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ZusammenfassungDie SARS-CoV-2-Pandemie hat in erheblichem Umfang die Diagnostik und Therapie interstitieller Lungenerkrankungen (ILD) beeinflusst. Insbesondere in der Frühphase der Pandemie und unter dem Einfluss der Delta-Variante ist es zu zahlreichen COVID-19-Pneumonien gekommen, in deren Gefolge sich bestehende interstitielle Lungenerkrankungen verschlechtert haben, neue entstanden sind oder entdeckt wurden. Den Einfluss einer SARS-CoV-2-Infektion – mit oder Viruspneumonie – auf vorbestehende ILD sowie die weitere Entwicklung neu entstandener pulmonaler Infiltrate und Konsolidierungen abzuschätzen, zu diagnostizieren und angemessen zu behandeln stellt eine nahezu tägliche Herausforderung in den interdisziplinären ILD-Boards dar. Mit diesem Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungstherapie e.V. (DGP) werden auf Basis des aktuellen Wissensstandes Antworten auf die wichtigsten Fragestellungen gegeben.

ZusammenfassungDie interstitielle Lungenerkrankung bedingt durch eine rheumatoide Arthritis (RA-ILD) hat eine hohe klinische Relevanz. Sie beeinflusst nicht nur die Lebensqualität, sondern hat auch einen erheblichen Anteil an der Mortalität der rheumatoiden Arthritis. Eine RA-ILD kann sich mit allen radiologischen und histopathologischen Mustern präsentieren, die auch bei anderen interstitiellen Pneumonien auftreten. Dabei hat ein diffuser Alveolarschaden (diffuse alveolar damage, DAD), gefolgt von einer gewöhnlichen interstitiellen Pneumonie (usual interstital pneumonia, UIP) die schlechteste Prognose. Zudem hat eine akute Exazerbation der RA-ILD, welche zu jedem Zeitpunkt der Erkrankung auftreten kann, eine hohe Letalität. Ein Algorithmus zur Diagnostik und Therapie der RA-ILD ist ausstehend und wird in folgendem Beitrag thematisiert. Neben Immunsuppressiva und krankheitsmodifizierenden Medikamenten (disease-modifying antirheumatic drugs, DMARD) gewannen zuletzt Antifibrotika in der Therapie der RA-ILD an Bedeutung.

There is a general underappreciation of the spectrum of obesity-related breathing disorders and their consequences. We therefore compared characteristics of obese patients with eucapnic obstructive sleep apnea (OSA), OSA with obesity-related sleep hypoventilation (ORSH) or obesity hypoventilation syndrome (OHS) to identify the major determinants of hypoventilation.In this prospective, diagnostic study (NCT04570540), obese patients with OSA, ORSH or OHS were characterized applying polysomnography with transcutaneous capnometry, blood gas analyses, bodyplethysmography and measurement of hypercapnic ventilatory response (HCVR). Pathophysiological variables known to contribute to hypoventilation and differing significantly between the groups were specified as potential independent variables in a multivariable logistic regression to identify major determinants of hypoventilation.Twenty, 43 and 19 patients were in the OSA, ORSH and OHS group, respectively. BMI was significantly lower in OSA as compared to OHS. The extent of SRBD was significantly higher in OHS as compared to OSA or ORSH. Patients with ORSH or OHS showed a significantly decreased forced expiratory volume in 1 s and forced vital capacity compared to OSA. HCVR was significantly lower in OHS and identified as the major determinant of hypoventilation in a multivariable logistic regression (Nagelkerke RAlthough there were differences in BMI, respiratory mechanics and severity of upper airway obstruction between groups, our data support HCVR as the major determinant of obesity-associated hypoventilation.

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic disease of the lung parenchyma and terminal bronchioles caused by an allergic reaction to inhaled antigens. The immune response following antigen exposure results in lymphocytic inflammation as well as granuloma formation.The typical histologic pattern of HP consists of cellular interstitial pneumonia, cellular bronchiolitis, and epithelioid cell granulomas. The additional presence of fibrosis has a significant impact on the course as well as the prognosis of the disease and represents a therapeutic approach. Therefore, a classification into a non-fibrotic and a fibrotic phenotype is proposed.The diagnosis of HP is made by high-resolution computed tomography (HRCT) of the lung, evaluation of possible antigen exposure, and bronchoscopy with bronchoalveolar lavage and, if necessary, forceps biopsy. If the diagnosis is inconclusive, transbronchial cryobiopsy or surgical lung biopsy may need to follow. A multidisciplinary board is critical in making the diagnosis.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is of high clinical relevance. It not only affects the quality of life but also makes a significant contribution to the mortality rate of patients with rheumatoid arthritis. RA-ILD can present with all known radiological and histopathological patterns seen in other interstitial pneumonias. Among these pneumonias, diffuse alveolar damage (DAD), followed by usual interstitial pneumonia (UIP) has the worst prognosis. In addition, acute exacerbation of RA-ILD, which can occur at any time during the disease, is highly lethal. An algorithm for the diagnosis and treatment of RA-ILD is pending and will be addressed in the following article. In addition to immunosuppressants and disease-modifying antirheumatic drugs (DMARD), antifibrotics have recently gained importance in the therapy of RA-ILD.Die interstitielle Lungenerkrankung bedingt durch eine rheumatoide Arthritis (RA-ILD) hat eine hohe klinische Relevanz. Sie beeinflusst nicht nur die Lebensqualität, sondern hat auch einen erheblichen Anteil an der Mortalität der rheumatoiden Arthritis. Eine RA-ILD kann sich mit allen radiologischen und histopathologischen Mustern präsentieren, die auch bei anderen interstitiellen Pneumonien auftreten. Dabei hat ein diffuser Alveolarschaden (diffuse alveolar damage, DAD), gefolgt von einer gewöhnlichen interstitiellen Pneumonie (usual interstital pneumonia, UIP) die schlechteste Prognose. Zudem hat eine akute Exazerbation der RA-ILD, welche zu jedem Zeitpunkt der Erkrankung auftreten kann, eine hohe Letalität. Ein Algorithmus zur Diagnostik und Therapie der RA-ILD ist ausstehend und wird in folgendem Beitrag thematisiert. Neben Immunsuppressiva und krankheitsmodifizierenden Medikamenten (disease-modifying antirheumatic drugs, DMARD) gewannen zuletzt Antifibrotika in der Therapie der RA-ILD an Bedeutung.

Sleep-related breathing disorders (SRBD) may be associated with a worse prognosis in idiopathic pulmonary fibrosis (IPF). However, the prevalence of sleep disorders in IPF and the pathophysiological link between SRBD and IPF is unclear.In this prospective trial, consecutive patients with stable IPF underwent polysomnography and cardiopulmonary exercise testing. Epworth sleepiness scale, Regensburg insomnia scale, and Pittsburgh sleep quality index were evaluated. Exclusion criteria were oxygen supplementation therapy, lung emphysema, and heart failure. For pairwise comparison of categorical data, the two-proportion z-test was applied. Correlation between continuous variables was assessed via the Pearson correlation coefficient. Patients without and with SRBD were compared. To find predictors for SRBD in IPF, multivariable logistic regression was applied.A total of 74 IPF patients were evaluated and 45 patients (11 female, median age 74 years, forced vital capacity 71.3%, DLCO 53.9%) were analyzed. Any kind of sleep disorder was found in 89% of patients. SRBD was present in 49% (81% obstructive sleep apnea, 19% central sleep apnea), insomnia in 40%, and periodic leg movements in 47% of subjects. The SRBD subgroup presented with a significantly lower performance (workload(peak)%pred 86.5 vs. 101.0 (p = 0.036); V'OSRBD is frequent in IPF. Pulmonary vascular limitations may represent the pathophysiological link between IPF and SRBD. Workload(peak)%pred may be an independent risk factor for the occurrence of SRBD.

Sublobar resection is frequently performed for Non-Small Cell Lung Cancer (NSCLC) patients with ≤2 cm nodules. Frequently, both proper staging and radical lymphadenectomy are omitted in these operations. Therefore, we decided to evaluate the number of lymph node metastases and the number of postoperative nodal upstaging in patients undergoing pulmonary resection due to NSCLC with tumors ≤2 cm at our institution.Nodal upstaging, lymphangiosis- (L1), and hemangiosis carcinomatosa (V1) were analyzed. pN0 patients were compared to patients with postoperative nodal upstaging. One-, three, and five-year survival rates were measured. Survival was also assessed by the Kaplan-Meier method.747 patients underwent surgery for NSCLC at our institution between 2012 and 2020. We retrospectively reviewed data of 236 NSCLC patients with ≤2 cm tumors. The mean tumor size was 1.4 cm ± 0.39 in our cohort. Of our patients, 14% showed a cT1a tumor, and 86% of patients cT1b. 24.0 ± 12.3 lymph nodes were dissected and analyzed per patient, and 0.7 ± 2.0 of those were affected. Of our patients, 16.1% showed L1 affection, and 7.6% a V1 affection. Lymph node involvement was diagnosed in 11(4.7%) patients preoperatively. 39(16.5%) patients were upstaged due to lymph node involvement postoperatively (p 0.001). Upstaged patients showed significantly worse 3- (upstaged: 60.6% vs. pN0: 83.2%; p = 0.01) and 5-year (upstages: 38% vs. pN0 71.5%; p = 0.02) survival rates.16.5% of patients with ≤2 cm NSCLC were nodal upstaged postoperatively. These results underline that lymphadenectomy and proper staging are crucial for NSCLC patients irrespective of the tumor size and the surgical approach.

Purpose: Sublobar resection is a frequently performed surgical approach for Non-Small Cell Lung Cancer (NSCLC) patients with Methods: 747 patients underwent surgery for NSCLC at our institution between 2012 and 2020. We retrospectively reviewed data of NSCLC patients with Results: Mean tumor size was 1.4cm±0.39 in our cohort. Of our patients, 14% showed a cT1a tumor and 86% of patients cT1b. 24.0±12.3 lymph nodes were dissected and analyzed per patient, and 0.7±2.0 of those were affected. Of our patients, 16.1% showed an L1 affection and 7.6% a V1 affection. Lymph node involvement was diagnosed in 11(4.7%) patients preoperatively. 39(16.5%) patients were upstaged due to lymph node involvement postoperatively (pConclusion: Of our patients with

BackgroundIn patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD.MethodsThe ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied.ResultsIn patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required.ConclusionsTBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly “very low”.

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis. Methods: In this post hoc analysis of a prospective, randomized, controlled, multicentre study, 359 patients with ILD requiring diagnostic bronchoscopic tissue sampling were included. TBLF and TBLC were both used for each patient in a randomized order. Histological assessment was undertaken on each biopsy and determined whether sarcoid was a consideration. Results: A histological diagnosis of sarcoidosis was established in 17 of 272 cases for which histopathology was available. In 6 out of 17 patients, compatible findings were seen with both TBLC and TBLF. In 10 patients, where the diagnosis of sarcoidosis was confirmed by TBLC, TBLF did not provide a diagnosis. In one patient, TBLF but not TBLC confirmed the diagnosis of sarcoidosis. Conclusions: In this post hoc analysis, the histological diagnosis of sarcoidosis was made significantly more often by TBLC than by TBLF. As in other idiopathic interstitial pneumonias (IIPs), the use of TBLC should be considered when sarcoidosis is suspected.

Background: The number of patients receiving home long-term ventilation has risen considerably in recent decades owing to medical advancements. Experts believe that the potential for ventilator weaning or tracheostoma removal is currently insufficiently exploited. Objective: The objective of this study was to investigate the characteristics, prognosis, and decannulation/weaning potential of patients under home intensive care. Methods: In this retrospective analysis of 607 patients on home intensive care, decannulation/weaning status and survival were documented for a 2-year period after initial assessment. At the time of hospital discharge, when clinicians had deemed the weaning process concluded, an independent expert noninvasively assessed the long-term decannulation/weaning. Comparative analyses based on specific criteria, such as ventilation and decannulation/weaning status, age, and underlying diseases, were performed. Potential predictors of survival were identified via multivariable logistic regression. Results: Eighteen percent of patients were decannulated/weaned within 2 years after hospital discharge and had better mean survival than patients not decannulated/weaned (552 vs. 420 days, p < 0.001). More than half of these patients were identified to have decannulation/weaning potential based on the assessment of the independent expert. Patients with neuromuscular and neurological diseases had the best survival (546 and 501 days), patients with postsurgical conditions and cardiological diseases the worst (346 and 323 days). Underlying disease and decannulation/weaning status were significant predictors of 2-year survival. Conclusion: Successful decannulation/weaning of patients on long-term home intensive care is associated with better survival. Even in the absence of decannulation/weaning potential at the time of hospital discharge, patients may develop decannulation/weaning potential over time, which should therefore be assessed repeatedly.

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic disease of the lung parenchyma and terminal bronchioles caused by an allergic reaction to inhaled antigens. The immune response following antigen exposure results in lymphocytic inflammation as well as granuloma formation.The typical histologic pattern of HP consists of cellular interstitial pneumonia, cellular bronchiolitis, and epithelioid cell granulomas. The additional presence of fibrosis has a significant impact on the course as well as the prognosis of the disease and represents a therapeutic approach. Therefore, a classification into a non-fibrotic and a fibrotic phenotype is proposed.The diagnosis of HP is made by high-resolution computed tomography (HRCT) of the lung, evaluation of possible antigen exposure, and bronchoscopy with bronchoalveolar lavage and, if necessary, forceps biopsy. If the diagnosis is inconclusive, transbronchial cryobiopsy or surgical lung biopsy may need to follow. A multidisciplinary board is critical in making the diagnosis.

Background: Bronchoscopic thermal vapour ablation (BTVA) is an established and approved modality for minimally invasive lung volume reduction in severe emphysema. Preclinical data suggest potential for BTVA in minimally invasive ablation of lung cancer lesions. Objectives: The objective of this study is to establish the safety, feasibility, and ablative efficacy of BTVA for minimally invasive ablation of lung cancers. Methods: Single arm treat-and-resect clinical feasibility study of patients with biopsy-confirmed lung cancer. A novel BTVA for lung cancer (BTVA-C) system for minimally invasive treatment of peripheral pulmonary tumours was used to deliver 330 Cal thermal vapour energy via bronchoscopy to target lesion. Patients underwent planned lobectomy to complete oncologic care. Pre-surgical CT chest and post-resection histologic analysis were performed to evaluate ablative efficacy. Results: Six patients underwent BTVA-C, and 5 progressed to planned lobectomy. Median procedure duration was 12 min. No major procedure-related complications occurred. All 5 resected lesions were part-solid lung adenocarcinomas with median solid component size 1.32 ± 0.36 cm. Large uniform ablation zones were seen in 4 patients where thermal dose exceeded 3 Cal/mL, with complete/near-complete necrosis of target lesions seen in 2 patients. Tumour positioned within ablation zones demonstrated necrosis in >99% of cross-sectional area examined. Conclusion: BTVA of lung tumours is feasible and well tolerated, with preliminary evidence suggesting high potential for effective ablation of tumours. Thermal injury is well demarcated, and uniform tissue necrosis is observed within ablation zones receiving sufficient thermal dose per volume of lung. Treatment of smaller volumes and ensuring adequate thermal dose may be important for ablative efficacy.

Background: Cryobiopsy is an established technique that yields larger and higher-quality samples than does a forceps biopsy. However, it remains underutilised in the diagnosis of peripheral pulmonary lesions (PPLs), mainly because of difficulties in handling conventional cryoprobes. A recently introduced single-use cryoprobe with a smaller diameter and more flexibility than conventional ones may improve its diagnostic ability for PPLs. We conducted this prospective study to evaluate the feasibility of transbronchial cryobiopsy in the diagnoses of PPLs, using a new 1.7-mm cryoprobe. Methods: The study included patients with PPLs less than 30 mm in diameter scheduled to undergo bronchoscopy. All the procedures were performed using a combination of virtual bronchoscopic navigation, radial endobronchial ultrasound (R-EBUS) and X-ray fluoroscopy, and all the samples were collected using the cryoprobe alone. Thereafter, we assessed the diagnostic outcomes and safety profiles. Results: A total of 50 patients were enrolled and underwent cryobiopsy. The median lesion size was 20.8 mm (range, 8.2–29.6 mm), and the negative bronchus sign was seen in 34% of lesions. The diagnostic yield was 94% (95% confidence interval, 83.5–98.8%). A positive bronchus sign had a significantly higher diagnostic yield than did a negative bronchus sign (100% vs. 82.4%; P = 0.035). The yield was achieved regardless of other variables, including lesion size, location, and R-EBUS findings. The major complications were mild and moderate bleeding in 28% and 62% of patients, respectively. Pneumothorax was identified in one patient. Conclusion: Transbronchial cryobiopsy using the new 1.7-mm cryoprobe is a feasible procedure that has the potential to increase the diagnostic accuracy for PPLs. Trial registration Japan Registry of Clinical Trials, jRCT1032200065. Registered July 8 2020, https://jrct.niph.go.jp/en-latest-detail/jRCT1032200065

Background: Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO2) Methods: In this single-center, prospective randomized controlled trial, hospitalized patients in the respiratory department in need of diagnostic bronchoscopy were randomly assigned to a modified HFNC oxygen therapy group or a conventional oxygen therapy (COT) group. The primary outcome was the proportion of patients with a single moment of SpO2Results: Eight hundred and twelve patients were randomized to the modified HFNC (n = 406) or COT (n = 406) group. Twenty-four patients were unable to cooperate or comply with bronchoscopy. Thus, 788 patients were included in the analysis. The proportion of patients with a single moment of SpO2 p < 0.001). There were no significant differences in the fraction of inspired oxygen between the two groups. The lowest SpO2 during bronchoscopy and 5 min after bronchoscopy in the modified HFNC group was significantly higher than that in the COT group. Multivariate analysis showed that a baseline forced vital capacity (FVC) < 2.7 L (OR, 0.276; 95% CI, 0.083–0.919, p = 0.036) and a volume of fluid instilled > 60 ml (OR, 1.034; 95% CI, 1.002–1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group. Conclusion: A modified HFNC could decrease the proportion of patients with a single moment of SpO2 Trial registration ClinicalTrials. Gov: NCT02606188. Registered 17 November 2015.

The role of bronchoscopic brushing for tumor detection and molecular testing in central lung cancer is unclear. In this study, 50 consecutive subjects with suspected central lung cancer underwent bronchoscopic brushing (31 males, median age 70, 5 never smokers). Histological results were: NSCLC/SCLC/low-grade-NET/granulation tissue in 36/8/2/4 cases. Next generation sequencing (NGS) was feasible in 62% of tumor-positive brush smear samples. In 78% of these cases, NGS displayed identical results compared to histology samples, in 22% NGS from brush smears detected specific mutations, whereas DNA quality from forceps biopsy was insufficient for NGS analysis. Sensitivity, specificity, positive predictive value, negative predictive value of brush smear analysis were 66% (95% confidence interval 50-79), 100% (40-100), 100% (85-100), and 21% (7-46). For the combined analysis of brush smear, brush tip washing and sheath tube content sensitivity was slightly elevated at 69% (53-81). In central lung cancer, bronchoscopic brushing detects tumor cells in about two-third of cases and allows a decision for or against targeted therapy in the majority of tumor-positive cases on the basis of NGS analysis.

Das Coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) beherrscht weiterhin die Schlagzeilen in Deutschland, ja auf der ganzen Welt. In radikaler Weise hat die Pandemie das gesellschaftliche Leben und den medizinischen Alltag verandert. Die akribische Auswertung verfugbarer Daten aus der Versorgungsmedizin und intensive Forschungsaktivitaten ermoglichten innerhalb kurzester Zeit einen erheblichen Erkenntniszugewinn. Dieser hat unmittelbare Auswirkungen auf die tagliche Arbeit in Klinik und Praxis. Die aktuelle Ausgabe des Kompass Pneumologie versucht eine Standortbestimmung und tragt jungste medizinische Erkenntnisse zusammen, die in den letzten Monaten gewonnen wurden. Die hier getroffene Auswahl kann nur einen Bruchteil der klinischen Studien abbilden, die fur die praktische Pneumologie relevant sind. Nur ein Teil der SARS-CoV-2-Infizierten entwickelt Symptome und erkrankt an COVID-19 (Corona Virus Disease 2019). Bei Erstprasentation der Patienten ist eine Abschatzung des Risikos fur einen schweren Verlauf von hoher Bedeutung. Indikatoren, die eine wahrscheinlich erforderliche intensivmedizinische Behandlung, prognostisch relevante Komplikationen oder das Sterberisiko vorauszusagen helfen, sind hier von besonderem Interesse. Die COVID-19-Pneumonie und die Komplikation des schweren akuten Lungenversagens mit dem Bild eines ARDS stellen in der Pandemie die haufigsten und prognostisch relevantesten Herausforderungen fur den Pneumologen dar. Es kann jedoch auch zu anderen Krankheitsmanifestationen kommen, die den pneumologischen Fachbereich unmittelbar betreffen. Die Ubersichtsarbeit von Samhati Mondal et al. beleuchtet die Risikofaktoren und die Pathophysiologie thromboembolischer Erkrankungen mit Fokus auf die COVID-19-Erkrankung. Die jungst gemeinsam veroffentlichten Empfehlungen der amerikanischen und europaischen Pneumologengesellschaften (American Thoracic Society, ATS; European Respiratory Society, ERS) zur Behandlung von COVID-19 fasst Johannes Knoch in seinem Wissenstransfer zusammen. Der Artikel fuhrt eindrucklich vor Augen, wie wichtig die kritische Wurdigung der verfugbaren Evidenz bei der Erstellung von Leitlinien und Empfehlungen ist. So wird in dem Dokument zu den Therapieansatzen mit Dexamethason, Remdesivir, Hydroxychloroquin und Antikoagulanzien dezidiert Stellung genommen. Stefanie Keymel stellt in Ihrem Transfer in die Praxis die Arbeit von Ahmed M. Abdalhadi und Kollegen vor, die eine Kasuistik mit beidseitigen exsudativen lymphozytaren Pleuraergussen bei COVID-19 erlautern. Helmut Frohnhofen zeigt mit der Arbeit von Ting Guo und Mitarbeitern die klinischen Besonderheiten der COVID-19-Erkrankung bei alteren Menschen auf. So kann gerade bei den besonders alten Patienten trotz symptomarmem Erkrankungsbeginn ein komplikationstrachtiger und letztlich vital bedrohlicher Verlauf eintreten. Auch fur dieses Patientenkollektiv wurden erste klinische Risikoindikatoren identifiziert. Die COVID-19-Therapie kann beim geriatrischen Patienten nicht unreflektiert vereinheitlicht werden, sondern sollte vielmehr nach sorgfaltiger individueller Abwagung gesteuert werden. Stefan Kruger schlieslich diskutiert in seinem Wissenstransfer die Studie von Hannah Burke und Kollegen, die darin ein breites Zytokinpanel bei stationar aufgenommenen COVID-19-Patienten untersucht haben. Die Arbeit zeigt, dass Zytokin-Analysen ein weiteres Instrument zur Prognoseabschatzung darstellen konnten. Andererseits zeigt sich die Dynamik des vieldiskutierten «Zytokinsturms» heterogen und komplex, so dass sich noch kein solitarer Zytokin-Biomarker abzeichnet, der Einzug in die klinische Routine halten konnte. In der Rubrik «Erfahrung aus der Praxis» analysieren Massa Zantah und Mitarbeiter in Ihrem Patientenkollektiv retrospektiv die seltene aber klinisch hochrelevante Komplikation eines Pneumothorax bei COVID-19. Besonders bei beatmeten Patienten und radiomorphologisch auffalligen Milchglasveranderungen und Konsolidierungen sollte bei unklarer klinischer Verschlechterung ein Pneumothorax ausgeschlossen werden. Insgesamt zeigt sich auch mit dieser Auswahl an Arbeiten, dass die Pneumologie ein facettenreiches Fach ist und in besonderem Mase bei der Bewaltigung der COVID-19-Pandemie gefordert ist. Im historischen Vergleich zeichnet sich die derzeitige Pandemie dadurch aus, dass reger internationaler Erfahrungsaustausch und intensive Forschung moglich sind und diese Fruchte tragen. Ihr Dr. Lars Hagmeyer

Radical lymphadenectomy is crucial in operations for non-small cell lung cancer (NSCLC). Usually pN1 and pN2 lymph nodes are affected consecutively (N1N2). Nevertheless, pN2 metastases may also occur in the absence of pN1 as skip-N2 metastases (N0N2). Here we compare the long-term survival of N1N2- and N0N2 patients.464 patients underwent surgery for NSCLC at our institution between 2012 and 2017. We retrospectively reviewed data of pN2 stage patients (n = 68). Patients with N1N2 (n = 39) were compared to N0N2 (n = 29) patients. 1-, 3-and 5-year survival rates were measured. Survival was assessed by Kaplan-Meier curves and the cox proportional hazards model was used to identify prognostic factors for overall survival. All patients received adjuvant chemoradiation therapy according to European guidelines.The baseline characteristics did not differ between groups. We observed no differences in the histology, localization, or gender in our cohort. N0N2 patients showed significantly better 1- (N1N2: 82.4% vs. N0N2 100%; p = 0.001), 3- (14.7% vs. 63.6%; p=0.001) and 5-year (9.4% vs. 43.8%; p = 0.001) survival rates. Tumor size (Hazard ratio (HR) 1.46, Confidence interval (CI 95%) 1.03-2.04; p = 0.03) and the occurrence of N1N2 (HR 4.26, CI 2.04-8.91; p 0.0001) were independent prognostic factors for worse long-term survival. The Kaplan-Meier curves showed a reduced overall survival for N1N2 patients (log-rank N1N2, N0N2 p 0.0001).N1N2 patients have a significantly worse prognosis compared to N0N2 patients. This will aid to classify the heterogeneous pN2-NSCLC patient population more precisely. Further, multimodal therapy should be considered for N1N2 patients.

Background: The detection of PD-L1 in non-small cell lung cancer (NSCLC) is of great relevance for individualized therapy and has so far been performed using immunohistochemical analysis (IHC). With accompanying pleural effusion, the immunocytochemical analysis (ICC) could be of additive diagnostic value. Methods: 50 patients (17 women, 70±10 years, 26±5 kg/m²) with highly suspected NSCLC and pleural effusion were examined. PD-L1 expression of IHC and ICC samples were compared using the PD-L1 IHC 22C3 pharmDx Kit (Dako). Sensitivity and specificity of tumour and PD-L1 detection of ICC was determined with IHC as reference. PD-L1 was quantified according to percent of tumour cells expressing PD-L1. Due to different approval statuses of available immune checkpoint inhibitors, we considered different cut-offs for PD-L1 positivity. Results: Regarding the detection of malignancy, 7 cases with inconclusive ICC results were defined as tumour negative. Failed PD-L1 analyses were defined as PD-L1-negative. Conclusion: The detection of tumour cells in pleural punctate shows good sensitivity. PD-L1 detection is less sensitive but may still contribute to the identification of PD-L1-positive lung carcinoma. In case when invasive diagnostics (bronchoscopy, thoracoscopy) are not feasible, ICC of pleural punctate may offer a clinically valuable alternative to detect PD-L1-positive lung carcinoma with the option for 1st-line immune checkpoint inhibitor monotherapy.

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.

Objectives The number of ventilated patients is further increasing which leads to an increasing number of patients with weaning failure. In Germany, the treatment of patients with invasive out-of-hospital becomes more and more common. The aim of the study was to observe the outcome, the frequency and character of emergencies of patients with invasive out-of-hospital ventilation. Methods We conducted a prospective study over 1 year. Fifty-nine invasively ventilated patients living either at home or at nursing homes specialized in ventilator medicine were included. Results Forty-one (71%) of the patients were living in a nursing home. Chronic obstructive pulmonary disease (COPD) was the most common underlying disease (52.5%). Duration of daily ventilation did not change over the 1-year period. 52.8% of the months went without a documented emergency. The most common emergencies were oxygen desaturation (29.6%), increase of secretion (12.2%) and dyspnea (8.7%). We found no difference in the frequency of emergencies between patients cared for in their own home compared with residential care. Ten patients died during the observation period. Fewer emergencies (P = .02, CI 0.03-0.85) was the only parameter associated with a reduced mortality. Frequency of emergencies as well as survival showed no difference regarding the way patients were cared for. Conclusions In patients with invasive home mechanical ventilation survival for more than 1 year seems to be common. Only the rate of emergencies affected survival.

Epithelial-myoepithelial carcinoma is a well differentiated malignant neoplasm, which originates from the salivary glands. The primary pulmonary manifestation is rare-about 30 cases have been reported worldwide. In the literature, anatomical resection has been described as the standard surgical approach. In the presented case, a wedge resection was performed, with no evidence for tumor relapse in the follow-up reevaluation after 24 months. This is the first case report of a primary pulmonary epithelial-myoepithelial carcinoma that has been treated with a non-anatomical wedge resection and lymph node dissection as a curative approach.

Background: Therapeutic bronchoscopy (TB) is an accepted strategy for the symptomatic management of central airway malignant obstruction. Stent insertion is recommended in case of extrinsic compression, but its value in preventing airway re-obstruction after endobronchial treatment without extrinsic compression is unknown. Objective: Silicone stent Placement in symptomatic airway Obstruction due to non-small cell lung Cancer (SPOC) is the first randomized controlled trial investigating the potential benefit of silicone stent insertion after successful TB in symptomatic malignant airway obstruction without extrinsic compression. Method: We planned an inclusion of 170 patients in each group (stent or no stent) over a period of 3 years with 1-year follow-up. The 1-year survival rate without symptomatic local recurrence was the main endpoint. Recurrence rate, survival, quality of life, and stent tolerance were secondary endpoints. During 1-year follow-up, clinical events were monitored by flexible bronchoscopies and were evaluated by an independent expert committee. Results: Seventy-eight patients (mean age 65 years) were randomized into 2 arms: stents (n = 40) or no stents (n = 38) after IB. Consequently, our main endpoint could not be statistically answered. Improvement of dyspnea symptoms is noticeable in each group but lasts longer in the stent group. Stents do not change the survival curve but reduce unattended bronchoscopies. In the no stent group, 19 new TB were performed with 16 stents inserted contrasting with 10 rigid bronchoscopies and 3 stents placed in the stent group. In a subgroup analysis according to the oncologic management protocol following TB (firstline treatment and other lines or palliation), the beneficial effect of stenting on obstruction recurrence was highly significant (p < 0.002), but was not observed in the naïve group, free from first-line chemotherapy. Conclusion: Silicone stent placement maintains the benefit of TB after 1 year on dyspnea score, obstruction’s recurrence, and the need for new TB. Stenting does not affect the quality of life and is suggested for patients after failure of first-line chemotherapy. It is not suggested in patients without previous oncologic treatment.

Background: Randomized clinical trials of bronchial thermoplasty (BT) were conducted in patients with a baseline FEV1 greater than 50%. There is a paucity of data regarding BT in patients with more severe obstruction, and consequently these patients are often excluded from receiving BT. The purpose of this study was to compare safety and efficacy outcomes in a large cohort of patients with an FEV1 less than 50% with those of a cohort of less obstructed patients. Methods: Consecutive patients with severe asthma were drawn from the Australian BT Registry. Patients were grouped into (1) those with a baseline prebronchodilator FEV1 % predicted 1 ≥50% (n = 36). Adverse outcomes were defined as (1) remaining in hospital longer than the planned 24-hour admission posttreatment or (2) being readmitted to hospital for any cause within 30 days of a treatment. Efficacy outcomes were evaluated 6 months after BT. Results: More severely obstructed patients were no more likely to have experienced any adverse event. Significant improvements in Asthma Control Questionnaire score, exacerbation frequency, reliever medication use, and requirement for daily oral steroids were observed in both groups, and were of a similar degree. Conclusions: This study demonstrates that BT can confidently be offered to patients with asthma with an FEV1 that is 30% to 50% of predicted without risk of more frequent or more severe adverse events, and with the expectation of the same degree of response as patients with better lung function.

Mixed apneas (MA) are characterized by absent respiratory effort and airflow in the first section of the event and respiratory effort without airflow in the last section. The pathophysiology is based on coexisting ventilatory control instability and upper airway collapsibility. Diagnostic polysomnographies (PSG) from 17 male OSA patients with/without treatment-emergent central sleep apnea (TE-CSA) were retrospectively analyzed to determine breathing pattern metrics (figure 1). TE-CSA was defined as central apnea-hypopnea index ≥10/h during positive airway pressure therapy initiation. Duty ratio (DR), a surrogate for the loop gain, was calculated as ventilatory duration/cycle duration. Conclusion: MA metrics in diagnostic PSGs differ significantly between patients with/without TE-CSA. TE-CSA patients show longer apneic durations, more frequent arousals, shorter VD and smaller DR, consistent with higher ventilatory control instability.

While antifibrotic therapy is approved for idiopathic pulmonary fibrosis (IPF) based on clinical trials, we aimed to assess the effects of such treatment under real life conditions. We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients in 20 ILD expert centers in Germany. Propensity scores were applied to account for known differences in baseline characteristics of patients with and without antifibrotic therapy. In 588 patients suitable for analysis, mean age was 69.8 ± 9.1 years, 81.0% were males. Mean duration of IPF since diagnosis was 1.8 ± 3.4 years. The mean % of predicted at baseline was 68.6 ± 18.8 for forced vital capacity (FVC) and 37.8 ± 35.4 for diffusion capacity (DLCO). During a mean follow-up of 1.2 ± 0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival was 92% vs. 78% and 76% vs. 63% for patients with vs. without antifibrotic therapy (Figure). The risk of death was 37% lower in patients with antifibrotic therapy (Hazard Ratio 0.63, 95%CI: 0.45-0.87; p=0.005). The result was robust (and remained statistically significant) on multivariable analysis. Patients on antifibrotic therapy did not statistically significantly differ in the decline of FVC and DLCO compared to patients without such treatment.

Next-generation-sequencing (NGS) from circulating (ctDNA) or tissue derived tumor DNA and PD-L1 analysis are essential for the evaluation of lung cancer. The objective was to evaluate the diagnostic value of endobronchial-ultrasound-guided transbronchial-needle-aspiration (EBUS-TBNA) from tumor and lymph nodes and ctDNA analysis compared to endobronchial forceps-biopsy (FB). 30 consecutive central lung cancer subjects (10 female, median age 66, 29 current/ex-smokers) with suspected exophytic lung cancer were included. The sequence of FB and EBUS-TBNA procedures for tissue sampling was randomized. Mediastinal lymph node tissue and blood plasma was sampled additionally. PD-L1 expression level was quantified by percent of tumor cells. Mutational analysis was performed by massively parallel sequencing, library generation by adapter-ligation and target-enrichment. NGS data could be generated in 21/23 subjects (91%), 7 small-cell-lung-cancer cases were not forwarded to NGS. Comparing primary tumor FB and EBUS-TBNA samples, the accordance regarding exon-mutation-detection was 1,371/1,380 exons (99%). However, 35% of the clinical cases showed discrepant NGS results, 24% showed different PD-L1 scores. Compared to the primary tumor findings, NGS analysis from lymph node samples and ctDNA lead to discrepant findings in only 3% and 0% of cases. FB and EBUS-TBNA samples deliver discrepant results from NGS analysis in about one third of cases and from PDL1 analysis in about a quarter of cases. There is no benefit from additional routine NGS analysis from lymph node samples and ctDNA.