early trials have shown encouraging rates of pathologic response to neoadjuvant therapy and have demonstrated that surgery can be safely performed after neoadjuvant immunotherapy with various agents and in combination with chemo-(radio)therapy. However, whether these response rates translate into improved disease-free survival rates and overall survival rates remains to be determined by ongoing phase III studies.

Background Tracheal and laryngotracheal surgery provides both excellent functional results and long-term outcomes in the treatment of tracheal stenosis. Consequently, challenging re-resections are rarely necessary. The purpose of this study was to compare the outcome of (laryngo-)tracheal re-resection and surgery after bronchoscopic interventions with that of primary surgery. Methods Patients undergoing resection for benign tracheal stenosis at our center between 1/2016 and 4/2020 were included. Perioperative characteristics and functional outcomes of patients were used for statistical analysis. Results Sixty-six patients who underwent (laryngo-)tracheal resection were included (previous resection [A = 6], previous stent [B = 6], previous bronchoscopic intervention w/o stenting [C = 19], untreated [D = 35]). Baseline parameters were largely comparable between groups with exception from group B that had significantly worse lung function. Group A necessitated more complex reconstructions (end-to-end: n = 1: 17%| cricotracheal n = 2: 33%| cricotracheal with mucosectomy n = 2: 33%| laryngoplasty: n = 1: 17%) than patients in group D (end-to-end n = 21: 60%| cricotracheal n = 14: 40%). Postoperative outcomes were comparable throughout groups (intensive care unit: 1[1–18] days; hospital stay: 8[5–71] days). Anastomotic complications were higher after previous stenting (A: 0%; B: 33.3%; C: 10.5%; D: 2.9%; B/D p = 0.008| surgical revisions: A: 16.7%; B: 33.3%; C: 0%; D: 5.7%; B/D, p = 0.035). Overall, postoperative lung function was significantly better (forced expiratory volume in 1 second: 63% ± 24 vs. 75% ± 20; p = 0.001 | PeakEF 3.3 ± 1.9 vs. 5.0 ± 2.2L; p = 0.001). No 90-day mortality was observed in any group. Median follow-up was 12(1–47) months. Conclusion In carefully selected patients treated in a specialized center, tracheal or laryngotracheal resection after previous tracheal interventions provides comparable outcome to primary surgery.

Durch die steigende Anzahl an durchgefuhrten Thorax-Computertomographie(CT)-Untersuchungen in den letzten Jahren nimmt die Rate an zufallig entdeckten peripheren Lungenherden zu. Die fruhe Diagnosestellung geht bei Lungenkarzinomen einher mit einer Verbesserung der Prognose dieser meist todlich verlaufenden Erkrankung. Die diagnostische Sicherheit der Bronchoskopie mit konventionellen bioptischen Moglichkeiten (transbronchiale Zangenbiopsie unter Rontgendurchleuchtung) ist niedrig. Ein operatives Vorgehen sollte angestrebt werden, wenn kein begrundeter Zweifel an der Malignitat besteht und keine relevanten Komorbiditaten vorliegen. Bildgebende Verfahren, wie die 18F-Fluordeoxyglukose-Positronenemissionstomographie/Computertomographie (FDG-PET/CT) konnen die Dignitat eines Herds nicht sicher klaren und sind in dieser Situation wenig hilfreich. Die Verbesserung der diagnostischen Sicherheit durch eine histologische Sicherung, meist durch bronchoskopische Probeentnahme, sollte in dieser Situation gepruft werden. In den letzten Jahren wurden mehrere bronchoskopische Verfahren entwickelt, welche die diagnostische Sicherheit von peripheren Lungenherden deutlich erhohen. Durch die verbesserte Erreichbarkeit der Herde kommt zukunftig die Moglichkeit einer bronchoskopischen Lokaltherapie in Betracht.

Endobronchial ultrasound-guided transbronchial needle aspirations (EBUS-TBNAs) are well established for staging lung cancer. A growing number of publications report on lymphoma diagnosis via EBUS-TBNA-acquired cytology; however current guidelines recommend histologic diagnosis. Research on the value of EBUS-TBNA-acquired cytology versus surgical-acquired histology in the diagnosis of lymphoma is lacking.We conducted a retrospective review of patients with mediastinal lymphoma diagnosed between 2010 and 2016. Mediastinal lymphadenopathy was accessible through both EBUS-TBNAs and surgical procedures. All data were extracted from our clinic's medical database and analyzed.Fifty-one patients newly diagnosed with lymphoma in the mediastinum were identified (median age, 43.5 years; mean age, 48.6 ± 20.6 years). A minimally invasive procedure was performed as a first diagnostic step in 29 patients, whereas surgical biopsy was performed in the remaining 22. The time to final diagnosis was significantly longer if a minimally invasive procedure was performed first compared with a surgical procedure (mean, 44 days [median, 38 days] vs 16 days [median, 8 days]; p0.030). The number of procedures to obtain a final diagnosis ranged from one to five (median, 2 procedures per patient) in the EBUS-TBNA group. This was significantly higher than that in the surgical group (median, 1 procedure per patient; p0.00005).We demonstrate that surgical biopsies are safe and well tolerated for lymphoproliferative disease diagnosis and lead to a final diagnosis in the shortest possible time. Unnecessary procedures were significantly reduced if a surgical biopsy was performed as the first step.

BACKGROUND: Bronchoscopic cryobiopsy is a new method of bronchoscopic tissue sampling in interstitial lung disease. In case of transbronchial biopsies, the resultant tissue samples are of high quality, and the lung parenchyma seen in the samples is adequate for a histological diagnosis in most cases. Bleeding after transbronchial biopsy is the most important procedure- associated complication and may be life threatening. This study addresses the risk of bleeding of transbronchial cryobiopsy. METHODS: In this prospective, randomized, controlled multicentre study 359 patients with interstitial lung disease requiring diagnostic bronchoscopic tissue sampling were included. Both conventional transbronchial forceps biopsy and transbronchial cryobiopsy were undertaken in each patient. The sequence of the procedures was randomized. Bleeding severity was evaluated semi-quantitatively as "no bleeding", "mild" (suction alone), "moderate" (additional intervention) or "severe" (prolonged monitoring necessary or fatal outcome), for each intervention. RESULTS: In 359 patients atotal of 1160 cryobiopsies and 1302 forceps biopsies were performed. Bleeding was observed after forceps biopsy in 173 patients (48.2%) and after cryobiopsy in 261 patients (72.7%). Bleeding was significantly greater in the cryobiopsy group (cryobiopsy/forceps biopsy: no bleeding 27.3%/51.8%; mild 56.5%/44.0%; moderate 15.0%/4.2%; severe 1.2%/0%; p

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. 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). 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

Major advances in molecular profiling for available targeted treatments and immunotherapy for lung cancer have significantly increased the complexity of tissue-based diagnostics. Endobronchial ultrasound-guided transbronchial needle aspirations (EBUS-TBNA) are commonly performed for diagnostic biopsies and lymph node staging. EBUS-TBNA has increasingly become one of the main sources of tumor cells for molecular analyses. As a result, there is a growing need for high quality EBUS-TBNA samples with adequate cellularity. This has increased the technical demands of the procedure and has created additional challenges, many of which are not addressed in the current EBUS guidelines. This review provides an overview of current evidence on the technical aspects of EBUS-TBNA in light of comprehensive sample processing for personalized lung cancer management. These include sonographic lymph node characterization, optimal needle choice, suction biopsy technique, and the role of rapid on-site evaluation. Attention to these technical details will be important to maximize the throughput of EBUS-TBNA biopsies for molecular testing.

Objective BRAF mutations have been subtyped in three functional classes with different oncogenic modes of action. The clinical impact of BRAF mutational subtypes in non–small-cell lung cancer (NSCLC) remains to be defined. So far, ambiguous results were reported from analyses of heterogeneous patient cohorts. Methods We studied patients with metastatic or recurrent NSCLC who were sequentially enrolled in precision oncology programs at two large German lung cancer centres from 2009 to 2019. The study period allowed evaluating the specific impact of BRAF V600E-targeting. Results In a cohort of 72 patients, BRAF mutation subtyping revealed p.V600E mutations in 31 cases (43%), whereas 41 cases (57%) harboured 18 different BRAF mutational subtypes of functional classes II/III. Functionally relevant comutations were observed in 6.4% of class I, and 24.4% of class II/III BRAF mutations. Most patients were treated with chemotherapy. Targeted therapy was administered in 11 patients with a response rate of 72.7%. PD-1/PD-L1-immunotherapy was given in 14 patients with a response rate of 28.6%. Overall survival of patients with BRAF-mutated NSCLC was inferior (HR 1.38, p = 0.048) as compared to patients with BRAF wild-type cancers. Median time-to-treatment-failure with BRAF-targeting agents was shorter as compared to approved targeted therapy of other oncogenic drivers (HR 1.97, p = 0.05). Survival outcomes were not impacted by BRAF mutation subtype functional class. Conclusions Patients with BRAF-mutated NSCLC have an inferior prognosis, which is not determined by BRAF mutation functional class. In contrast to NSCLC with other tractable driver mutations, BRAF-mutated NSCLC exhibit high susceptibility to immune checkpoint inhibitors.

Background/introduction In contrast to patients who present with advanced stage lung cancer and associated poor prognosis, patients with early-stage lung cancer may be candidates for curative treatments. The results of the NELSON lung cancer screening trial are expected to stimulate the development and implementation of a lung cancer screening strategy in most countries. Widespread use of chest computed tomography scans will also result in the detection of solitary pulmonary nodules. Because reliable biomarkers to distinguish between malignant and benign lesions are lacking, tissue-based histopathological diagnostics remain the gold standard. In this study, we aimed to establish a test to assess the predictive ability of DNA hypermethylation of SHOX2 and PTGER4 in plasma to discriminate between patients with 1.) lung cancer, 2.) benign lesions, and 3.) patients with chronic obstructive pulmonary disease (COPD). Patients and methods We retrospectively analysed SHOX2 and PTGER4 methylation in 121 prospectively collected plasma samples of patients with lung cancer (group 1A), benign lesions (group 1B), and COPD without nodules (group 2). Results PTGER4 DNA hypermethylation was more frequently observed in patients with lung cancer than in controls (p = 0.0004). Results remained significant after correction for tumour volume, smoking status, age, and eligibility for the NELSON trial. Conclusions Detection of methylated PTGER4 in plasma DNA may serve as a biomarker to support clinical decision-making in patients with pulmonary lesions at lung cancer screening in high-risk populations. Further exploration in prospective studies is warranted.

Rationale: The long-term safety and effectiveness of bronchoscopic lung volume reduction with Zephyr endobronchial valves in subjects with severe homogeneous emphysema with little to no collateral ventilation beyond 3 months have yet to be established. Methods: Ninety-three subjects were randomized to either bronchoscopic lung volume reduction with Zephyr valves or standard of care (SoC) (1:1). Zephyr valve subjects were assessed at 3, 6, and 12 months. SoC subjects were assessed at 3 and 6 months; they were then offered crossover to Zephyr valve treatment. Results: The mean group difference (Zephyr valve – SoC) for change in FEV1 from baseline to 6 months was 16.3 ± 22.1% (mean ± SD; p < 0.001). Secondary outcomes showed the mean between-group difference for the six-minute walk distance of +28.3 ± 55.3 m (p = 0.016); St. George’s Respiratory Questionnaire, −7.51 ± 9.56 points (p < 0.001); modified Medical Research Council, −0.42 ± 0.81 points (p = 0.019); BODE index, −0.85 ± 1.39 points (p = 0.006); and residual volume of −430 ± 830 mL (p = 0.011) in favor of the Zephyr valve group. At 6 months, there were significantly more responders based on the minimal clinically important difference for these same measures in the Zephyr valve versus the SoC group. The clinical benefits were persistent at 12 months. The percentage of subjects with respiratory serious adverse events was higher in the Zephyr valve group compared to SoC during the first 30 days post-procedure but not statistically different for the Zephyr valve and SoC groups from 31 days to 6 months, and stable in the Zephyr valve group out to 12 months. There were 2 deaths in the SoC group in the 31-day to 6-month period and none in the Zephyr valve group out to 12 months. Conclusions: Bronchoscopic lung volume reduction with Zephyr valves in subjects with severe homogeneous emphysema and little to no collateral ventilation provides clinically meaningful change from baseline in lung function, quality of life, exercise capacity, dyspnea, and the BODE index at 6 months, with benefits maintained out to 12 months.

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.

Introduction: In the era of targeted therapy of lung cancer, availability of adequate specimen samples for molecular analysis is increasingly important. EBUS-TBNA is often used for tissue acquisition, and the choice of the needle might influence the rate of successful molecular analysis. This prospective study evaluated quality and quantity of specimens obtained using different EBUS-TBNA needles. Methods: Consecutive patients with advanced lung cancer referred for EBUS-TBNA were included. A 22G steel needle (N1), a more flexible needle with a nitinol stylus (N2), or a core biopsy needle (N3) were used for EBUS-TBNA. Specimens were placed on a slide and weighed before transfer of tissue into formalin and sending for histopathological analysis, immunohistochemistry and next-generation sequencing (NGS). Tumour cellularity was assessed by an experienced pathologist. Results: 50 patients (28 male;mean 62.9y) with NSCLC (adeno n=38; squamous cell n=5; large cell n=3; other n=4) were included in the analysis. 25, 12 and 13 specimens were obtained with N1,N2 and N3, respectively. Mean specimen weight was 42.6±38.0 mg. Tumour cellularity was 1000 tumour cells in 6, 5, 6, 3, 8, 9 and 12 cases, respectively. Immunohistochemistry could be performed in all but 3 cases (2 with N2, 1 with N3). NGS could be done in 41 cases (82.0%; failure in 2 cases with N1, 6 with N2, 1 with N3). Tumour cellularity, sample weight and rate of successful NGS were significantly lower when EBUS-TBNA was performed with N2. Conclusion: The needle used for EBUS-TBNA had an impact on quantity and quality of tissue obtained for molecular analysis in NSCLC.

The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival.

Background The optimal treatment for patients with locally advanced non-small-cell lung-cancer (NSCLC) cT4 cN0/1 cM0 is still under debate. The purpose of this study was to examine the long-term survival of cT4 cN0/1 cM0 NSCLC patients undergoing induction chemotherapy and concurrent radiochemotherapy before surgery. Methods All consecutive patients with confirmed NSCLC (cT4 cN0/1 cM0) treated with neoadjuvant chemotherapy, concurrent radiochemotherapy (RT/CTx) (45–46 Gy) and surgical resection between 2000 and 2015 were included. According to the UICC guidelines (8th edition), T4 stage was reanalysed by an expert radiologist. The mediastinal staging was performed by systematic EBUS-TBNA or mediastinoscopy. The primary end-point was overall-survival (OS). The power to detect an increase of early tumour-associated mortality (hazard ratio > 3.5) within the first 5 years after treatment in comparison to late deaths beyond 96 months was >80%. Results Overall, 67 patients were treated with concurrent RT/CTx. T4 criteria were fulfilled by all patients, and multiple T4 criteria by 53 patients. Seventy percent of patients had an initial PET/CT staging. The median follow-up period was 134 months. OS rates at 2, 5, 10 and 15 years were 83.6 ± 4.5%, 65.4 ± 5.9%, 53.3 ± 6.3% and 36.6 ± 6.8%, respectively. A total of 44.8% of patients achieved a pathologic complete response. In multivariable analysis, ypT category was the most predictive factor. OS at 5 years for ypT0 (n = 31) was 80.5%, and ypT1 (n = 11) was 62.5%. Main sites of failure were brain and pulmonary metastases in seven and three patients, respectively. The intercurrent annual death rate was estimated from the survival curve beyond 96 months and was found to be 4.75% (95% CI 2.40–9.27%). No significant increased mortality was observed during the first 5 years (annual death rate: 8.31% [95% CI 5.60–12.24%], hazard-ratio = 1.72 [95% CI 0.81–3.65]). Conclusions The effectiveness of this trimodality schedule is high in patients with cT4 cN0/1 cM0 NSCLC with excellent local control rates. Considering the annual death rate beyond 8 years of survival as an intercurrent death rate due to comorbidity, this treatment schedule reduces annual mortality to background even in the first 5 years after therapy.

These recommendations for physicians who perform bronchoscopy will help to protect those patients (un)-affected by the current COVID-19 pandemic, minimize the risk of transmission, and maintain clinical care for all patients.

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.

Background The worldwide impact of the coronavirus disease 2019 (COVID-19) pandemic is unprecedented. Among the aerosol generating procedures, bronchoscopy in particular is an indispensable diagnostic and therapeutic tool that comes with a high risk of infection. Therefore, national societies have issued guidance statements. However, the individual ability of bronchoscopy units to follow these recommendations is largely unknown. Methods We conducted a nationwide survey from 1 April 2020 to 7 April 2020 to which 218 German endoscopy units, 105 solely bronchoscopy and 113 interdisciplinary, responded. The survey was distributed electronically via the German Respiratory Society. Results While 17% of units did not cancel any interventions, 16% cancelled >80% of their interventions. 73% were unable to completely separate high-risk patients. Most procedural measures, such as risk stratification in patients (95%), training to handle COVID-19 patients and personal protective equipment (PPE) (91%), risk adapted use of PPE (85%) and self-monitoring for staff (84%) were adopted well. Unit managers expected shortages in PPE (74%), staff shortages (68%) and severe financial losses (63%). Conclusion In the short-term, PPE shortages are perceived to be the most imminent threat to bronchoscopic activity as a whole. In this era of uncertainty, sound evidence to guide bronchoscopy units and an international concerted effort are urgently needed to formulate recommendations on facts and adapted to local conditions as described in this study., Bronchoscopy units were partly prepared for the #COVID19 pandemic. However, sound evidence to guide units and an international concerted effort are urgently needed to formulate recommendations for future pandemics. https://bit.ly/2B8WOPe

Objective Current predictive biomarkers for PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-directed immunotherapy in non-small cell lung cancer (NSCLC) mostly focus on features of tumour cells. However, the tumour microenvironment and immune context are expected to play major roles in governing therapy response. Against this background, we set out to apply context-sensitive feature selection and machine learning approaches on expression profiles of immune-related genes in diagnostic biopsies of patients with stage IV NSCLC. Methods RNA expression levels were determined using the NanoString nCounter platform in formalin-fixed paraffin-embedded tumour biopsies obtained during the diagnostic workup of stage IV NSCLC from two thoracic oncology centres. A 770-gene panel covering immune-related genes and control genes was used. We applied supervised machine learning methods for feature selection and generation of predictive models. Results Feature selection and model creation were based on a training cohort of 55 patients with recurrent NSCLC treated with PD-1/PD-L1 antibody therapy. Resulting models identified patients with superior outcomes to immunotherapy, as validated in two subsequently recruited, separate patient cohorts (n = 67, hazard ratio = 0.46, p = 0.035). The predictive information obtained from these models was orthogonal to PD-L1 expression as per immunohistochemistry: Selecting by PD-L1 positivity at immunohistochemistry plus model prediction identified patients with highly favourable outcomes. Independence of PD-L1 positivity and model predictions were confirmed in multivariate analysis. Visualisation of the models revealed the predictive superiority of the entire 7-gene context over any single gene. Conclusion Using context-sensitive assays and bioinformatics capturing the tumour immune context allows precise prediction of response to PD-1/PD-L1-directed immunotherapy in NSCLC.

Background Deregulated signal transduction pathways play a key role in development, progression and therapeutic resistance of non-small cell lung cancers (NSCLC). The purpose of this study is to assess the downstream markers of two well-characterized pathways and to correlate them with clinical outcome. Design 670 patients with metastatic NSCLC were prospectively enrolled in a comprehensive biomarker profiling program at a single center from 2012 to 2016. Phosphorylation of extracellular signal-regulated kinase (p-ERK), and protein kinase B (p-AKT) was assessed by standardized immunohistochemistry. Product of scores for quantity and quality of staining were calculated (immunoreactive score, 0–9). Somatic mutations of Kirsten rat sarcoma viral oncogene homolog [KRAS], epithelial growth factor receptor [EGFR], v-Raf murine sarcoma viral oncogene homolog B [BRAF] and phosphatidylinositol 3-kinase [PIK3CA]) were detected by Sanger (2012-03/2015) and amplicon NGS (04/2015-02/2016). Patients enrolled during the first year (2012) were used as discovery cohort. Patients enrolled from 2013 to 02/2016 were used as validation cohort. Clinical data were retrieved from the electronic medical records and were analyzed retrospectively. Results Using a discovery cohort, we identified an immunoreactive score of p-ERK ≥3 to be prognostically relevant. The validation cohort confirmed that higher levels of p-ERK correlated with worse overall survival (OS) and higher proportion of RAS mutations. Multivariate analysis including established risk factors such EGFR, ALK or ROS mutations and metastatic disease showed a trend of a detrimental effect of high p-ERK on OS (HR 1.23, CI 0.94–1.59, p = 0.131 for p-ERK immunoreactive score ≥3) and time to treatment failure after first-line therapy in the validation cohort. Phosphorylated AKT did not correlate with clinical outcome. Conclusion While serving as a prognosticator in univariate analysis, highly phosphorylated ERK does not convey a significant prognostic effect for OS in the presence of other prognostic factors. Phosphorylated ERK indicates a higher activity of RAS in advanced NSCLC.

IntroductionThe accurate diagnosis of individual interstitial lung diseases (ILD) is often challenging, but is a critical determinant of appropriate management. If a diagnosis cannot be made after multidisciplinary team discussion (MDTD), surgical lung biopsy is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to surgical lung biopsy.MethodsThis prospective, multicentre, international study analysed the impact of TBLC on the diagnostic assessment of 128 patients with suspected idiopathic interstitial pneumonia by a central MDTD board (two clinicians, two radiologists, two pathologists). The level of confidence for the first-choice diagnoses were evaluated in four steps, as follows: 1) clinicoradiological data alone; 2) addition of bronchoalveolar lavage (BAL) findings; 3) addition of TBLC interpretation; and 4) surgical lung biopsy findings (if available). We evaluated the contribution of TBLC to the formulation of a confident first-choice MDTD diagnosis.ResultsTBLC led to a significant increase in the percentage of cases with confident diagnoses or provisional diagnoses with high confidence (likelihood ≥70%) from 60.2% to 81.2%. In 32 out of 52 patients nondiagnostic after BAL, TBLC provided a diagnosis with a likelihood ≥70%. The percentage of confident diagnoses (likelihood ≥90%) increased from 22.7% after BAL to 53.9% after TBLC. Pneumothoraces occurred in 16.4% of patients, and moderate or severe bleeding in 15.7% of patients. No deaths were observed within 30 days.InterpretationTBLC increases diagnostic confidence in the majority of ILD patients with an uncertain noninvasive diagnosis, with manageable side-effects. These data support the integration of TBLC into the diagnostic algorithm for ILD.

Background: Despite the proof of principle that gene therapy can cure various monogenic diseases, limited clinical progress has been noted for gene therapy of the respiratory system. Certain anatomic features of the lungs, along with the suboptimal gene delivery vehicles utilized up to now, have significantly delayed successful clinical practice. Thus, the need for additional improvements towards safety and efficacy of the procedure is indispensable. Objective: The objective of this work was to review the progress and limitations of gene therapy in the treatment of lung disease with a focus on monogenic disease, chronic obstructive pulmonary disease and asthma and to present studies that provide a proof of principle that it works in different model systems and in patients. Method: A thorough search was performed on the aforementioned topic using Pubmed in order to identify relevant manuscripts. Several gene therapy studies for monogenic disorders affecting other organs or systems were also taken into consideration. Results: A hundred and thirty one papers were included. Inclusion criteria regarded novel gene transfer technologies of the past decade, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for pulmonary diseases. Conclusion: Current gene transfer protocols and vector design require additional amelioration. The rapidly evolving and much promising technology of CRISPR/Cas9 might possibly overcome the hurdles posed to date for effective implementation of gene therapy and become the basis for the onset of new clinical trials.

Background Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. Patients and methods The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. Results A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33–74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995–1.015), P=0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986–1.012), P=0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. Conclusions HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Register No. Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection).

OA embargo Objectives Chromosomal rearrangements involving ROS1 define a rare entity of lung adenocarcinomas with exquisite sensitivity to molecularly targeted therapy. We report clinical outcomes and genomic findings of patients with ROS1-positive lung cancer who were prospectively identified within a multiplex biomarker profiling program at the West German Cancer Center. Methods Standardized immunohistochemical (IHC) analysis, fluorescence in situ hybridization (FISH), and hotspot mutation analyses were performed in 1345 patients with advanced cancer, including 805 patients with metastatic lung adenocarcinoma. Clinical and epidemiological data were retrieved from the institutional database. Results ROS1 positivity by IHC analysis was detected in 25 patients with lung cancer (4.8% of lung adenocarcinomas), including 13 patients (2.5%) with ROS1 FISH positivity with a cutoff of at least 15% of events. Of the ROS1 IHC analysis–positive cases, 36% presented with concomitant oncogenic driver mutations involving EGFR (six cases, five of which were clinically validated by response to EGFR-targeting agents), KRAS (two cases), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), and BRAF. Three cases initially classified as ROS1 FISH–negative passed the threshold of 15% positive events when repeat biopsies were analyzed at progression. The median overall survival of the ROS1-positive patients (104 months) was significantly superior to that of the 261 patients with EGFR/anaplastic lymphoma kinase/ROS1–negative lung adenocarcinoma (24.4 months, p = 0.044). Interestingly, the overall survival of the 13 ROS1-positive patients with lung cancer from initiation of pemetrexed-based chemotherapy was significantly prolonged when compared with that of 169 pemetrexed-treated patients with EGFR/anaplastic lymphoma kinase/ROS1–negative adenocarcinoma (p = 0.01). Conclusions ROS1-positive metastatic lung adenocarcinomas frequently harbor concomitant oncogenic driver mutations. Levels of ROS1 FISH–positive events are variable over time. This heterogeneity provides additional therapeutic options if discovered by multiplex biomarker testing and repeat biopsies. © 2016 International Association for the Study of Lung Cancer

Rationale: Targeted lung denervation (TLD) is a bronchoscopic radiofrequency ablation therapy for chronic obstructive pulmonary disease (COPD), which durably disrupts parasympathetic pulmonary nerves to decrease airway resistance and mucus hypersecretion.Objectives: To determine the safety and impact of TLD on respiratory adverse events.Methods: We conducted a multicenter, randomized, sham bronchoscopy-controlled, double-blind trial in patients with symptomatic (modified Medical Research Council dyspnea scale score, ≥2; or COPD Assessment Test score, ≥10) COPD (FEV1, 30-60% predicted). The primary endpoint was the rate of respiratory adverse events between 3 and 6.5 months after randomization (defined as COPD exacerbation, tachypnea, wheezing, worsening bronchitis, worsening dyspnea, influenza, pneumonia, other respiratory infections, respiratory failure, or airway effects requiring therapeutic intervention). Blinding was maintained through 12.5 months.Measurements and Main Results: Eighty-two patients (50% female; mean ± SD: age, 63.7 ± 6.8 yr; FEV1, 41.6 ± 7.3% predicted; modified Medical Research Council dyspnea scale score, 2.2 ± 0.7; COPD Assessment Test score, 18.4 ± 6.1) were randomized 1:1. During the predefined 3- to 6.5-month window, patients in the TLD group experienced significantly fewer respiratory adverse events than those in the sham group (32% vs. 71%, P = 0.008; odds ratio, 0.19; 95% confidence interval, 0.0750-0.4923, P = 0.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%; P = 0.52). The risk of COPD exacerbation requiring hospitalization in the 0- to 12.5-month window was significantly lower in the TLD group than in the sham group (hazard ratio, 0.35; 95% confidence interval, 0.13-0.99; P = 0.039). There was no statistical difference in the time to first moderate or severe COPD exacerbation, patient-reported symptoms, or other physiologic measures over the 12.5 months of follow-up.Conclusions: Patients with symptomatic COPD treated with TLD combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.Clinical trial registered with www.clinicaltrials.gov (NCT02058459).

Asthma bronchiale und chronische obstruktive Lungenerkrankung (COPD) sind Volkskrankheiten mit steigender Inzidenz. Welchen Beitrag konnen neue Optionen der interventionellen Pneumologie in der Therapie leisten? Darstellung der bronchialen Thermoplastie (BT) bei Asthma bronchiale und der gezielten Lungendenervierung („targeted lung denervation“, TLD) bei COPD: Prozedur, Studienlage und Patientenauswahl. Bei schwerem, unkontrolliertem Asthma konnen nach Ausschopfung aller medikamentosen Masnahmen mittels BT die Bronchialmuskulatur abladiert und eine dauerhafte Verbesserung der Krankheitskontrolle erreicht werden. Bei masiger bis schwerer COPD konnen nach Ausschopfung der Standardtherapie innerhalb klinischer Studien mit einem spezialisierten Katheter bronchoskopisch vagale Nervenfasern an den Hili abladiert werden, um eine dauerhafte Parasympathikolyse und Bronchodilatation herbeizufuhren. Neue Verfahren der interventionellen Pneumologie konnen bei obstruktiven Erkrankungen einen wichtigen Beitrag leisten. Sie befinden sich in fruhen Stadien der klinischen Entwicklung, so dass der endgultige Stellenwert noch nicht feststeht.