[Outpatient care in pulmonology - a scientific analysis and a position paper of the German Society of Respiratory Medicine (DGP)]. / Ambulantisierung in der Pneumologie ­ eine wissenschaftliche Analyse und ein Positionspapier der DGP.

INTRODUCTION: The ambulantization of patient care that were previously provided as inpatient service is one of the goals of the current reform in the German healthcare system. In pulmonology, this particularly applies to endoscopic procedures. However, the real costs of endoscopic services, which form the basis for the calculation of a future so called hybrid DRG or in the AOP catalog, are unclear. METHODS: After selection of use cases including endoscopic procedures which can be performed on an outpatient basis by a committee of experts the appropriate DRGs were identified from the §â€Š21-KHEntgG data for 2022 published by the Institute for the Hospital Remuneration System (InEK). The costs were calculated from the respective InEK cost matrix added by the calculated material costs. RESULTS: The use cases suitable for outpatient treatment were systematic endobronchial ultrasound (EBUS) with transbronchial needle aspiration (calculated costs €â€Š2,175.60 without or €â€Š3,315.60 including PET/CT), navigation-assisted bronchoscopy for peripheral lesions (depending on the methodology €â€Š2,870.23 to €4,120.23) and diagnostic (flexible) bronchoscopy (€â€Š1,121.02). CONCLUSION: Outpatient treatment of endoscopic procedures that were previously performed inpatient is possible and necessary, and the costs calculated in this publication can form a reliable basis for appropriate reimbursement. Together with a structural quality that has been transformed to outpatient service and cross-sector cooperation, continued high-quality care for pneumological patients can be ensured.

Causes and Risk Factors for Absenteeism among Medical Staff in German Specialized Lung Clinics during the COVID Pandemic.

BACKGROUND: Staff shortages pose a major challenge to the health system. OBJECTIVES: The objective of this study was to clarify the role of different causative factors we investigated on staff absenteeism during the COVID pandemic. METHODS: The prospective multicentre cohort study assessed the private and professional impact of the pandemic on health care workers (HCWs) using a specially developed questionnaire. HCWs from 7 specialist lung clinics throughout Germany were surveyed from December 1 to December 23, 2021. The current analysis addresses pandemic-related absenteeism. RESULTS: 1,134 HCW (55% female; 18.4% male, 26.3% not willing to provide information on age or gender) participated. 72.8% had received at least one vaccination dose at the time of the survey, and 9.4% reported a COVID infection. Of those with positive tests, 98% reported home quarantine for median (IQR) 14 (12-17) days; 10.3% of those who ultimately tested negative also reported quarantine periods of 14 (7-14) days. 32.2% of vaccinated respondents reported absenteeism due to vaccine reactions of 2 (1-3) days. Overall, 37% (n = 420) of HCW reported pandemic-related absenteeism, with 3,524 total days of absenteeism, of which 2,828 were due to illness/quarantine and 696 to vaccination effects. Independent risk factors for COVID-related absenteeism ≥5 days included already having COVID, but also concern about long-term effects of COVID (OR 1,782, p = 0.014); risk factors for vaccine-related absenteeism ≥2 days included concerns of late effects of vaccination (OR 2.2, 95% CI: 1.4-3.1, p < 0.000). CONCLUSION: Staff shortages due to quarantine or infections and vaccine reactogenicity have put a strain on German respiratory specialists. The fact that staff concerns also contributed to absenteeism may be helpful in managing future pandemic events to minimize staff absenteeism.

Gender Differences in Health Care Workers' Risk-Benefit Trade-Offs for COVID-19 Vaccination.

BACKGROUND: Gender differences in vaccine acceptance among health care workers (HCWs) are well documented, but the extent to which these depend on occupational group membership is less well studied. We aimed to determine vaccine acceptance and reasons of hesitancy among HCWs of respiratory clinics in Germany with respect to gender and occupational group membership. METHODS: An online questionnaire for hospital staff of all professional groups was created to assess experiences with and attitudes towards COVID-19 and the available vaccines. Employees of five clinics were surveyed from 15 to 28 March 2021. RESULTS: 962 employees (565 [72%] female) took part in the survey. Overall vaccination acceptance was 72.8%. Nurses and physicians showed greater willingness to be vaccinated than members of other professions (72.8%, 84.5%, 65.8%, respectively; p = 0.006). In multivariate analyses, worries about COVID-19 late effects (odds ratio (OR) 2.86; p < 0.001) and affiliation with physicians (OR 2.20; p = 0.025) were independently associated with the willingness for vaccination, whereas age <35 years (OR 0.61; p = 0.022) and worries about late effects of vaccination (OR 0.13; p < 0.001) predicted vaccination hesitancy; no differences were seen with respect to gender. In separate analyses for men and women, only for men worries about COVID-19 late effects were relevant, while among women, age <35 years, worries about late effects of vaccination and worries about COVID-19 late effects played a role. CONCLUSIONS: There was no overall difference in vaccination acceptance between male and female HCWs, but there were gender-specific differences in the individual reasons on which this decision-making was based.

Crossover Patient Outcomes for Targeted Lung Denervation in Moderate to Severe Chronic Obstructive Pulmonary Disease: AIRFLOW-2.

BACKGROUND: Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. OBJECTIVES: This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. METHOD: The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30-60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. RESULTS: Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, p = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227, not statistically significant). Symptom scores and lung function showed stability. CONCLUSIONS: AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD.

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

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

Mediastinales Staging.

Thorough mediastinal staging is pivotal for prognostic assessment and treatment planning in patients with non-small-cell lung cancer (NSCLC) without distant metastasis. It aims to answer the question of whether a technically and functionally feasible operation also makes sense from an oncological point of view. In case of a nodal-free mediastinum, primary surgical therapy can be considered. If the ipsilateral mediastinal lymph nodes are affected, multimodal therapy should be sought. Operating is usually no longer the first step, especially with extensive lymph node infestation. Surgery is recommended, if neoadjuvant (radio-)chemotherapy has achieved downstaging or major response. If the contralateral mediastinal lymph nodes are involved, curative surgery is no longer part of the therapeutic concept. The therapy of choice in this situation is definitive chemo-radiotherapy.Guidelines for mediastinal staging consistently require to combine radiological, nuclear medicine and minimally invasive methods. Imaging with CT and PET allows an initial assessment of the mediastinal status. In most cases it has to be complemented with tissue confirmation. Echoendoscopic assessment of the mediastinum with needle biopsy is the minimally invasive method of first choice ("needle first"). Surgical staging methods are reserved for situations, that cannot be satisfactorily clarified by echoendoscopy.Technique and outcome of the different methods are described and algorithms are presented for different oncological situations.

[Mediastinal Staging]. / Mediastinales Staging.

Thorough mediastinal staging is pivotal for prognostic assessment and treatment planning in patients with non-small-cell lung cancer (NSCLC) without distant metastasis. It aims to answer the question of whether a technically and functionally feasible operation also makes sense from an oncological point of view. In case of a nodal-free mediastinum, primary surgical therapy can be considered. If the ipsilateral mediastinal lymph nodes are affected, multimodal therapy should be sought. Operating is usually no longer the first step, especially with extensive lymph node infestation. Surgery is recommended, if neoadjuvant (radio-)chemotherapy has achieved downstaging or major response. If the contralateral mediastinal lymph nodes are involved, curative surgery is no longer part of the therapeutic concept. The therapy of choice in this situation is definitive chemo-radiotherapy.Guidelines for mediastinal staging consistently require to combine radiological, nuclear medicine and minimally invasive methods. Imaging with CT and PET allows an initial assessment of the mediastinal status. In most cases it has to be complemented with tissue confirmation. Echoendoscopic assessment of the mediastinum with needle biopsy is the minimally invasive method of first choice ("needle first"). Surgical staging methods are reserved for situations, that cannot be satisfactorily clarified by echoendoscopy.Technique and outcome of the different methods are described and algorithms are presented for different oncological situations.

Screening for Bronchoscopic Lung Volume Reduction: Reasons for Not Receiving Interventional Treatment.

BACKGROUND: Evidence for bronchoscopic lung volume reduction (BLVR) is based on phase 2 studies and small randomized controlled trials with in- and exclusion criteria defining a therapeutic window and contraindications. Little is known about the applicability in routine clinical practice. AIM: Which percentage of patients with severe emphysema referred to a specialized treatment center for BLVR is ultimately suitable for interventional bronchoscopic treatment? What is the relevance of the different contraindications? METHODS: Retrospective evaluation of emphysema patients referred to Asklepios Fachkliniken Munich-Gauting for BLVR between January 2014 and June 2015. RESULTS: 138 patients were referred for evaluation of BLVR. 38 patients (27.5%) underwent BLVR procedures (valves n = 18; coils n = 18; thermal vapor ablation n = 2). 100 patients (72.5%) were deemed not eligible for BLVR based on the following contraindications: 34% emphysema morphology and emphysema-related findings (severe homogeneous emphysema, extensive pleuropulmonary adhesions, postinflammatory scaring with natural volume reduction, giant bullae), 16% active smoking; 9% pulmonary function not within indication range; 8% unexpected CT findings (nodules, cancer, interstitial disease); 8% chronic ventilatory failure; 8% patient refused BLVR; 5% relevant comorbidity; 5% frequent exacerbations, 3% preserved quality of life, 4% other. CONCLUSION: BLVR is a therapeutic option for highly selected patients. In our cohort, one in four could be treated. These data highlight the limitations of BLVR under real-life conditions.

Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial.

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).

Bleeding risk of transbronchial cryobiopsy compared to transbronchial forceps biopsy in interstitial lung disease - a prospective, randomized, multicentre cross-over trial.

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 < 0.001). The rate of clinically relevant bleeding (moderate or severe) was higher after the cryobiopsy procedures compared to the forceps biopsies (16.2% vs. 4.2%, p < 0.05). No fatal bleeding complications occurred. CONCLUSIONS: Compared to transbronchial forceps biopsy, transbronchial cryobiopsy was associated with an increased risk of bleeding which is of clinical relevance. Therefore training and additional precautions for bleeding control should be considered. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov ( NCT01894113 ).

Management of Spontaneous Pneumothorax and Post-Interventional Pneumothorax: German S3 Guideline.

In Germany, 10,000 cases of spontaneous pneumothorax are treated inpatient every year. The German Society for Thoracic Surgery, in co-operation with the German Society for Pulmonology, the German Radiological Society, and the German Society of Internal Medicine has developed an S3 guideline on spontaneous pneumothorax and post-interventional pneumothorax moderated by the German Association of Scientific Medical Societies. METHOD: Based on the source guideline of the British Thoracic Society (2010) for spontaneous pneumothorax, a literature search on spontaneous pneumothorax was carried out from 2008 onwards, for post-interventional pneumothorax from 1960 onwards. Evidence levels according to the Oxford Center for Evidence-Based Medicine (2011) were assigned to the relevant studies found. Recommendations according to grade (A: "we recommend"/"we do not recommend," B: "we suggest"/"we do not suggest") were determined in 3 consensus conferences by the nominal group process. RESULTS: The algorithms for primary and secondary pneumothorax differ in the indication for CT scan as well as in the indication for chest drainage application and video-assisted thoracic surgery. Indication for surgery is recommended individually taking into account the risk of recurrence, life circumstances, patient preferences, and procedure risks. For some forms of secondary pneumothorax, a reserved indication for surgery is recommended. Therapy of post-interventional spontaneous pneumothorax is similar to that of primary spontaneous pneumothorax. DISCUSSION: The recommendations of the S3 Guideline provide assistance in managing spontaneous pneumothorax and post-interventional pneumothorax. Whether this will affect existing deviant diagnostic and therapeutic measures will be demonstrated by future epidemiological studies.

Increased Extracellular Vesicles Mediate WNT5A Signaling in Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by lung epithelial cell injury, increased (myo)fibroblast activation, and extracellular matrix deposition. Extracellular vesicles (EVs) regulate intercellular communication by carrying a variety of signaling mediators, including WNT (wingless/integrated) proteins. The relevance of EVs in pulmonary fibrosis and their potential contribution to disease pathogenesis, however, remain unexplored.Objectives: To characterize EVs and study the role of EV-bound WNT signaling in IPF.Methods: We isolated EVs from BAL fluid (BALF) from experimental lung fibrosis as well as samples from IPF, non-IPF interstitial lung disease (ILD), non-ILD, and healthy volunteers from two independent cohorts. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Primary human lung fibroblasts (phLFs) were used for EV isolation and analyzed by metabolic activity assays, cell counting, quantitative PCR, and Western blotting upon WNT gain- and loss-of-function studies.Measurements and Main Results: We found increased EVs, particularly exosomes, in BALF from experimental lung fibrosis as well as from patients with IPF. WNT5A was secreted on EVs in lung fibrosis and induced by transforming growth factor-ß in primary human lung fibroblasts. The phLF-derived EVs induced phLF proliferation, which was attenuated by WNT5A silencing and antibody-mediated inhibition and required intact EV structure. Similarly, EVs from IPF BALF induced phLF proliferation, which was mediated by WNT5A.Conclusions: Increased EVs function as carriers for signaling mediators, such as WNT5A, in IPF and thus contribute to disease pathogenesis. Characterization of EV secretion and composition may lead to novel approaches to diagnose and develop treatments for pulmonary fibrosis.

Management of Spontaneous Pneumothorax and Postinterventional Pneumothorax: German S3-Guideline. / S3-Leitlinie: Diagnostik und Therapie von Spontanpneumothorax und postinterventionellem Pneumothorax.

In Germany, 10,000 cases of spontaneous pneumothorax are treated inpatient every year. The German Society for Thoracic Surgery (DGT), in co-operation with the German Society for Pulmonology (DGP), the German Radiological Society (DRG) and the German Society of Internal Medicine (DGIM) has developed an S3 guideline on spontaneous pneumothorax and postinterventional pneumothorax moderated by the German Association of Scientific Medical Societies (AWMF). METHOD: Based on the source guideline of the British Thoracic Society (BTS2010) for spontaneous pneumothorax, a literature search on spontaneous pneumothorax was carried out from 2008 onwards, for post-interventional pneumothorax from 1960 onwards. Evidence levels according to the Oxford Center for Evidence-Based Medicine (2011) were assigned to the relevant studies found. Recommendations according to GRADE (A: "we recommend"/"we do not recommend", B: "we suggest"/"we do not suggest") were determined in three consensus conferences by the nominal group process. RESULTS: The algorithms for primary and secondary pneumothorax differ in the indication for CT scan as well as in the indication for chest drainage application and video-assisted thoracic surgery (VATS). Indication for surgery is recommended individually taking into account the risk of recurrence, life circumstances, patient preferences and procedure risks. For some forms of secondary pneumothorax, a reserved indication for surgery is recommended. Therapy of postinterventional spontaneous pneumothorax is similar to that of primary spontaneous pneumothorax. DISCUSSION: The recommendations of the S3 Guideline provide assistance in managing spontaneous pneumothorax and post-interventional pneumothorax. Whether this will affect existing deviant diagnostic and therapeutic measures will be demonstrated by future epidemiological studies.

slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation.

Human monocytes are subdivided into classical, intermediate, and nonclassical subsets, but there is no unequivocal strategy to dissect the latter 2 cell types. We show herein that the cell surface marker 6-sulfo LacNAc (slan) can define slan-positive CD14(+)CD16(++) nonclassical monocytes and slan-negative CD14(++)CD16(+) intermediate monocytes. Gene expression profiling confirms that slan-negative intermediate monocytes show highest expression levels of major histocompatibility complex class II genes, whereas a differential ubiquitin signature is a novel feature of the slan approach. In unsupervised hierarchical clustering, the slan-positive nonclassical monocytes cluster with monocytes and are clearly distinct from CD1c(+) dendritic cells. In clinical studies, we show a selective increase of the slan-negative intermediate monocytes to >100 cells per microliter in patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor mutations. These data demonstrate that the slan-based definition of CD16-positive monocyte subsets is informative in molecular studies and in clinical settings.

Collapse phenomenon during Chartis collateral ventilation assessment.

Chartis is increasingly used for bronchoscopic assessment of collateral ventilation before endobronchial valve (EBV) treatment for severe emphysema. Its prognostic value is, however, limited by the airway collapse phenomenon. The frequency and clinical significance of the collapse phenomenon remain largely unknown.We performed a retrospective analysis of 92 patients undergoing Chartis evaluation under spontaneous breathing (n=55) or jet ventilation (n=37) from May 2010 to November 2013. Collateral ventilation status (positive/negative/collapse phenomenon/unclear) was reassessed and correlated with high-resolution computed tomography (HRCT) fissure analysis and clinical response.In the absence of the collapse phenomenon, the predictive value of Chartis measurements and HRCT fissural analysis was comparable. The collapse phenomenon was observed in 31.5% of all assessments, and was more frequent in lower lobes (44.9% versus 16.9% in upper lobes) and under jet ventilation (41.4% versus 22.1% under spontaneous breathing). 69.8% of lobes with the collapse phenomenon had complete fissures. Most patients with the collapse phenomenon in the target lobe and complete fissures treated with EBVs were responders (n=11/15). All valve-treated collapse phenomenon patients with fissure defects were nonresponders (n=3).In the absence of the collapse phenomenon Chartis measurement is reliable to predict response to valve treatment. In patients with the collapse phenomenon, treatment decisions should be based on HRCT detection of fissure integrity. Chartis assessment should be performed under spontaneous breathing.

Patterns of Emphysema Heterogeneity.

BACKGROUND: Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. OBJECTIVE: The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. METHODS: Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. RESULTS: Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥30% difference in tissue destruction. CONCLUSION: Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones.

Bronchoscopic Coil Treatment for Patients with Severe Emphysema: A Meta-Analysis.

BACKGROUND: Bronchoscopic coil treatment has been shown to improve pulmonary function, exercise capacity, and quality of life in patients with severe emphysema. OBJECTIVES: To perform a meta-analysis of the results of four independent European clinical trials investigating this coil therapy for emphysema. METHODS: Data on all patients included in the four European clinical trials were analyzed for efficacy and safety outcomes. RESULTS: A total of 2,536 coils were placed during 259 procedures in 140 patients. A total of 37 chronic obstructive pulmonary disease exacerbations and 27 pneumonias were recorded as serious adverse events up to 1 year after treatment. The pneumothorax rate was 6.4%. Both 6 and 12 months after treatment, significant (all p < 0.001) improvements were observed for: forced expiratory volume in 1 s [+0.08 liters (±0.19) and +0.08 liters (±0.21)], residual volume [RV; -510 ml (±850) and -430 ml (±720)], 6-min walking distance [6MWD; +44.1 m (±69.8) and +38.1 m (±71.9)], and St. George's Respiratory Questionnaire score [SGRQ; -9.5 points (±14.3) and -7.7 points (±14.2)]. No differences in any outcome measures were observed between heterogeneous and homogeneous emphysema patients. Only a high baseline RV was found to be an independent predictor of successful treatment. CONCLUSIONS: Bronchoscopic coil treatment improves pulmonary function, 6MWD, and quality of life in patients with severe emphysema up to 1 year after treatment, independent of the distribution of the disease.

Lung volume reduction coil treatment for patients with severe emphysema: a European multicentre trial.

BACKGROUND: The lung volume reduction (LVR) coil is a minimally invasive bronchoscopic nitinol device designed to reduce hyperinflation and improve elastic recoil in severe emphysema. We investigated the feasibility, safety and efficacy of LVR coil treatment in a prospective multicentre cohort trial in patients with severe emphysema. METHODS: Patients were treated in 11 centres. Safety was evaluated by recording all adverse events, efficacy by the St George's Respiratory Questionnaire (SGRQ) as primary endpoint, and pulmonary function testing, modified Medical Research Council dyspnoea score (mMRC) and 6-min walk distance (6MWD) up to 12 months after the final treatment. RESULTS: Sixty patients (60.9 ± 7.5 years, forced expiratory volume in 1 s (FEV(1)) 30.2 ± 6.3% pred) were bronchoscopically treated with coils (55 bilateral, 5 unilateral), with a median of 10 (range 5-15) coils per lobe. Within 30 days post-treatment, seven chronic obstructive pulmonary disease exacerbations (6.1%), six pneumonias (5.2%), four pneumothoraces (3.5%) and one haemoptysis (0.9%) occurred as serious adverse events. At 6 and 12 months, respectively, ΔSGRQ was -12.1±12.9 and -11.1±13.3 points, Δ6MWD was +29.7±74.1 m and +51.4±76 m, ΔFEV(1) was +0.11±0.20 L and +0.11±0.30 L, and ΔRV (residual volume) was -0.65±0.90 L and -0.71±0.81 L (all p<0.01). Post hoc analyses showed significant responses for SGRQ, 6MWD and RV in patients with both heterogeneous and homogeneous emphysema. CONCLUSIONS: LVR coil treatment results in significant clinical improvements in patients with severe emphysema, with a good safety profile and sustained results for up to 1 year. TRIAL REGISTRATION NUMBER: NCT01328899.

Assessment of efficacy and safety of endoscopic lung volume reduction with one-way valves in patients with a very low FEV1.

Introduction: Endoscopic lung volume reduction (ELVR) with one-way valves produces beneficial outcomes in patients with severe emphysema. Evidence on the efficacy remains unclear in patients with a very low forced expiratory volume in 1 s (FEV1) (≤20% predicted). We aim to compare clinical outcomes of ELVR, in relation to the FEV1 restriction. Methods: All data originated from the German Lung Emphysema Registry (Lungenemphysem Register), which is a prospective multicentric observational study for patients with severe emphysema after lung volume reduction. Two groups were formed at baseline: FEV1 ≤20% pred and FEV1 21-45% pred. Pulmonary function tests (FEV1, residual volume, partial pressure of carbon dioxide), training capacity (6-min walk distance (6MWD)), quality of life (modified Medical Research Council dyspnoea scale (mMRC), COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ)) and adverse events were assessed and compared at baseline and after 3 and 6 months. Results: 33 patients with FEV1 ≤20% pred and 265 patients with FEV1 21-45% pred were analysed. After ELVR, an increase in FEV1 was observed in both groups (both p<0.001). The mMRC and CAT scores, and 6MWD improved in both groups (all p<0.05). The SGRQ score improved significantly in the FEV1 21-45% pred group, and by trend in the FEV1 ≤20% pred group. Pneumothorax was the most frequent complication within the first 90 days in both groups (FEV1 ≤20% pred: 7.7% versus FEV1 21-45% pred: 22.1%; p=0.624). No deaths occurred in the FEV1 ≤20% pred group up to 6 months. Conclusion: Our study highlights the potential efficacy of one-way valves, even in patients with very low FEV1, as these patients experienced significant improvements in FEV1, 6MWD and quality of life. No death was reported, suggesting a good safety profile, even in these high-risk patients.

Higher in-hospital mortality in SARS-CoV-2 omicron variant infection compared to influenza infection-Insights from the CORONA Germany study.

BACKGROUND: With the emergence of new subvariants, the disease severity of Severe Acute Respiratory Syndrome Coronavirus-2 has attenuated. This study aimed to compare the disease severity in patients hospitalized with omicron variant infection to those with influenza infection. METHODS: We compared data from the multicenter observational, prospective, epidemiological "CORONA Germany" (Clinical Outcome and Risk in hospitalized COVID-19 patients) study on patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 to retrospective data on influenza infection cases from November 2016 to August 2022. Severe Acute Respiratory Syndrome Coronavirus-2 cases were classified as wild-type/delta variant before January 2022, or omicron variant from January 2022 onward. The primary outcome was in-hospital mortality, adjusted for age, gender, and comorbidities. RESULTS: The study included 35,806 patients from 53 hospitals in Germany, including 4,916 patients (13.7%) with influenza infection, 16,654 patients (46.5%) with wild-type/delta variant infection, and 14,236 patients (39.8%) with omicron variant infection. In-hospital mortality was highest in patients with wild-type/delta variant infection (16.8%), followed by patients with omicron variant infection (8.4%) and patients with influenza infection (4.7%). In the adjusted analysis, higher age was the strongest predictor for in-hospital mortality (age 80 years vs. age 50 years: OR 4.25, 95% CI 3.10-5.83). Both, patients with wild-type/delta variant infection (OR 3.54, 95% CI 3.02-4.15) and patients with omicron variant infection (OR 1.56, 95% CI 1.32-1.84) had a higher risk for in-hospital mortality than patients with influenza infection. CONCLUSION: After adjusting for age, gender and comorbidities, patients with wild-type/delta variant infection had the highest risk for in-hospital mortality compared to patients with influenza infection. Even for patients with omicron variant infection, the adjusted risk for in-hospital mortality was higher than for patients with influenza infection. The adjusted risk for in-hospital mortality showed a strong age dependency across all virus types and variants. TRIAL REGISTRATION NUMBER: NCT04659187.