Comparison of cryobiopsy and forceps biopsy for the diagnosis of mediastinal lesions: A randomised clinical trial.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard approach for lung cancer staging. However, its diagnostic utility for other mediastinal diseases might be hampered by the limited tissue retrieved. Recent evidence suggests the novel sampling strategies of forceps biopsy and cryobiopsy as auxiliary techniques to EBUS-TBNA, considering their capacity for larger diagnostic samples. METHODS: This study determined the added value of forceps biopsy and cryobiopsy for the diagnosis of mediastinal diseases. Consecutive patients with mediastinal lesions of 1 cm or more in the short axis were enrolled. Following completion of needle aspiration, three forceps biopsies and one cryobiopsy were performed in a randomised pattern. Primary endpoints included diagnostic yield defined as the percentage of patients for whom mediastinal biopsy led to a definite diagnosis, and procedure-related complications. RESULTS: In total, 155 patients were recruited and randomly assigned. Supplementing EBUS-TBNA with either forceps biopsy or cryobiopsy increased diagnostic yield, with no significant difference between EBUS-TBNA plus forceps biopsy and EBUS-TBNA plus cryobiopsy (85.7 % versus 91.6 %, P = 0.106). Yet, samples obtained by additional cryobiopsies were more qualified for lung cancer molecular testing than those from forceps biopsies (100.0 % versus 89.5 %, P = 0.036). When compared directly, the overall diagnostic yield of cryobiopsy was superior to forceps biopsy (85.7 % versus 70.8 %, P = 0.001). Cryobiopsies produced greater samples in shorter procedural time than forceps biopsies. Two (1.3 %) cases of postprocedural pneumothorax were detected. CONCLUSIONS: Transbronchial mediastinal cryobiopsy might be a promising complementary tool to supplement traditional needle biopsy for increased diagnostic yield and tissue harvesting. TRIAL REGISTRATION: ChiCTR2000030373.

[Chronic cough]. / Chronischer Husten.

Coughing is an important protective reflex of the respiratory tract and primarily serves clearance of the bronchial system. It is also an exceptionally common symptom in outpatient care that can be an expression of a variety of diseases. Coughing duration of longer than 8 weeks is referred to as chronic cough. A structured, often interdisciplinary diagnostic process is essential. The aim here is to identify causal treatment options, avoiding overdiagnosis and simultaneously not overlooking severe illness. This article discusses current diagnostic procedures, important differential diagnoses and possible treatment options.

Position statement on endoscopic lung volume reduction in South Africa: 2022 update.

Chronic obstructive pulmonary disease (COPD) remains one of the most common causes of morbidity and mortality in South Africa. Endoscopic lung volume reduction (ELVR) was first proposed by the South African Thoracic Society (SATS) for the treatment of advanced emphysema in 2015. Since the original statement was published, there has been a growing body of evidence that a certain well-defined sub-group of patients with advanced emphysema may benefit from ELVR, to the point where the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines and the United Kingdom National Institute for Health and Care Excellence (NICE) advocate the use of endoscopic valves based on level A evidence. Patients aged 40 - 75 years with severe dyspnoea (COPD Assessment Test score ≥10) despite maximal medical therapy and pulmonary rehabilitation, with forced expiratory volume in one second (FEV1) 20 - 50%, hyperinflation with residual volume (RV) >175% or RV/total lung capacity (TLC) >55% and a six-minute walking distance (6MWD) of 100 - 450 m (post-rehabilitation) should be referred for evaluation for ELVR, provided no contraindications (e.g. severe pulmonary hypertension) are present. Further evaluation should focus on the extent of parenchymal tissue destruction on high-resolution computed tomography (HRCT) of the lungs and interlobar collateral ventilation (CV) to identify a potential target lobe. Commercially available radiology software packages and/or an endobronchial catheter system can aid in this assessment. The aim of this statement is to provide the South African medical practitioner and healthcare funders with an overview of the practical aspects and current evidence for the judicious use of the valves and other ELVR modalities which may become available in the country.

[Smoking-toxic substances and immunological consequences]. / Rauchen ­ Noxen und immunologische Folgen.

BACKGROUND: Tobacco smoke is the leading cause of morbidity and mortality in modern times. The combustion products in tobacco smoke contain a variety of toxic substances. FINDINGS: These substances have far-reaching effects on the immune system, altering both cell-mediated and humoral responses of the immune system. Hence, they affect the development, cytokine production, and effector function of both innate immune cells, including dendritic cells (DCs), macrophages, and natural killer (NK) cells, and adaptive immune cells, such as cytotoxic CD8+ T cells, CD4+ Th cells, regulatory T cells, and B cells, resulting in proinflammatory responses and/or immune cell dysfunction. CONCLUSION: However, although tobacco products have been shown to impair humoral and cell-mediated immunity, neither the extent of this impairment nor its mechanisms are clearly understood.

Association of the advanced lung cancer inflammation index (ALI) with immune checkpoint inhibitor efficacy in patients with advanced non-small-cell lung cancer.

BACKGROUND: The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. RESULTS: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. CONCLUSIONS: The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer.

BACKGROUND: The improved efficacy of tyrosine kinase inhibitors (TKI) mandates reappraisal of local therapy (LT) for brain metastases (BM) of oncogene-driven non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This study included all epidermal growth factor receptor-mutated (EGFR+, n = 108) and anaplastic lymphoma kinase-rearranged (ALK+, n = 33) TKI-naive NSCLC patients diagnosed with BM in the Thoraxklinik Heidelberg between 2009 and 2019. Eighty-seven patients (62%) received early LT, while 54 (38%) received delayed (n = 34; 24%) or no LT (n = 20; 14%). LT comprised stereotactic (SRT; n = 40; 34%) or whole-brain radiotherapy (WBRT; n = 77; 66%), while neurosurgical resection was carried out in 19 cases. RESULTS: Median overall survival (OS) was 49.1 months for ALK+ and 19.5 months for EGFR+ patients (P = 0.001), with similar median intracranial progression-free survival (icPFS) (15.7 versus 14.0 months, respectively; P = 0.80). Despite the larger and more symptomatic BM (P < 0.001) of patients undergoing early LT, these experienced longer icPFS [hazard ratio (HR) 0.52; P = 0.024], but not OS (HR 1.63; P = 0.12), regardless of the radiotherapy technique (SRT versus WBRT) and number of lesions. High-risk oncogene variants, i.e. non-del19 EGFR mutations and 'short' EML4-ALK fusions (mainly variant 3, E6:A20), were associated with earlier intracranial progression (HR 2.97; P = 0.001). The longer icPFS with early LT was also evident in separate analyses of the EGFR+ and ALK+ subsets. CONCLUSIONS: Despite preferential use for cases with poor prognostic factors, early LT prolongs the icPFS, but not OS, in TKI-treated EGFR+/ALK+ NSCLC. Considering the lack of survival benefit, and the neurocognitive effects of WBRT, patients presenting with polytopic BM may benefit from delaying radiotherapy, or from radiosurgery of multiple or selected lesions. For SRT candidates, the improved tumor control with earlier radiotherapy should be weighed against the potential toxicity and the enhanced intracranial activity of newer TKI. High-risk EGFR/ALK variants are associated with earlier intracranial failure and identify patients who could benefit from more aggressive management.

[Guideline for Long-Term Oxygen Therapy - S2k-Guideline Published by the German Respiratory Society]. / Leitlinie zur Langzeit-Sauerstofftherapie.

Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008.

Long-term Survival Results following Endobronchial RF Ablation in a Healthy-Porcine Model.

This paper presents results from long-term survival study where healthy swine were ablated with a novel technology designed for treating early-stage non-small cell lung cancer using an endobronchial flexible catheter.Methods - The radiofrequency ablation (RFA) system has been presented previously and consisted of an ablation catheter, radiofrequency generator, irrigation pump for infusion of hypertonic saline (HS) and a laptop. The catheter carried an occlusion balloon, a 5 mm long RF electrode, with irrigation holes, and a 1 mm long electrode for bipolar impedance measurements. The outer diameter (OD) was 1.4 mm for compatibility with current bronchoscopes, navigation systems and radial EBUS. Nine swine were treated in this study with survival times of 1, 4 and 12 weeks (N=3 at each time point). In all animals, the treatment sites consisted of one location in the upper right lung (RUL) and another one in the lower right lung (RLL). CTs were taken pre-op, immediately post-op and at every 2 weeks post treatment. Ablation times ranged from 6 to 8 min and average applied power was 68 W (range 63 - 72 W).Results - At 1-week survival, large zones of necrotic tissue were observed in all respective 6 ablations. Ablation volumes had an average diameter of 3.2 cm at RUL locations and 3.8 cm in RLLs (likely due to longer RLL ablation durations). As time progressed, the necrotic tissue was gradually replaced with fibrotic tissue. At 4-week survival, the replacement was almost complete in all respective 3 animals. As a result, ablation volumes decreased to an average diameter of 1.3 cm at RUL locations and 2.3 cm in RLLs (likely due to longer RLL ablation durations). At 12-week survival, as the replacement process continued, histopathology revealed zones of residual necrotic tissue that were further reduced in size. Ablation zones had been resorbed and contracted by fibrous scar tissue. The average volume of the treatment effect decreased to 1.1 cm (RUL) and to 1.6 cm (RLL) in equivalent diameter. There were no complications in any of the nine animals.Conclusion - In healthy swine lungs, RFA with a 1.4-mm OD, radial-EBUS-sheath-compatible, endobronchial catheter was effective and safe. This system and therapeutic approach may be considered for further evaluation in minimally invasive treatment of tumorous lung nodules.

Risk stratification of EGFR+ lung cancer diagnosed with panel-based next-generation sequencing.

OBJECTIVE: Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. MATERIALS AND METHODS: To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). RESULTS: EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. CONCLUSIONS: EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC.

[Treatment recommendations for mechanical ventilation of COVID­19 patients]. / Behandlungsempfehlungen zur Beatmung von COVID­19-Patienten.

Background: Due to the novelty of COVID­19 there is lack of evidence-based recommendations regarding the mechanical ventilation of these patients. Objective: Identification and delineation of critical parameters enabling individualized lung and diaphragm protective mechanical ventilation. Material and methods: Selective literature search, critical evaluation and discussion of expert recommendations. Results: In the current literature a difference between ARDS in COVID­19 and classical ARDS is described; however, there are no evidence-based recommendations for dealing with this discrepancy. In the past parameters and approaches for a personalized mechanical ventilation strategy were already introduced and applied. Conclusion: Using the parameters presented here it is possible to individualize the mechanical ventilation of COVID­19 patients in order to adjust and increase its compatibility to the heterogeneous clinical presentation of the COVID­19 ARDS.

Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET.

We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1-4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off ≤2) and all-cause mortality over 3 years of follow-up were determined by logistic and Cox regression analyses, with sex, age, BMI and pack years as covariates. Predictive values were evaluated by ROC curves. Capillary blood gases included SaO2, PaO2, PaCO2, pH, BE and the concentration of OxyHem [haemoglobin (Hb) x fractional SaO2, g/dL] as a simple-to-measure correlate of oxygen content. Inflammatory markers were WBC, CRP, IL-6 and -8, TNF-alpha and fibrinogen, and comorbidities comprised a broad panel including cardiac and metabolic disorders. Among BG, OxyHem was associated with dyspnoea, exacerbation history, BODE-Index and mortality. Among inflammatory markers and comorbidities, only WBC and heart failure were consistently related to all outcomes. ROC analyses indicated that OxyHem provided information of a magnitude comparable to that of WBC, with optimal cut-off values of 12.5 g/dL and 8000/µL, respectively. Regarding mortality, OxyHem also carried independent, additional information, showing a hazard ratio of 2.77 (95% CI: 1.85-4.15, p < 0.0001) for values <12.5 g/dL. For comparison, the hazard ratio for WBC > 8000/µL was 2.33 (95% CI: 1.60-3.39, p < 0.0001). In stable COPD, the concentration of oxygenated hemoglobin provided additional information on disease state, especially mortality risk. OxyHem can be calculated from hemoglobin concentration and oxygen saturation without the need for the measurement of PaO2. It thus appears well suited for clinical use with minimal equipment, especially for GPs.

[Joint Statement of the German Radiological Society and the German Respiratory Society on a Quality-Assured Early Detection Program for Lung Cancer with Low-dose CT]. / Positionspapier der Deutschen Röntgengesellschaft und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin zu einem qualitätsgesicherten Früherkennungsprogramm des Lungenkarzinoms mittels Niedrigdosis-CT.

Substantial new data on early detection of lung cancer with low-dose CT has become available since the last joint statement of the German Roentgenological Society and the German Respiratory Society was published in 2011. The German S3 guideline on lung cancer was revised in 2018 and now contains a weak recommendation towards early detection of lung cancer with low-dose CT in a quality-assured early detection program. These new developments required a repositioning of the involved professional societies. This present joint statement describes main features of a quality-assured program for early detection of lung cancer with low-dose CT in Germany.

[Interventional treatment of tracheopleural and bronchopleural fistulas]. / Interventionelle Versorgung tracheo-/bronchopleuraler Fisteln.

BACKGROUND: Interventional bronchoscopy is an indispensable option to manage bronchopleural and tracheopleural fistulas in patients in a poor general condition and at high risk for developing postoperative complications. METHODS: This article is based on a search in the PubMed database for relevant publications and own experiences as surgeons and pneumologists. RESULTS: Various interventional techniques can be used for the treatment of bronchopleural and tracheopleural fistulas. Currently, the insertion of stents or endobronchial valves is the most frequently used treatment. Ideally, the attending anesthesiologist will have experience with high frequency jet ventilation and the attending surgeon will have experience with rigid bronchoscopy, flexible bronchoscopy, and interventional bronchoscopy. DISCUSSION: Due to a lack of standardized treatment recommendations, individual treatment plans must be decided according to the location of the bronchopleural or tracheopleural fistula and taking existing comorbidities into account.

Early Preclinical Experience with a Novel Endobronchial Radiofrequency Ablation System for Lung Cancer Treatment.

This paper introduces a novel technology for treating early-stage non-small cell lung cancer using an endobronchial approach via a flexible radiofrequency ablation (RFA) catheter. Methods - The RFA system consisted of an ablation catheter, radiofrequency generator, irrigation pump for infusion of hypertonic saline (HS) and a laptop. The catheter carried an occlusion balloon, a 5 mm long RF electrode, with irrigation holes, and a 1 mm long electrode for bipolar impedance measurements. The outer diameter was 1.4 mm for compatibility with current bronchoscopes, navigation systems and radial EBUS. The RFA system was extensively bench tested on fresh heart, liver and lung animal tissues using power levels of 30 - 60 W, RF energy delivery durations of 3 - 15 min and HS concentrations of 5% and 23.4%. Two swine were then treated at 60 W for 15 min per bronchus. Several bronchi were involved. For both animals and for all treatment sites, 20% HS was used. Animals were survived for six weeks. Results - Bench studies showed that 60 W, 7 - 15 min ablations can produce large ablation volumes, in excess of 3 - 4 cm diameter. In the chronic animal study, no clinically adverse events occurred. There was no evidence of hemorrhage. Animals vital signs, breathing patterns and their behavior were normal throughout the six-week period. Their appetite was normal and they gained weight according to expectations. The RF ablation created discrete volumes of thermal coagulative necrosis which were subsequently encapsulated ("walled off") by zones of organized fibrosis. The dimensions of coagulative necrotic sequestra met expectations, as at six weeks they exceeded volumes corresponding to 2 cm nodules, the size of tumors normally addressed in the peripheral lung by localized therapy. Conclusion - This therapy showed promise. Appropriate energy settings combined with suitable treatment locations safely produced large ablation volumes of uniform thermal coagulative necrosis. Further studies and optimization of treatment parameters can develop it into a mainstream therapy for treating early-stage lung tumors in humans.

Identification of a highly lethal V3+ TP53+ subset in ALK+ lung adenocarcinoma.

Tyrosine kinase inhibitors (TKI) have improved prognosis in metastatic anaplastic lymphoma kinase (ALK)-driven lung adenocarcinoma, but patient outcomes vary widely. We retrospectively analyzed the clinical course of all cases with assessable baseline TP53 status and/or ALK fusion variant treated at our institutions (n = 102). TP53 mutations were present in 17/87 (20%) and the echinoderm microtubule-associated protein-like 4 (EML4)-ALK variant 3 (V3) in 41/92 (45%) patients. The number of metastatic sites at diagnosis was affected more by the presence of V3 than by TP53 mutations, and highest with both factors (mean 5.3, p < 0.001). Under treatment with ALK TKI, progression-free survival (PFS) was shorter with either TP53 mutations or V3, while double positive cases appeared to have an even higher risk (hazard ratio [HR] = 2.9, p = 0.015). The negative effect of V3 on PFS of TKI-treated patients was strong already in the first line (HR = 2.5, p = 0.037) and decreased subsequently, whereas a trend for PFS impairment under first-line TKI by TP53 mutations became stronger and statistically significant only when considering all treatment lines together. Overall survival was impaired more by TP53 mutations (HR = 4.9, p = 0.003) than by V3 (HR = 2.4, p = 0.018), while patients with TP53 mutated V3-driven tumors carried the highest risk of death (HR = 9.1, p = 0.02). Thus, TP53 mutations and V3 are independently associated with enhanced metastatic spread, shorter TKI responses and inferior overall survival in ALK+ lung adenocarcinoma. Both markers could assist selection of cases for more aggressive management and guide development of novel therapeutic strategies. In combination, they define a patient subset with very poor outcome.

Expression ratio of the TGFß-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response.

In lung cancer a deregulation of Transforming Growth Factor-ß (TGFß) signaling has been observed. Yet, the impact of TGFß in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell line SK-MES1 with TGFß results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFß stimulation orchestrates the upregulation of numerous motility- and actin cytoskeleton-related genes. Among these the non-muscle myosin 10 (MYO10) showed the highest upregulation in a LUSC patient cohort of the Cancer Genome Atlas (TCGA). Knockdown of MYO10 abrogated TGFß-induced collagen gel invasion of SK-MES1 cells. The analysis of MYO10 mRNA expression in paired tissues of 151 LUSC patients with corresponding 80-month clinical follow-up data showed that the mRNA expression ratio of MYO10 in tumor and tumor-free tissue is prognostic for overall survival of LUSC patients and predictive for the response of these patients to adjuvant chemotherapy. Thus, MYO10 represents a new clinical biomarker for this aggressive disease and due to its role in cellular motility and invasion could serve as a potential molecular target for therapeutic interventions in patients with LUSC.

[Guideline for the Diagnosis and Treatment of COPD Patients - Issued by the German Respiratory Society and the German Atemwegsliga in Cooperation with the Austrian Society of Pneumology]. / Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD).

This document is a revision of the guideline for diagnosis and treatment of COPD that replaces the version from 2007. A multitude of recent reports regarding risk factors, diagnosis, assessment, prevention and pharmacological as well as non-pharmacological treatment options made a major revision mandatory. The new guideline is based on the GOLD document taking into account specifics in Germany and Austria.

The minimal important difference for target lobe volume reduction after endoscopic valve therapy.

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.