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Christian Kjer Heerfordt,1 Josefin Eklöf,1 Pradeesh Sivapalan,1 Truls Sylvan Ingebrigtsen,1 Tor Biering-Sørensen,2– 4 Zitta Barrella Harboe,4,5 Jesper Koefod Petersen,6,7 Christian Østergaard Andersen,8 Jonas Bredtoft Boel,9 Anne Kathrine Bock,10 Alexander G Mathioudakis,11,12 John R Hurst,13 Shailesh Kolekar,7 Sofie Lock Johansson,14 Jette Marie Bangsborg,9 Jens Otto Jarløv,9 Ram Benny Dessau,15 Christian Borbjerg Laursen,14,16 Michael Perch,4,17 Jens-Ulrik Stæhr Jensen1,4,18 1Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, Denmark; 2Department of Cardiology, Herlev and Gentofte Hospital, Cardiovascular Non-Invasive Imaging Research Laboratory, University of Copenhagen, Copenhagen, Denmark; 3Faculty of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark; 4Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 5Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark; 6Department of Respiratory Medicine, Zealand University Hospital Naestved, Naestved, Denmark; 7Department of Pulmonary Medicine, Zealand University Hospital, Roskilde, Denmark; 8Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark; 9Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark; 10Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; 11The North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 12Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 13UCL Respiratory, University College London, London, UK; 14Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark; 15Department of Clinical Microbiology, Zealand University Hospital, Slagelse Hospital, Slagelse, Denmark; 16Institute for Clinical Research, University of Southern Denmark, Odense, Denmark; 17Department of Cardiology, Section for Lung Transplantation, Rigshospitalet, Copenhagen, Denmark; 18PERSIMUNE & CHIP: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Christian Kjer Heerfordt, Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, Denmark, Tel +4523303431, Email christian.kjer.heerfordt@regionh.dkBackground: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users.Methods: The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010– 2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses.Findings:  A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with S. pneumoniae during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of S. pneumoniae as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results.Interpretation: Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring S. pneumoniae, but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.Keywords: COPD, inhaled corticosteroids, Streptococcus pneumoniae, clinical epidemiology

Background Basic thoracic ultrasound is being used more frequently by clinicians in several settings due to its high diagnostic accuracy for many common causes of respiratory failure and dyspnoea. However, ultrasound examinations are operator-dependent, and sufficient competences are needed to obtain high sensitivity and specificity of examinations. Additionally, it is crucial for ultrasound operators to perceive the competence to interpret the images and integrate them into the patient history and other examinations. This study aims to explore and gather validity evidence for an objective structured clinical examination test of basic thoracic ultrasound competences and establish a pass/fail score. Methods An expert panel created the test which included two theoretical and five practical stations representing cases with different diagnoses that cause respiratory symptoms and which are possible to establish by basic thoracic ultrasound. Twenty-five participants with different levels of experience in basic thoracic ultrasound completed the test. Data of the test scores were used for item analysis, and exploring validity evidence was done according to Messick’s framework which is recommended. The contrasting groups' standard setting method was used to establish a pass/fail score. Results The summarised internal consistency reliability was high with a Cronbach’s alpha of 0.87. The novice group (n = 4) had a mean test score of 42 ± 10.1 points, the intermediate group (n = 8) scored 79.1 ± 8.1 points, and the experienced group (n = 13) 89.0 ± 6.2 points (one-way ANOVA, p Conclusion We developed a test for the assessment of clinical competences in basic thoracic ultrasound with solid validity evidence, and a pass/fail standard with no false positives or false negatives.

Background: Lung cancer is the leading cause of cancer-related death worldwide. Early diagnosis is crucial to increased survival rates. Radial endobronchial ultrasound (rEBUS) and electromagnetic navigation bronchoscopy (ENB) have been developed for the diagnosis of small lung lesions. The aim of this systematic review was to evaluate whether the combination of rEBUS and ENB is superior to ENB alone. Method: A systematic search was performed using MEDLINE, Embase, and Cochrane Library databases on “ENB,” and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The project was registered with PROSPERO, number CRD42020214682. Results: In total, 2,092 studies were identified through a literature search. Five studies were included in the final review. One study found that the addition of rEBUS increased diagnostic yield, while another concluded the converse. Three studies did not have significant results. Meta-analysis was not feasible due to heterogeneity and the small number of studies. Conclusion: As the current evidence on the topic is sparse and heterogeneous, it is not possible to conclude whether the addition of rEBUS to ENB has a significant impact on diagnostic yield. Further studies are needed to illuminate this question in order to ensure optimal choice of endoscopic technique as well as used time and resources. The project received funding from the Region of Southern Denmark’s PhD fund.

INTRODUCTION: Tools to quickly triage and evaluate patients with suspected COVID-19 in an emergency department (ED) can improve patient care and reduce risk of overcrowding. The aim of this study was to evaluate if lung ultrasound (LUS) may provide valuable prognostic information in adult patients suspected of COVID-19.METHODS: A prospective cohort study of adult patients in an ED was conducted. LUS was performed within one hour of the patients’ arrival; COVID-19 was defined by a respiratory syndrome coronavirus 2 RNA positive test. The primary outcome was the proportion of patients suspected of COVID-19 and normal LUS with critical outcomes during follow-up, defined as one or more of the following: need of non-invasive ventilation (NIV), invasive mechanical ventilation, intensive care unit (ICU) stay or death. Follow-up was 14 days.RESULTS: A total of 83 patients were included between 9 March and 12 April 2020. In all, 47 (57%; 95% confidence interval (CI): 45.3-67.5%) had a normal LUS, 46 (98%; 95% CI: 88.7-99.9%) of whom had no critical outcomes. A total of 36 (43%; 95% CI: 32.5-54.7%) had an abnormal LUS, eight of whom (22%; 95% CI: 10.1-39.2%) had critical outcomes. Nine (11%; 95%: CI 5.1-19.6%) had one or more critical outcomes: three on NIV, five in ICUs, four on invasive mechanical ventilation and two died. Among the 12 patients (14%; 95% CI: 7.7-23.9%) tested positive for COVID-19, 11 (92%; 95% CI: 61.5-99.8%) had an abnormal LUS.CONCLUSIONS: Among adult ED patients suspected of COVID-19, a normal LUS is associated with a low risk of critical outcomes. LUS might be considered for routine use as a prognostic tool in patients suspected of COVID-19.FUNDING: none.TRIAL REGISTRATION: not relevant.

Background Ultrasound is a focus oriented tool for differentiating among cardiopulmonary diseases. Its value in the hands of emergency physicians, with various ultrasound experience, remains uncertain. We tested the hypothesis that, in emergency department patients with signs of respiratory failure, a focused cardiopulmonary ultrasound along with standard clinical examination, performed by emergency physicians with various ultrasound experience would increase the proportion of patients with correct diagnoses at 4 hours after admission compared to standard clinical examination alone. Methods In this prospective multicenter superiority trial in Danish emergency departments we randomly assigned patients presenting with acute signs of respiratory failure to intervention or control in a 1:1 ratio by block randomization. Patients received a focused cardiopulmonary ultrasound examination within 4 hours from admission. Ultrasound results were unblinded for the treating emergency physician in the intervention group. Final diagnoses and treatment were determined by blinded review of the medical record after the patients´ discharge.Results From October 9, 2015 to April 5, 2017, we randomized 218 patients and included 211 in the final analyses. At 4 hours we found; no change in the proportion of patients with correct presumptive diagnoses; intervention 79·25% (95% CI 70·3-86·0), control 77·1% (95% CI 68·0-84·3), an increased proportion of correct treatment prescribed; intervention 79·3% (95% CI 70·3-86·0), control 65·7% (95% CI 56·0-74·3) and of patients who spent less than 1 day in hospital; intervention n=42 (39·6%; 25·8 38·4), control n=25 (23·8%; 16·5-33·0). No adverse events were reported. Conclusions Focused cardiopulmonary ultrasound added to standard clinical examination in patients with signs of respiratory failure had no impact on the diagnostic accuracy, but significantly increased the proportion of correct treatment prescribed and the proportion who spent less than 1 day in hospital.Trial registration https://clinicaltrials.gov/, number NCT 02550184.

Thoracic ultrasound is now considered an essential bedside tool in respiratory medicine. Despite this, several aspects are yet to be studied and assessed, and international consensus remains limited. With this in mind, the Guest Editors of this Monograph have selected a broad range of authors who are recognised experts, represent different specialities and use thoracic ultrasound in different settings. The result is that each chapter not only reflects expert opinion at a single site in Europe, but provides a multidisciplinary and multicentre view. Chapters include: physics and basic principles; techniques and protocols: pneumothorax; pneumonia; lung tumours; the upper abdomen; and thoracic ultrasound in newborns, infants and children.

A 79 year-old woman with disseminated ovarian cancer and recurring pleural effusions, had thoracocentesis performed with drainage of purulent pleural fluid (plf) after preceding symptoms of pneumonia. Pleural empyema was suspected. However, a plf-pH-measurement of 7.3 made this diagnose less likely. A subsequent analysis of plf revealed an elevated plf-triglyceride concentration, thus confirming chylothorax. In order to distinguish between pleural empyema and chylothorax plf-pH should be considered as a routine analysis in patients with underlying malignancy and drainage of purulent pleural fluid.

SUMMARY Jesper Rømhild Davidsen, Christian Borbjerg Laursen & Poul Henning Madsen Measuring pH in pleural fluid is valuable when identifying the cause of purulent pleural effusion Ugeskr Laeger 2012 Feb 20 [Epub ahead of print] A 79 year-old woman with disseminated ovarian cancer and recurring pleural effusions, had thoracocentesis performed with drainage of purulent pleural fluid (plf) after preceding symptoms of pneumonia. Pleural empyema was suspected. However, a plf-pH-measurement of 7.3 made this diagnose less likely. A subsequent analysis of plf revealed an elevated plftriglyceride concentration, thus confirming chylothorax. In order to distinguish between pleural empyema and chylothorax plf-pH should be considered as a routine analysis in patients with underlying malignancy and drainage of purulent pleural fluid.

In Denmark patients with pleural diseases are usually first seen by departments taking care of patients with suspected lung cancer. When "diagnostic packages" was published in 2008 by the National Board of Health a 28 days maximal time to diagnosis and a 42 days maximal time to treatment were stated for lung cancer as well as for MPM. We wanted to study how well these time frames are fulfilled for MPM. For the 5-year period 2007 to 2011, we have found 146 MPM patients in the pathology registry of Odense University Hospital. This is about 30% of all incident cases in Denmark in the period. MPM was confirmed by histology in 92% of the cases. Five patients died before the final diagnosis was known. Forty-two (30%) of 141 patients were treated by best supportive care. Two patients were lost for follow-up. In three patients therapy was initiated at progression, but in 94 patients therapy began as soon as possible after the diagnosis. Eighty-three had chemotherapy, 10 had radiotherapy, and one had resection as the first step of the treatment. For the 141 patients the median time to diagnosis was 38 days (range: 6-127 days). Only 30% of the patients were diagnosed within 28 days. The median time to therapy for the 94 patients was 58 days (range: 19 - 142 days) - 21% were treated within 42 days. Among the 77 MPM patients from our primary uptake area 42% were diagnosed within 28 days and 17 out of 54 (32%) were treated within 42 days. In the same period, 84% of patients with lung cancer from our primary uptake area were diagnosed within 28 days and 74% had started treatment within 42 days.

Background: Danish guidelines have since February 2014 recommended MR of the brain prior to curative radiotherapy in patients with NSCLC and N2-disease. More recently O'Dowd et al. [Lung Cancer 86 (2014) 185–189] have suggested MR of the brain prior to surgery no matter the stage.Aim: To study whether the introduction in 2010 of follow-up by CT of thorax and upper abdomen every three months has reduced the incidence of relapse suspected from CNS-symptoms.Results: All 827 NSCLC patients from Funen completing curative treatment from 2005 to 2013 were included. The total number of relapses found after symptoms within 24 months decreased in the 3½ years after the introduction of CT-based follow-up, p < 0,001 (table), but the total fraction presenting with CNS-symptoms did not change, p = 0.296. Relapses after stage I cancer decreased (p = 0.025), while no differences or changes for stages II or III were found.Conclusion: CT-based follow-up has not reduced the incidence of relapse suspected from CNS-symptoms in stage II-IV, and therefore we suggest routine MR of the brain before curative treatment for this group of patients.Number, fractions(%), and [95%CI]Jan. 2005 - June 2010July 2010 - Dec. 2013Patients with intended curative treatment449378Relapse within 24 months172 (38.3%) [33.8-43.0%]155 (41.0%) [36.0-46.2%]Relapse suspected from symptoms118 (26.3%) [22.3-30.6%]49 (13.0%) [9.8-16.8%]Relapse suspected from CNS-symptoms30 (6.7%) [4.6-9.4%]18 (4.8%) [2.9-7.4%]- Stage I9 (4.1%) [1.9-7.7%]1 (0.6%) [0.0-3.0%]- Stage II7 (7.0%) [2.9-13.9%]6 (6.7%) [2.5-14.1%]- Stage III13 (10.7%) [5.8-17.5%]8 (9.0%) [4.0-17.0%]- Stage IV - with initial brain metastases1 (16.7%) [4.2-64.1%]3 (50.0%) [11.8-88.2%]

The use of one single ultrasound echoendoscope in both the trachea (EBUS) and the oesophagus (EUS-B) gives a fast, safe and precise diagnosis and stage of the patient with suspected lung cancer. There is solid evidence for simulator-based training in EBUS concerning safety and diagnostic outcome, but this is currently not an option in EUS-B and needs development. In this review, we recommend evidence-based simulator training and certification in EBUS and when available also in EUS-B before practicing on patients.

Introduction In this case report we describe how pneumoperitoneum was diagnosed in a patient admitted with acute chest pain, as an incidental finding using focus assessed transthoracic echocardiography (FATE). Case report A 79-year-old male smoker with arterial hypertension was admitted to a coronary unit with a sudden onset of constant left sided thoracic pain. At position 1 (subcostal) of the FATE protocol, the heart and liver could not be visualised. Instead the peritoneum could be seen as a hyperechoic stripe, corresponding horizontal reverberation artefacts was visible under the peritoneal line. Based on these findings, a conventional X-ray image of the abdomen was taken with the patient in the left lateral decubitus position, confirming the diagnosis of pneumoperitoneum. Conclusion This demonstrates how systematic use of FATE combined with knowledge of sonographic patterns in extracardial diseases can directly ensure the patients a quicker diagnosis and treatment.