Bronchoscopic procedures to diagnose peripheral lung lesions.

Bronchoscopy has a low risk of complications when diagnosing peripheral lung lesions suspected of malignancy, however the procedures do not always determine a diagnosis. Several modalities have been invented to improve the diagnostic yield, including radial endobronchial ultrasound and electromagnetic navigation, which are currently used by several departments in Denmark. Augmented fluoroscopy, CT-guided bronchoscopy and robotic bronchoscopy are not yet available in Denmark, but may improve the diagnostic work-up, as argued in this review.

Diaphragmatic dysfunction is associated with postoperative pulmonary complications and phrenic nerve paresis in patients undergoing thoracic surgery.

PURPOSE: We aimed to quantify perioperative changes in diaphragmatic function and phrenic nerve conduction in patients undergoing routine thoracic surgery. METHODS: A prospective observational study was performed in patients undergoing esophageal resection or pulmonary lobectomy. Examinations were carried out the day prior to surgery, 3 days and 10-14 days after surgery. Endpoints for diaphragmatic function included ultrasonographic measurements of diaphragmatic excursion and thickening fraction. Endpoints for phrenic nerve conduction included baseline-to-peak amplitude, peak-to-peak amplitude, and transmission delay. Measurements were assessed on both the surgical side and the non-surgical side of the thorax. RESULTS: Forty patients were included in the study. Significant reductions in diaphragmatic excursion were seen on the surgical side of the thorax for all excursion measures (posterior part of the right hemidiaphragm, p < 0.001; hemidiaphragmatic top point, p < 0.001; change in intrathoracic area, p < 0.001). Significant changes were seen for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.041) on the surgical side. However, significant changes were also seen on the non-surgical side for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.022). A postoperative reduction in posterior diaphragmatic excursion of more than 50% was significantly associated with postoperative pulmonary complications (coefficient: 2.69 (95% CI [1.38, 4.01], p < 0.001). CONCLUSION: Thoracic surgery caused a significant unilateral reduction in diaphragmatic excursion on the surgical side of the thorax, which was accompanied by significant changes in phrenic nerve conduction. However, phrenic nerve conduction was also significantly affected on the non-surgical side to a lesser extent, which was not mirrored in diaphragmatic excursion. Our findings suggest that phrenic nerve paresis plays a role in postoperative diaphragmatic dysfunction, which may be a contributing factor in the pathogenesis of postoperative pulmonary complications. CLINICAL TRIALS REGISTRATION NUMBER: NCT04507594.

National survey on management of spontaneous pneumothorax from emergency department to specialised treatment: room for improvement.

Introduction: Spontaneous pneumothorax (SP) affects both young, otherwise healthy individuals and older persons with known underlying pulmonary disease. Initial management possibilities are evolving and range from observation to chest tube insertion. SP guidelines suggest an individualized approach based on multiple factors such as symptoms, size of pneumothorax, comorbidity and patient preference. Aim: With this Danish national survey we aimed to map organization of care including involved specialties, treatment choice, training, and follow-up plans to identify aspects, and optimization of spontaneous pneumothorax management. Method: A survey developed by the national interest group for pleural medicine was sent to all departments of emergency medicine, thoracic surgery, respiratory medicine, and to relevant departments of abdominal or orthopaedic surgery. Results: The response rate was 75 % (47 of 65). Overall, 21% of responding departments had no guideline for SP management, which was provided by multiple specialties with marked heterogeneity in choice of treatment including tube size, management during admission, and referral procedure to follow-up. Few departments required procedure training, and nearly all of the responders called for improvements in management of pneumothorax. Conclusion: This survey suggests that SP management and care is delivered heterogeneously across Danish hospitals with marked difference between respiratory physicians, emergency physicians, general surgeons and thoracic surgeons. It is therefore likely that management is sub-optimal. There is a need for a common Danish SP guideline to ensure optimal treatment across involved specialties.

Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Diseases and Peripheral Pulmonary Lesions - A Stepwise Approach.

Transbronchial lung cryobiopsy (TBLC) is an invasive procedure increasingly implemented during the last decade as an alternative to video-assisted thoracic surgery lung biopsy (SLB) for diagnosing interstitial lung diseases (ILDs). The indication for TBLC has primarily been to sub-classify a specific ILD subtype when this cannot be achieved on the basis of a preceding multidisciplinary team discussion. Although SLB is considered the gold standard for establishing a histological diagnosis, TBLC has been gradually suggested as the first-choice histological diagnostic modality in patients with unclassified ILDs due to a comparable diagnostic yield with SLB, but superior to SLB in terms of complications, including mortality. During recent years, radial endobronchial ultrasound (R-EBUS) and electromagnetic navigation bronchoscopy (ENB)-guided TBLC for peripheral pulmonary lesions have also been described as safe procedures, which may improve the diagnostic yield compared to forceps biopsies. Still, the diagnostic properties of TBLC rely on the quality of the procedure's performance. This article aims to describe the stepwise approach to conducting TBLC with a flexible bronchoscope for the different indications mentioned, which might be helpful for novice bronchoscopists performing TBLC.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

INTRODUCTION: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. METHODS AND ANALYSIS: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. ETHICS AND DISSEMINATION: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www. CLINICALTRIALS: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: NCT04095676.

The CRISPR/Cas9 Minipig-A Transgenic Minipig to Produce Specific Mutations in Designated Tissues.

The generation of large transgenic animals is impeded by complex cloning, long maturation and gastrulation times. An introduction of multiple gene alterations increases the complexity. We have cloned a transgenic Cas9 minipig to introduce multiple mutations by CRISPR in somatic cells. Transgenic Cas9 pigs were generated by somatic cell nuclear transfer and were backcrossed to Göttingen Minipigs for two generations. Cas9 expression was controlled by FlpO-mediated recombination and was visualized by translation from red to yellow fluorescent protein. In vitro analyses in primary fibroblasts, keratinocytes and lung epithelial cells confirmed the genetic alterations executed by the viral delivery of single guide RNAs (sgRNA) to the target cells. Moreover, multiple gene alterations could be introduced simultaneously in a cell by viral delivery of sgRNAs. Cells with loss of TP53, PTEN and gain-of-function mutation in KRASG12D showed increased proliferation, confirming a transformation of the primary cells. An in vivo activation of Cas9 expression could be induced by viral delivery to the skin. Overall, we have generated a minipig with conditional expression of Cas9, where multiple gene alterations can be introduced to somatic cells by viral delivery of sgRNA. The development of a transgenic Cas9 minipig facilitates the creation of complex pre-clinical models for cancer research.

Barriers toward Physical Activity in COPD: A Quantitative Cross-Sectional, Questionnaire-Based Study.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive but preventable and treatable disease and the third leading cause of death globally. Even though it is evident that physical activity (PA) relieves dyspnea, anxiety, fatigue, and increases quality of life and functional capacity, it is seldom implemented in daily life in people with COPD. The aim of this study was to identify barriers toward PA in people with COPD and to examine the role of FEV1 and smoking status in PA. The study is a quantitative cross-sectional study conducted in Denmark among people with COPD. Data was collected using questionnaires developed by the authors after pilot testing. In total, 493 people with COPD were included. The most significant barrier toward PA was low motivation (p < 0,001 and p = 0,009) and comorbidity (p = 0,035 and p = 0,016). Fear of breathlessness was significantly (p < 0,001) correlated to low motivation. FEV1, and smoking status were not associated with the level of PA. In our study, the main reason why people with COPD did not engage in PA was low motivation, where fear of breathlessness and co-morbidity correlated significantly with low motivation. Studies have shown that doing activities that are enjoyable promotes PA in daily life, indicating that activities that enhance motivation might help people with COPD to see PA as part of their life rather than an obligation. Further exploratory studies are needed.

[Malignant pleural effusion].

Malignant pleural effusion (MPE) is a common condition, often associated with a high level of symptoms. In this review, several palliative treatments for symptomatic MPE are summarised, including repeated thoracentesis, pleurodesis and insertion of indwelling pleural catheters. Choice of treatment depends on patient symptoms, life expectancy, pleural fluid production, expected effect of oncological treatment, whether trapped lung is suspected or not, and patient preferences. Treatment should be discussed with a pulmonary specialist with knowledge of pleural diseases.

SARS-CoV-2 evades immune detection in alveolar macrophages.

Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.

[Medical thoracoscopy in the elucidationof recurrent pleural effusion].

Medical thoracoscopy allows the respiratory physician access to inspection and biopsy of the pleura. The method has several names, such as pleuroscopy, non-intubated thoracoscopy and exploratory thoracoscopy, all of which cover the same procedure. The main indication for medical thoracoscopy is the diagnosis of recurrent pleural effusion, where pleural biopsy is needed. Medical thoracoscopy differs from thoracic surgical surgery as patients are sedated rather than in general anaesthesia. This is a review of the state of the art of pulmonological investigations of recurrent pleural effusion and the important role of medical thoracoscopy.

Ultrasound-assisted aspiration of loculated pneumothorax: A new technique.

In this report, we describe a new sonographic (US) technique that can assist in the aspiration of a loculated pneumothorax. Patients may develop loculated pneumothorax as a result of such conditions as pleural malignancy or pleural infection or after undergoing thoracic surgery. Often the loculated pneumothorax is outside of safe areas, and chest tubes need to be placed near vital structures. This report presents the cases of three patients with iatrogenic loculated pneumothorax that required aspiration. We used US to assist in the placement of chest tubes, and we describe our technique of US-assisted aspiration of loculated pneumothorax. The procedure is a new approach to a common problem in chest medicine that may increase the safety of treatment. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:326-330, 2016.