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Andreas Horner,1 Horst Olschewski,2 Sylvia Hartl,3 Arschang Valipour,4 Georg-Christian Funk,5 Michael Studnicka,6 Monika Merkle,7 Bernhard Kaiser,1 Eva Maria Wallner,8 Stephan Brecht,8 Bernd Lamprecht1 1Johannes Kepler University Linz, Kepler University Hospital, Department of Pulmonology, Linz, Austria; 2Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, and Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; 3Department of Respiratory and Critical Care Medicine, Klinik Penzing and Sigmund Freud University, Medical School, Vienna, Austria; 4Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria; 5Department of Internal and Respiratory Medicine, Klinik Ottakring, Vienna, Austria; 6Department of Pulmonary Medicine, Paracelsus Medical University, Salzburg, Austria; 7Specialist Office for Pulmonology Dr. Merkle, Vienna, Austria; 8A. Menarini Pharma GmbH, Vienna, AustriaCorrespondence: Andreas Horner, Johannes Kepler University Linz, Kepler University Hospital, Department of Pulmonology, Altenberger Strasse, 69, 4040 Linz and Krankenhausstrasse 9, 4020 Linz, Austria, Email Andreas.Horner@kepleruniklinikum.atBackground: Symptoms of depression, pain and limitations in physical activity may affect quality of life in COPD patients independent from their respiratory burden. We aimed to analyze the associations of these factors in outpatients with COPD in Austria in a stable phase of disease.Methods: We conducted a national, cross-sectional study among patients with COPD. For depression, the Patient Health Questionnaire-9 (PHQ-9) and for respiratory symptoms the St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C) were used along with 10-point scales for physical activity and pain.Results: After exclusion of 211 patients due to non-obstructive spirometry or missing data, 630 patients (62.5% men; mean age 66.8 ± 8.6 (SD) years; mean FEV1%pred. 54.3 ± 16.5 (SD)) were analyzed. Of these, 47% reported one or more exacerbations in the previous year, 10.4% with hospitalization. A negative depression score was found in 54% and a score suggesting severe depression (PHQ-9 score ≥ 15) in 4.7%. In a multivariate linear regression model, self-reported pain, dyspnea, and number of exacerbations were predictors for higher PHQ-9-scores. A negative pain score was found in 43.8%, and a score suggesting severe pain in 2.9% (8– 10 points of 10-point scale). Patients reporting severe pain were more often female, had more exacerbations, and reported more respiratory and depressive symptoms, a lower quality of life, and less physical activity. About 46% of patients rated their physical activity as severely impaired. These patients were significantly older, had more exacerbations, concomitant heart disease, a higher pain and depression score, and a lower quality of life (SGRQ-C – total score and all subscores).Conclusions: In Austria, nearly half of stable COPD outpatients reported symptoms of depression, which were associated with lower levels of self-reported physical activity, more pain, and respiratory symptoms. The associations were particularly strong for depression with SGRQ-C.Keywords: chronic obstructive pulmonary disease, depression, PHQ-9, pain, quality of life, St. George’s Respiratory Questionnaire, physical activity

Matthias Helmut Urban,1 Philipp Eickhoff,2 Georg-Christian Funk,1 Otto Chris Burghuber,1 Michael Wolzt,3 Arschang Valipour1 1Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria; 2Department of Obstetrics and Gynecology, St. Josef Hospital, Vienna, Austria; 3Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. Methods: The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. Results: Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. Conclusion: B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels. Keywords: cardiovascular risk, chronic obstructive pulmonary disease, comorbidity, subclinical atherosclerosis, biomarker

Objective: While Stewart's acid-base approach is increasingly used in clinical practice, it has also led to new controversies. Acid-base disorders can be seen from different viewpoints: on the diagnostic/clinical, quantitative/mathematical, or the mechanistic level. In recent years, confusion in the interpretation and terminology of Stewart's approach has arisen from mixing these different levels. This will be demonstrated on the basis of a detailed analysis of the mechanism of "dilutional acidosis." In the classical dilution concept, metabolic acidosis after resuscitation with large volumes is attributed to the dilution of serum bicarbonate. However, Stewart's approach rejects this explanation and offers an alternative one that is based on a decrease in a "strong ion difference." This mechanistic explanation is questionable for principal chemical reasons. The objective of this study is to clarify the chemical mechanism of dilutional acidosis.Methods: Experimental data and simulations of various dilution experiments, as well as theoretical and chemical considerations were used.Results: 1. The key to understanding the mechanism of dilutional acidosis lies in the open CO2/HCO3 (-)-buffer system where the buffer base (HCO3(-)) is diluted whereas the buffer acid is not diluted (constant pCO2). 2. The categorization in independent and dependent variables depends on the system regarded. 3. Neither the principle of electroneutrality, nor a change in [SID], nor increased H2O dissociation plays a mechanistic role.Conclusion: Stewart's approach is valid at the mathematical level but does not provide any mechanistic insights. However, the quantification and categorization of acid-base disorders, using Stewart approach, may be helpful in clinical practice.Electronic Supplementary Material: The online version of this article (doi:10.1007/s00134-009-1528-y) contains supplementary material, which is available to authorized users. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of metabolic acidosis is high in patients with chronic kidney disease (CKD). For the diagnosis, a blood gas analysis is necessary, but not always available. The aim of the study was to evaluate the base excess (BE) of the sodium-chloride difference (BE Na-Cl  = Na + -Cl - -34 mmol/l) as a screening parameter for hyperchloremic metabolic acidosis., Methods and Statistical Analysis: We retrospectively performed acid-base analyses of 168 non-dialysed patients with CKD according to the physiologic and to the Stewart's approach. We performed linear regression analysis, Bland-Altman plot and receiver operating characteristics (ROC) analysis of BE Na-Cl  and BE to evaluate the accuracy of BE Na-Cl  predicting the BE. We further investigated possible confounding factors., Results: The corrected R 2  for the correlation of BE Na-Cl  and BE was 0.60 (p < 0.001). The Bland-Altman plot showed a good overall agreement. The bias was negligible, but the 95%-limits of agreement showed a wide interval (10.4 mmol/l). For BE ≤ 2 mmol/l, the ROC analysis yielded an AUC of 0.89 and moderate sensitivity (0.75) and specificity (0.86) for the optimal BE Na-Cl  threshold (≤ 2 mmol/l). Subgroup analysis showed similar results. The main factor for the imprecision of BE Na-Cl  predicting the BE across all stages of CKD is the variability of the serum anion gap (SAG)., Conclusions: The BE Na-Cl  is not an adequate parameter for screening of hyperchloremic acidosis because of the high variability of the SAG. Only, if the BE Na-Cl  is ≤ 5 mmol/l, a hyperchloremic acidosis should be suspected. Therefore, a complete blood gas analysis is necessary for the correct diagnosis of acid-base disorders in patients with chronic kidney disease., Competing Interests: Declarations Conflicts of interest The authors declare no competing interests. Ethical approval The study was approved by the Ethics Committee of the medical faculty of the Johannes Kepler University Linz, Austria (1267/2020). Principles of ethical and professional conduct have been followed., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The gold standard for ruling out distant metastases as part of primary staging in lung cancer is whole-body 18 F-FDG-PET/CT, but this method is resource-intensive. Recent evidence suggests that examining only the thorax and upper abdomen may be sufficient 1 2 3. If a limited 18 F-FDG-PET/CT approach proves effective for proper staging, it could lead to quicker examinations and reduced radiation exposure. This study aimed to determine whether limited 18 F-FDG-PET/CT is adequate for the primary staging of lung cancer.In this study, a retrospective analysis of 161 patients (87 men, 74 women; age range 31-88 y) with recent or suspected lung cancer who had undergone a whole-body 18 F-FDG-PET/CT examination for primary staging at our clinic between 2018 and 2022 was conducted. None of these patients showed evidence of extrathoracic metastases before the 18 F-FDG-PET/CT examination. The images were divided into three regions: "head-neck" (HN), "thorax-upper abdomen" (TUA), and "lower abdomen-hip" (LAH). TNM staging based on the HN plus TUA region was compared with TNM staging based on the whole body.Among the 161 subjects, 7 (4%) showed malignancy-suspect lesions in HN, 110 (68%) in TUA and 7 (4%) had suspected distant metastases in LAH. The TNM staging based on HN plus TUA corresponded to TNM staging based on the whole body in 161 (100%) examinations. This finding aligns with similar results in previous literature. 18 F-FDG-PET/CT limited to HN and TUA yielded accurate staging in all cases. Adopting this method could facilitate the examination and correct staging of more individuals, reducing exam waiting times and physician reporting time and minimising radiation exposure., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

While glucocorticoids remain the standard first-line treatment for chronic idiopathic eosinophilic pneumonia (CIEP), the long-term use is marred by significant side effects. This case study explores the effectiveness of mepolizumab, an anti-interleukin‑5 (IL-5) monoclonal antibody, as a novel corticosteroid-free alternative in treating CIEP. A 50-year-old woman presented with a 3-week history of progressive shortness of breath, dry cough and night sweats. The blood tests showed eosinophilia, and chest radiography identified lung consolidations. The CIEP was confirmed, ruling out other conditions through a detailed clinical and bronchoscopic work-up. The patient declined to be treated with systemic glucocorticoids. Treatment with mepolizumab was remarkable for effectively resolving symptoms and improving radiological findings without any prior or concurrent glucocorticoid therapy. Notably, the patient remained relapse-free over a 2-year follow-up, underscoring mepolizumab's efficacy as a corticosteroid-free treatment for CIEP. This case study calls for further research into anti-IL‑5 treatment of rare respiratory conditions., (© 2024. The Author(s).)

Several trials have shown that low-dose computed tomography-based lung cancer screening (LCS) allows a substantial reduction in lung cancer-related mortality, carrying the potential for other clinical benefits. There are, however, some uncertainties to be clarified and several aspects to be implemented to optimize advantages and minimize the potential harms of LCS. This review summarizes current evidence on LCS, discussing some of the well-established and potential benefits, including lung cancer (LC)-related mortality reduction and opportunity for smoking cessation interventions, as well as the disadvantages of LCS, such as overdiagnosis and overtreatment. CLINICAL RELEVANCE STATEMENT: Different perspectives are provided on LCS based on the updated literature. KEY POINTS: Lung cancer is a leading cancer-related cause of death and screening should reduce associated mortality. This review summarizes current evidence related to LCS. Several aspects need to be implemented to optimize benefits and minimize potential drawbacks of LCS., (© 2024. The Author(s).)

Background: Lung cancer is a major health burden in Austria; however, limited real-world data exist on the diagnostic and treatment reality of lung cancer patients in Austria. The collection of high-quality data in a clinical setting is needed to gain insights into the real-world diagnostic and therapeutic management of lung cancer patients., Methods: The Karl Landsteiner Institute for Lung Research and Pulmonary Oncology implemented the Landsteiner lung cancer research platform (LALUCA), recruiting unselected lung cancer patients from two high volume centers in Vienna. This article describes the objectives, design, methodology of the registry and the process of implementation., Results: A multidisciplinary team of lung cancer specialists created a custom designed variable catalogue for the LALUCA platform consisting of 17 categories with 180 variables. Detailed information on clinical characteristics, diagnostic interventions, molecular pathology as well as curative and palliative treatment modalities are collected. During an implementation phase in 2020, the platform was optimized using the data of 50 patients. Since then a total of 1200 patients have been enrolled. Recruitment for the registry is ongoing with a recruitment rate of approximately 400 patients per year., Conclusion: The LALUCA registry is a web-based platform for the collection of real-world clinical data of lung cancer patients. Combining a large number of patients with a focus on gathering comprehensive data on diagnosis and treatment, the LALUCA registry provides a tool for investigation, evaluation, and improvement of the clinical management, survival and quality of care of Austrian lung cancer patients., (© 2024. The Author(s).)

Background: Adjustments to COPD maintenance treatment are based on different guidelines. In Austria, there is a lack of real-world data on treatment adjustments of COPD outpatients and their underlying rationale. The STEP study characterised change patterns of pharmacological maintenance therapy in COPD outpatients in predefined categories of step-up, step-down and switch, the underlying reasons, and predictors in clinical routine in Austria., Methods: STEP was a single-visit non-interventional study in Austria. 77 pulmonologists based in outpatient clinics documented previous and adapted COPD therapy, reason for change, patient characteristics, COPD phenotype, and lung function. Patients' COPD symptom burden was assessed by using the COPD Assessment Test (CAT). Predictors for therapy changes were identified., Results: 1137 patients were studied (mean±sd age 67±10 years; 56.9% male; mean forced expiratory volume in 1 s 56.3% predicted; Global Initiative for Chronic Obstructive Lung Disease B and E stages 66% and 19%, respectively; mean CAT score 17.5). Therapy step-up was observed in 59.3%, treatment switch in 21.7% and step-down in 19.0% of patients. Triple therapy comprised the biggest proportion of inhalation treatment (53.3%). Physicians reported lung function, symptom burden and exacerbations as the main reasons for step-up or step-down, whereas switches within the same treatment class were predominantly caused by device issues. Predictors for step-up were comorbid asthma and exacerbations among others., Conclusions: STEP was the first study to investigate COPD therapy changes in clinical routine in Austria. The most frequent treatment adjustment was step-up, followed by treatment switch and step-down. Symptom burden, stable or improved lung function and inhalation device handling were the most frequently given reasons for adjustments., Competing Interests: Conflict of interest: F. Vafai-Tabrizi reports support for the present manuscript from A. Menarini Pharma GmbH; consulting fees from A. Menarini Pharma GmbH, outside the submitted work; payment for lectures from Chiesi Pharma, AstraZeneca and Boehringer Ingelheim, outside the submitted work; and participation on a data safety monitoring board or advisory board for A. Menarini Pharma GmbH and Boehringer Ingelheim, outside the submitted work. U. Schwab reports support for the present manuscript from A. Menarini Pharma GmbH and is an employee of the medical department of A. Menarini Pharma GmbH. S. Brecht reports support for the present manuscript from A. Menarini Pharma GmbH and is an employee of the medical department of A. Menarini Pharma GmbH. G-C. Funk reports support for the present manuscript from A. Menarini Pharma GmbH; consulting fees from A. Menarini Pharma GmbH, Chiesi, AstraZeneca, Boehringer Ingelheim, CSL Behring and Novartis, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Menarini, Chiesi, AstraZeneca, Boehringer Ingelheim, CSL Behring and Novartis, outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work; and participation on a data safety monitoring or advisory board for A. Menarini Pharma GmbH, outside the submitted work., (Copyright ©The authors 2024.)

Rationale: Intravenous plasma-purified alpha-1 antitrypsin (IV-AAT) has been used as therapy for alpha-1 antitrypsin deficiency (AATD) since 1987. Previous trials (RAPID and RAPID-OLE) demonstrated efficacy in preserving computed tomography of lung density but no effect on FEV 1 . This observational study evaluated 615 people with severe AATD from three countries with socialized health care (Ireland, Switzerland, and Austria), where access to standard medical care was equal but access to IV-AAT was not. Objectives: To assess the real-world longitudinal effects of IV-AAT. Methods: Pulmonary function and mortality data were utilized to perform longitudinal analyses on registry participants with severe AATD. Measurements and Main Results: IV-AAT confers a survival benefit in severe AATD ( P  < 0.001). We uncovered two distinct AATD phenotypes based on an initial respiratory diagnosis: lung index and non-lung index. Lung indexes demonstrated a more rapid FEV 1 decline between the ages of 20 and 50 and subsequently entered a plateau phase of minimal decline from 50 onward. Consequentially, IV-AAT had no effect on FEV 1 decline, except in patients with a Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 lung index. Conclusions: This real-world study demonstrates a survival advantage from IV-AAT. This improved survival is largely decoupled from FEV 1 decline. The observation that patients with severe AATD fall into two major phenotypes has implications for clinical trial design where FEV 1 is a primary endpoint. Recruits into trials are typically older lung indexes entering the plateau phase and, therefore, unlikely to show spirometric benefits. IV-AAT attenuates spirometric decline in lung indexes in GOLD stage 2, a spirometric group commonly outside current IV-AAT commencement recommendations.

Background: Hyponatremia has prognostic implications in patients with cirrhosis, and thus, has been incorporated in the 2016 MELD-UNOS update. Changes in serum chloride are commonly perceived as 'just' parallel to changes in serum sodium. However, these are less well studied in the context of cirrhosis., Aims: To investigate whether serum chloride independently predicts outcomes in patients with advanced chronic liver disease (ACLD) and stable clinical course or with critical illness., Methods: 891 patients with ACLD (defined by hepatic venous pressure gradient [HVPG] ≥6 mm Hg) were followed after HVPG measurement between 2003 and 2020 (ACLD cohort). 181 critically ill patients with cirrhosis admitted to the ICU between 2004 and 2007 were recruited for the ICU cohort. Hypo-/hypernatremia (normal: 136-145 mmol/L) and hypo-/hyperchloremia (normal: 98-107 mmol/L) at baseline were assessed., Results: ACLD cohort: 68% of male patients with a median MELD (adjusted for Na) of 11 (9-17) were included (Child-Pugh-stages-A/B/C: 46%/38%/16%) and followed for a median of 60 months. Lower serum chloride (adjusted average HR per mmol/L: 0.965 [95% confidence interval (95% CI): 0.945-0.986], p = 0.001) showed a significant association with hepatic decompensation/liver-related mortality on multivariable Cox regression analysis adjusted for age, HVPG, albumin and MELD. In line, hypochloremia was significantly associated with hepatic decompensation/liver-related mortality (adjusted average HR: 1.656 [95% CI:1.267-2.163], p < 0.001). ICU cohort: 70% of patients were male, median MELD was 31(22-39) at ICU admission (92% with Child-Pugh-stage-C). After adjusting for hypo-/hypernatremia, MELD, and blood pH, hypochloremia remained independently associated with ICU-mortality (aOR Cl: 3.200 [95%CI: 1.209-8.829], p = 0.021)., Conclusion: Hypochloremia is associated with increased mortality in clinically stable and critically ill patients with cirrhosis independently of MELD including serum sodium., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Pleural biopsy findings offer greater diagnostic sensitivity in malignant pleural effusions compared with pleural fluid. The adequacy of pleural biopsy techniques in achieving molecular marker status has not been studied, and such information (termed "actionable" histology) is critical in providing a rational, efficient, and evidence-based approach to diagnostic investigation., Research Question: What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions?, Study Design and Methods: This study analyzed anonymized data on 183 patients from four sites across three countries in whom pleural biopsy results had confirmed a malignant diagnosis and molecular profiling was relevant for the diagnosed cancer type. The primary outcome measure was adequacy of pleural biopsy for achieving molecular marker status. Secondary outcomes included clinical factors predictive of achieving a molecular diagnosis., Results: The median age of patients was 71 years (interquartile range, 63-78 years), with 92 of 183 (50%) male. Of the 183 procedures, 105 (57%) were local anesthetic thoracoscopies (LAT), 12 (7%) were CT scan guided, and 66 (36%) were ultrasound guided. Successful molecular marker analysis was associated with mode of biopsy, with LAT having the highest yield and ultrasound-guided biopsy the lowest (LAT vs CT scan guided vs ultrasound guided: LAT yield, 95%; CT scan guided, 86%; and ultrasound guided, 77% [P = .004]). Biopsy technique and size of biopsy sample were independently associated with successful molecular marker analysis. LAT had an adjusted OR for successful diagnosis of 30.16 (95% CI, 3.15-288.56; P = .003) and biopsy sample size an OR of 1.18 (95% CI, 1.02-1.37) per millimeter increase in tissue sample size (P < .03)., Interpretation: Although previous studies have shown comparable overall diagnostic yields, in the modern era of targeted therapies, this study found that LAT offers far superior results to image-guided techniques at achieving molecular profiling and remains the optimal diagnostic tool., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Lung ultrasound has the potential to enable standardized follow-up without radiation exposure and with lower associated costs in comparison to CT scans. It is a valuable tool to follow up on patients after a COVID-19 infection and evaluate if there is pulmonary fibrosis developing. Echocardiography, including strain imaging, is a proven tool to assess various causes of dyspnea and adds valuable information in the context of long COVID care. Including two-dimensional (2D) strain imaging, a better comprehension of myocardial damage in post-COVID syndrome can be made. Especially 2D strain imaging (left and the right ventricular strain) can provide information about prognosis., (© 2022 American Institute of Ultrasound in Medicine.)

Background: Alpha-1-antitrypsin (AAT) deficiency (AATD) is a genetic disorder that can manifest as lung disease. A delay between onset of symptoms and diagnosis of AATD is common and associated with worse clinical status and more advanced disease stage but the influence on survival is unclear., Objective: We aimed to investigate the impact of diagnostic delay on overall survival (OS) and transplant-free survival (TS) in AATD patients., Methods: We analysed 268 AATD patients from the prospective multi-centre Austrian Alpha-1 Lung (AAL) Registry, employing descriptive statistics, Chi-square-test as well as univariable (Kaplan-Meier plots, log-rank test) and multivariable survival analysis (Cox regression)., Results: The predominant phenotype was Pi*ZZ (82.1%). At diagnosis, 90.2% had an AAT level below 0.6 g/L. At inclusion, 28.2% had never smoked, 68.0% had quit smoking and 3.8% continued to smoke. Lung disease was diagnosed in 98.5%, thereof most patients were diagnosed with emphysema (63.8%) and/or chronic obstructive pulmonary disease (44.0%). Median diagnostic delay was 5.3 years (inter-quartile range [IQR] 2.2-11.5 years). In multivariable analysis (n = 229), a longer diagnostic delay was significantly associated with worse OS (hazard ratio [HR] 1.61; 95% CI 1.09-2.38; p = 0.016) and TS (HR 1.43; 95% CI 1.08-1.89; p = 0.011), independent from age, smoking status, body mass index (BMI), forced expiratory volume in one second (FEV 1 ) and long-term oxygen treatment. Furthermore, BMI, age and active smoking were significantly associated with worse OS as well as BMI, active smoking and FEV 1 were with worse TS., Conclusions: A delayed diagnosis was associated with significantly worse OS and TS. Screening should be improved and efforts to ensure early AATD diagnosis should be intensified., (© 2023. The Author(s).)

Pulmonary embolism is one of the leading causes of cardiovascular death in Europe. Rapid diagnosis and treatment initiation are essential, especially in hemodynamically unstable patients. For normotensive patients, the diagnostic workflow is based on the clinical probability of pulmonary embolism. Due to numerous differential diagnoses and a highly variable clinical presentation, diagnosis of acute pulmonary embolism still remains a clinical challenge. Computed tomography angiography is the common gold standard to confirm pulmonary embolism and bedside echocardiography adds a major impact in clinical decision making. The European Society of Cardiology guidelines serve as a framework for a standardized diagnostic approach and risk prediction. Based on vital signs, clinical scores, biomarkers and imaging results, four risk categories can be defined and treatment is accordingly. To optimize the individual management of critical patients, multidisciplinary pulmonary embolism response teams are increasingly designated in specialized centers. This article provides an overview of the current risk-adapted management of patients with acute pulmonary embolism., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Objective: Chronic obstructive pulmonary disease (COPD) is associated with reduced exercise capacity. In COPD iron deficiency is found in up to 50% of patients and may impair exercise capacity, the potential therapeutic effect is yet unknown. We aimed to estimate the beneficial effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD., Methods: In this non-randomized, interrupted time series pilot trial we enrolled outpatients with stable COPD (GOLD II and III) and nonanemic iron deficiency (i.e., ferritin level < 100 μg/l or ferritin level 100-300 μg/l if transferrin saturation < 20%). Patients with cardiovascular-or inflammatory diseases were excluded. Participants performed 6‑minute walking test (6-MWT) and cardiopulmonary exercise testing (CPET) and completed the St. George's Respiratory Questionnaire (SGRQ)., Results: From 35 screened patients, 11 (72% male, 63 ± 8 years, FEV1%predicted 44 ± 14) were included. Mean ferritin and hemoglobin were 70 ± 41 µg/l and 13.8 ± 1.7 g/dl, respectively. Four weeks after iron administration the 6‑MWT distance increased by 34.7 ± 34.4 m (95% CI, 10.0-59.3); p = 0.011. The VO2max increased by 1.87 ± 1.2 ml/kg/min (95% CI, 0.76-3); p = 0.006. Mean score of SGRQ was reduced by 7.56 ± 6.12 units (95% CI, 3 to 11); p = 0.004. The insignificant alteration in hemoglobin did not correlate with increase in exercise capacity., Conclusion: Administration of intravenous iron was associated with improved exercise capacity and quality of life in stable COPD patients independent of hemoglobin. Our data provide a basis to calculate a statistically sufficient sample size for a randomized controlled follow-up study., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Electrolyte disorders are common in the emergency department. Hyponatremia is known to be associated with adverse outcome in community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD). No studies investigating the prevalence and influence of hypernatremia or potassium disorders in patients with AECOPD exist., Methods: In this retrospective cohort analysis, the prevalence of sodium and potassium disorders was investigated in patients with AECOPD presenting to an emergency department (ED) between January 1 st 2017 and December 31 st 2018 and compared to all ED patients with electrolyte measurements and patients presenting with CAP. Exclusion criteria were age younger than 18 years, written or verbal withdrawal of consent and outpatient treatment. Additionally, the influence of dysnatremias and dyskalemias on outcome measured by ICU admission, need for mechanical ventilation, length of hospital stay, 30-day re-admission, 180-day AECOPD recurrence and in-hospital mortality and their role as predictors of disease severity measured by Pneumonia Severity Index (PSI) were investigated in patients with AECOPD., Results: Nineteen point nine hundred forty-eight ED consultations with measurements of sodium and potassium were recognized between January 1 st 2017 and December 31 st 2018 of which 102 patients had AECOPD. Of these 23% had hyponatremia, 5% hypernatremia, 16% hypokalemia and 4% hyperkalemia on admission to the ED. Hypo- and hypernatremia were significantly more common in patients with AECOPD than in the overall ED population: 23 versus 11% (p = 0.001) for hypo- and 5% versus 0.6% (p < 0.001) for hypernatremia. In the logistic regression analysis, no association between the presence of either sodium or potassium disorders and adverse outcome were found., Conclusion: Dysnatremias and dyskalemias are common in patients with AECOPD with as many as 1 in 5 having hyponatremia and/or hypokalemia. Hypo- and hypernatremia were significantly more common in AECOPD than overall. No significant association was found for dysnatremias, dyskalemias and adverse outcomes in AECOPD., (© 2022. The Author(s).)

Background and Objectives: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for cardiovascular disease. This study aimed to investigate the relationship between pulmonary hyperinflation and baroreceptor reflex sensitivity (BRS), a surrogate for cardiovascular risk. Methods: 33 patients with COPD, free from clinical cardiovascular disease, and 12 healthy controls were studied. Participants underwent pulmonary function and non-invasive hemodynamic measurements. BRS was evaluated using the sequence method during resting conditions and mental arithmetic stress testing. Results: Patients with COPD had evidence of airflow obstruction [forced expiratory volume in 1 s predicted (FEV 1 %) 26.5 (23.3-29.1) vs. 91.5 (82.8-100.8); P < 0.001; geometric means (GM) with 95% confidence interval (CI)] and lung hyperinflation [residual volume/total lung capacity (RV/TLC) 67.7 (64.3-71.3) vs. 41.0 (38.8-44.3); P < 0.001; GM with 95% CI] compared to controls. Spontaneous mean BRS (BRSmean) was significantly lower in COPD, both during rest [5.6 (4.2-6.9) vs. 12.0 (9.1-17.6); P = 0.003; GM with 95% CI] and stress testing [4.4 (3.7-5.3) vs. 9.6 (7.7-12.2); P < 0.001; GM with 95% CI]. Stroke volume (SV) was significantly lower in the patient group [-21.0 ml (-29.4 to -12.6); P < 0.001; difference of the means with 95% CI]. RV/TLC was found to be a predictor of BRS and SV ( P < 0.05 for both), independent of resting heart rate. Conclusion: We herewith provide evidence of impaired BRS in patients with COPD. Hyperinflation may influence BRS through alteration of mechanosensitive vagal nerve activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mayr, Wieser, Funk, Asadi, Sperk, Urban and Valipour.)

Background: Diagnosis and treatment of influenza patients are often provided across several medical specialties. We compared patient outcomes at an infectious diseases (ID), a rheumatology (Rheu) and a pulmonology (Pul) department., Material and Methods: In this prospective observational multicenter study we included all influenza positive adults who were hospitalized and treated at flu isolation wards in three hospitals in Vienna during the season 2018/2019., Results: A total of 490 patients (49% female) with a median age of 73 years (interquartile range [IQR] 61-82) were included. No differences regarding age, sex and most underlying diseases were present at admission. Frequencies of the most common complications differed: acute kidney failure (ID 12.7%, Rheu 21.2%, Pulm 37.1%, p < 0.001), acute heart failure (ID 4.3%, Rheu 17.1%, Pulm 14.4%, p < 0.001) and respiratory insufficiency (ID 45.1%, Rheu 41.5%, Pulm 56.3%, p = 0.030). Oseltamivir prescription was lowest at the pulmonology flu ward (ID 79.6%, Rheu 90.5%, Pulm 61.7%, p < 0.001). In total 176 patients (35.9%) developed pneumonia. Antibiotic selection varied between the departments: amoxicillin/clavulanic acid (ID 28.9%, Rheu 63.8%, Pulm 5.9%, p < 0.001), cefuroxime (ID 28.9%, Rheu 1.3%, Pulm 0%, p < 0.001), 3rd generation cephalosporins (ID 4.4%, Rheu 5%, Pulm 72.5%, p < 0.001), doxycycline (ID 17.8%, Rheu 0%, Pulm 0%, p < 0.001). The median length of stay was significantly different between wards: ID 6 days (IQR 5-8), Rheu 6 days (IQR 5-7) and Pulm 7 days (IQR 5-9.5, p = 0.034). In-hospital mortality was 4.3% and did not differ between specialties., Conclusion: We detected differences in oseltamivir usage, length of in-hospital stay and antibiotic choices for pneumonia. Influenza-associated mortality was unaffected by specialty., (© 2021. Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS)., Methods: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO 2 , PaO 2 and NIV adherence (PROSPERO CRD42019132398)., Findings: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO 2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO 2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome., Interpretation: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks., Competing Interests: Competing interests: ML has no conflict of interest to declare related to the present work. He received speaker fees from Air Liquide Medical System, and Sefam, and non-financial support from Nomics outside the context of the submitted work. He received a salary from Air Liquide Medical System as a medical trainer. A Léotard has no conflict of interest to declare related to the present work. JC Borel is salaried by AGIR à dom, a home-care provider. JL Pépin and his department has received research support and personal fees from Philips Respironics, Sefam, Fisher and Paykel, and ResMed. JLP is supported by the French National Research Agency in the framework of the "Investissements d’avenir” program (ANR-15-IDEX-02) and the “e-health and integrated care and trajectories medicine and MIAI artificial intelligence” Chairs of excellence from the Grenoble Alpes University Foundation. This work has been partially supported by MIAI @ Grenoble Alpes (ANR-19-P3IA-0003). M Dreher has received speaking and advisor fees from companies in the field of mechanical ventilation; in addition, his study group received an open research grant from ResMed. JH Storre reports grants and personal fees for lectures from Heinen und Löwenstein and VitalAire, grants, personal fees for lectures and non-financial support for meeting attendance from Vivisol GmbH, grants from Weinmann Deutschland, personal fees for consultancy/advisory board work from Breas Medical AB regarding the submitted work; personal fees for consultancy and lectures, and non-financial support for meeting attendance from Boehringer Ingelheim Pharma, personal fees for consultancy and lectures from SenTec AG, Keller Medical GmbH, Linde Deutschland and Santis GmbH, outside the submitted work. M Patout reports personal fees from Resmed, Philips Respironics, grants and non-financial support from Fisher & Paykel, non-financial support and personal fees from Asten, research grants from B& D Electromedical and Fisher & Paykel, personal fees and non-financial support from Chiesi outside the submitted work. GC Funk received speaker fees from Draeger and Getinge. PJ Wijkstra reports grants and personal fees from Philips, grants and personal fees from RESMED, grants from Vital Air, grants from VIVISOL, grants from Goedegebuure, personal fees from Synapse, personal fees from Bresotec, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The potential mid-term and long-term consequences after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are as yet unknown. This is the first report of bronchoscopically verified organizing pneumonia as a complication of coronavirus disease 2019 (Covid19). It caused persisting dyspnea, impaired pulmonary function, and radiological abnormalities over 5 weeks after onset of symptoms. While organizing pneumonia frequently requires treatment with systemic corticosteroids, in this case it resolved spontaneously without treatment after 6 weeks. Healthcare professionals should consider organizing pneumonia in patients with persisting respiratory symptoms after Covid19., (© 2021. The Author(s).)

Background: Thiazide diuretics are a mainstay in the management of hypertension and often associated with dyselectrolytemias. We investigated the prevalence of and risk factors for hyponatremia and hypokalemia in thiazide users, substance-specific differences, and the association of thiazides with syncope and falls., Methods: In this cross-sectional analysis all patients admitted to an interdisciplinary emergency department in Switzerland between January 1, 2017, and December 31, 2018, with measurements of serum sodium and potassium were included. Data regarding serum electrolytes and creatinine were analyzed to classify for dysnatremias, dyskalemias, and acute kidney injury. Chart reviews were performed to screen for syncope or falls., Results: A total of 1604 patients (7.9%) took thiazides. Acute kidney injury was significantly more common in thiazide users (22.1 vs 7%, P < .0001). Hyponatremia (22.1 vs 9.8%, P < .0001) and hypokalemia (19 vs 11%, P < .0001) were more frequent with thiazides. Thiazide use together with higher age and female sex were independent predictors of hyponatremia and hypokalemia. A dose-dependent effect was found for electrolyte disorders, and there was a variance in risk between the investigated substances with chlorthalidone bearing the highest and hydrochlorothiazide the lowest risk. Patients taking thiazide diuretics had significantly more episodes of syncope and falls., Conclusions: Thiazide use is a clear risk factor for hyponatremia and hypokalemia. The effect appears to be dose-dependent and highly variable depending on the substance. Syncope and falls seem to be causally related to thiazide use. Especially in patients who are elderly, female, and prone to falls, the use of thiazide diuretics should be thoroughly questioned., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Elderly people, defined by age 65 years and older, made up 18.45% of the Swiss Population in 2018 and their number is projected to rise continuously. Data investigating specific characteristics of this patient subgroup, especially in the emergency setting, is scarce., Methods: Demographic data of admission records from all patients aged 65 years or older admitted to our emergency department (ED) between January 1st 2015 and December 31st 2018 were investigated. Retrospective chart reviews of patients admitted in 2018 were conducted. Comorbidity burden was assessed by Charlson Comorbidity Index. Risk factors for death, longer hospitalization and placement in a nursing facility were identified by multivariate regression., Results: The prevalence of elderly patients (≥65 years) admitted to the ED between 2015 and 2018 was rising from 33% in 2015 to 37.8% in 2018. In 2018 709 patients were 90 years and older (3.6%). Age above 90 years and high comorbidity burden were identified as independent risk factors for death. Polypharmacy, hyponatremia and high comorbidity burden were independent risk factors for longer hospitalizations. Advanced age and high comorbidity burden were independent risk factors for placement in a nursing facility., Conclusion: The number of elderly patients admitted to our ED is continuously rising. There was no difference in overall disease burden, number of medications and hospital length of stay between octogenarians and nonagenarians. We identified risk factors for mortality, long hospitalizations and need of placement in a nursing facility., Competing Interests: Declaration of competing interest None of the authors has a conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In recent years, large treatment studies have been published in the field of chronic obstructive pulmonary disease (COPD) and were supplemented by several post-hoc analyses in 2020. The new evidence was incorporated into the 2021 update of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report. This article describes the updated fundamentals of and recommendations for the treatment of COPD. Indications for inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and/or long-acting beta-mimetics (LABA) will be addressed. The treatment of COPD is contrasted with that of bronchial asthma. The impact of a concomitant asthma component on the treatment strategy for COPD is also discussed. In addition, the article focuses on triple therapy with LAMA, LABA, and ICS, for which the evidence and indications are described. Bronchodilation remains the foundation of COPD therapy. For patients with clustered exacerbations, triple therapy with LAMA + LABA + ICS confers a mortality benefit. Further analysis or studies are needed to clarify whether this effect is more pronounced for specific subgroups.

Objective: Diastolic dysfunction of the left ventricle is common in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been suggested as a key determinant of reduced diastolic function in COPD. We aimed to investigate the effects of induced dynamic hyperinflation on left ventricular diastolic function in healthy subjects to exclude other confounding mechanisms associated with COPD. Design: In this randomized controlled crossover trial (NCT03500822, https://www.clinicaltrials.gov/), we induced dynamic hyperinflation using the validated method of expiratory resistance breathing (ERB), which combines tachypnea with expiratory resistance, and compared the results to those of tachypnea alone. Healthy male subjects ( n = 14) were randomly assigned to the ERB or control group with subsequent crossover. Mild, moderate, and severe hyperinflation (i.e., ERB1, ERB2, ERB3) were confirmed by intrinsic positive end-expiratory pressure (PEEP i ) using an esophageal balloon catheter. The effects on diastolic function of the left ventricle were measured by transthoracic echocardiographic assessment of the heart rate-adjusted transmitral E/A-ratio and E/e'-ratio. Results: We randomly assigned seven participants to the ERB group and seven to the control group (age 26 [24-26] vs. 24 [24-34], p = 0.81). Severe hyperinflation decreased the E/A-ratio compared to the control condition (1.63 [1.49-1.77] vs. 1.85 [0.95-2.75], p = 0.039), and moderate and severe ERB significantly increased the septal E/e'-ratio. No changes in diastolic function were found during mild hyperinflation. PEEPi levels during ERB were inversely correlated with the E/A ratio (regression coefficient = -0.007, p = 0.001). Conclusions: Our data indicate dynamic hyperinflation as a determinant of left ventricular diastolic dysfunction in healthy subjects. Therapeutic reduction of hyperinflation might be a treatable trait to improve diastolic function in patients with COPD., Competing Interests: MU received grants from Nycomed Pharma as well as speaker fees and fees for advisory boards from Astra-Zeneca, Böhringer Ingelheim, Dräger, Sanitas, and Grünenthal. IS received personal fees for lectures from Astra-Zeneca, AOP, Orphan, Böhringer-Ingelheim and Chiesi. AM and EG-S have no conflicts of interest to declare. OB received unrestricted research grants from public governmental federal institutions and and from pharma industry (Menarini, Böhringer-Ingelheim, Chiesi, GSK, Pfizer, TEVA, Astra-Zeneca Air Liquide, MSD) as a member of the Ludwig Boltzmann Institute for Lung Health for the Austrian LEAD Study. He received personal fees for lecture and as member of advisory boards from Roche, Takeda, Nycomed and Astra-Zeneca. G-CF reports speaker fees and fees for advisory boards from Boehringer Ingelheim, Menarini, Janssen-Cilag, Novartis, Insmed Germany, Getinge, Draeger, CSL Behring, Orion Pharma, Astra Zeneca, Fresenius, Chiesi, Glaxo-Smith Kline, Roche; G-CF reports educational grants from Janssen-Cilag. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Urban, Mayr, Schmidt, Grasmuk-Siegl, Burghuber and Funk.)

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic marker in several inflammatory, respiratory and cardiovascular conditions, but has not been studied in COVID-19 yet., Methods: This prospective, observational study of patients with COVID-19 infection was conducted from 6 June to 26 November 2020 in different wards of a tertiary hospital. MR-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin I levels on admission were collected and tested for their association with disease severity and 28-day mortality., Results: A total of 213 eligible patients with COVID-19 were included in the final analyses of whom 13.2% (n = 28) died within 28 days. Median levels of MR-proANP at admission were significantly higher in nonsurvivors (307 pmol/L IQR, [161 - 532] vs 75 pmol/L [IQR, 43 - 153], P < .001) compared to survivors and increased with disease severity and level of hypoxaemia. The area under the ROC curve for MR-proANP predicting 28-day mortality was 0.832 (95% CI 0.753 - 0.912, P < .001). An optimal cut-off point of 160 pmol/L yielded a sensitivity of 82.1% and a specificity of 76.2%. MR-proANP was a significant predictor of 28-day mortality independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (HR 2.77, 95% CI 1.21 - 6.37; P = .016), while NT-proBNP failed to independently predict 28-day mortality and had a numerically lower AUC compared to MR-proANP., Conclusion: Higher levels of MR-proANP at admission are associated with disease severity of COVID-19 and act as a powerful and independent prognostic marker of 28-day mortality., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Coronavirus disease (COVID-19) was first described at the end of 2019 in China and has since spread across the globe. Red cell distribution width (RDW) is a potent prognostic marker in several medical conditions and has recently been suggested to be of prognostic value in COVID-19. Methods: This retrospective, observational study of consecutive patients with COVID-19 was conducted from March 12, 2020 to December 4, 2020 in the Wilhelminenhospital, Vienna, Austria. RDWlevels on admission were collected and tested for their predictive value of 28-day mortality. Results: A total of 423 eligible patients with COVID-19 were included in the final analyses and 15.4% died within 28 days ( n = 65). Median levels of RDWwere significantly higher in non-survivors compared to survivors [14.6% (IQR, 13.7-16.3) vs. 13.4% (IQR, 12.7- 14.4), P < 0.001]. Increased RDW was a significant predictor of 28-day mortality [crude odds ratio (OR) 1.717, 95% confidence interval (CI) 1.462-2.017; P = < 0.001], independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (adjusted OR of the final model 1.368, 95% CI 1.126-1.662; P = 0.002). This association remained consistent upon sub-group analysis. Our study data also demonstrate that RDW levels upon admission for COVID-19 were similar to previously recorded, non-COVID-19 associated RDW levels [14.2% (IQR, 13.3-15.7) vs. 14.0% [IQR, 13.2-15.1]; P = 0.187]. Conclusions: In this population, RDWwas a significant, independent prognostic marker of short-term mortality in patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kaufmann, Ahmed, Brunner, Jäger, Aicher, Equiluz-Bruck, Spiel, Funk, Gschwantler, Fasching and Huber.)

Background: Recently published studies indicated a high proportion of patients taking direct oral anticoagulants (DOACs) are off-label under- or overdosed. The present study aimed at investigating whether off-label dosages are corrected over time and whether off-label doses are associated with differences in bleeding rates, ischemic stroke, or venous thromboembolism., Methods: In this retrospective cohort study, patients presenting to our emergency department between January 1 and December 31, 2018, with therapeutic oral anticoagulation were included (ie, vitamin-K antagonists [VKAs], rivaroxaban, apixaban, edoxaban, and dabigatran) and follow-up for a maximum of 2 years until December 31, 2019, was made. Detailed chart reviews were performed for each case concerning characteristics, indication, bleeding complications, or changes in the used substance or dosage., Results: We reviewed 2588 consultations of 1228 patients receiving therapeutic oral anticoagulation. During the maximum follow-up period of 2 years vitamin K antagonists and rivaroxaban lost the largest proportions in favor of apixaban. The overall distribution of dosage correctness remained almost unimproved (correct dosing in 62.5%, underdosing in 23.6%, coverdosing in 13.9%).The corresponding outcomes did not differ with respect to bleeding events, ischemic stroke, or venous thromboembolism among various anticoagulants as well as between correct and off-label doses., Conclusions: A rising proportion of existing oral anticoagulation regimes was changed to apixaban, while the proportion of off-label dosages of all oral anticoagulants remained stable. No difference in bleeding rates, de novo strokes, or thromboembolisms was found between anticoagulants as well as between correct and off-label doses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Disorders of sodium and potassium are common and predictors of adverse outcome. Prevalence and impact on outcome of hypokalemia, hyperkalemia, hyponatremia and hypernatremia were investigated in emergency patients with community-acquired pneumonia (CAP)., Methods: Patients ≥18 years presenting to our emergency department between January 1st 2017 and December 31st 2018 with on-admission electrolyte measurements were included. Chart reviews were performed to identify patients with CAP., Results: 19.948 cases had measurements of sodium and potassium of which 469 had CAP (2.4%). Prevalence of hypo- and hypernatremia was significantly increased in patients with compared to those without CAP (hyponatremia: 28.8% vs. 10.5% respectively, p<0.0001; hypernatremia: 1.9% vs. 0.6% respectively, p=0.002). The prevalence of hypo- and hyperkalemia was significantly higher in patients with than without CAP (hypokalemia 15.6% vs. 11.4% respectively, p=0.004; hyperkalemia: 4.5% vs. 2.0% respectively, p=0.001). Hyponatremia was significantly associated with longer hospital stay in patients with CAP (regression coefficient 0.194, standard error 0.079, p=0.015). None of the investigated electrolyte disorders were predictive of 30-day re-admission and 180-day pneumonia recurrence rates. Use of loop diuretics was an independent predictor for 30-day re-admission (OR 2.351 (1.099-5.03). p=0.028). Pneumonia Severity Index (PSI) risk class was an independent predictor of 180-day pneumonia recurrence (OR 1.494 (1.022-2.184), p=0.038)., Conclusion: Dysnatremias and dyskalemias are common findings complicating CAP in emergency patients. Prevalence of hyponatremia was highest followed by hypokalemia. Hyponatremia was an independent predictor of prolonged length of hospital stay. Loop diuretic use was associated with 30-day readmission and PSI risk class with 180-day pneumonia recurrence., (Copyright © 2020. Published by Elsevier B.V.)

New Findings: What is the central question of this study? The study aimed to establish a novel model to study the chronic obstructive pulmonary disease (COPD)-related cardiopulmonary effects of dynamic hyperinflation in healthy subjects. What is the main finding and its importance? A model of expiratory resistance breathing (ERB) was established in which dynamic hyperinflation was induced in healthy subjects, expressed both by lung volumes and intrathoracic pressures. ERB outperformed existing methods and represents an efficacious model to study cardiopulmonary mechanics of dynamic hyperinflation without potentially confounding factors as present in COPD., Abstract: Dynamic hyperinflation (DH) determines symptoms and prognosis of chronic obstructive pulmonary disease (COPD). The induction of DH is used to study cardiopulmonary mechanics in healthy subjects without COPD-related confounders like inflammation, hypoxic vasoconstriction and rarefication of pulmonary vasculature. Metronome-paced tachypnoea (MPT) has proven effective in inducing DH in healthy subjects, but does not account for airflow limitation. We aimed to establish a novel model incorporating airflow limitation by combining tachypnoea with an expiratory airway stenosis. We investigated this expiratory resistance breathing (ERB) model in 14 healthy subjects using different stenosis diameters to assess a dose-response relationship. Via cross-over design, we compared ERB to MPT in a random sequence. DH was quantified by inspiratory capacity (IC, litres) and intrinsic positive end-expiratory pressure (PEEPi, cmH 2 O). ERB induced a stepwise decreasing IC (means (95% CI): tidal breathing: 3.66 (3.45-3.88), ERB 3 mm: 3.33 (1.75-4.91), 2 mm: 2.05 (0.76-3.34), 1.5 mm: 0.73 (0.12-1.58) litres) and increasing PEEPi (tidal breathing: 0.70 (0.50-0.80), ERB 3 mm: 11.1 (7.0-15.2), 2 mm: 22.3 (17.1-27.6), 1.5 mm: 33.4 (3.40-63) cmH 2 O). All three MPT patterns increased PEEPi, but to a far lesser extent than ERB. No adverse events during ERB were noted. In conclusion, ERB was proven to be a safe and efficacious model for the induction of DH and might be used for the investigation of cardiopulmonary interaction in healthy subjects., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: In this study we analyzed gender differences in the clinical presentation of patients with molecular confirmed influenza A. Additionally, we tried to identify predictors of influenza-associated mortality., Materials/methods: In this prospective observational multi-center-study we included all influenza-positive patients ≥ 18 years who were hospitalized and treated on flu-isolation-wards in three hospitals in Vienna during the 2018/19 influenza season. Diagnoses were made via Cobas ® Liat ® POCT., Results: 490 Patients (48.8% female) tested positive for influenza A. Female patients were older (median age 76 years vs. 70 years, p < 0.001). Male patients had a higher rate of chronic liver disease in history (8.8% vs. 2.9%, p = 0.006), myositis (11.7% vs. 3.1%, p < 0.001) and ICU admissions (9.6% vs. 4.6%, p = 0.03). The in-hospital mortality rate was 4.3% and increased to 9.5% during the 90-day follow-up period. Female patients > 75 years had a significantly higher in-hospital mortality rate than ≤ 75-year-old females (9.2% vs. 1.7%, p = 0.019). This effect was not observed in male patients (5.4% vs. 1.9%, p = ns). Age > 75 years (OR 5.49, 95% CI 1.10-27.43), acute heart failure (OR 3.56, 95% CI 1.03-12.05) and ICU admission (OR 6.1, 95% CI 0.98-37.91) were predictors for in-hospital mortality for female patients, while any malignancy (OR 9.4, 95% CI 1.90-46.54) and ICU admission (OR 7.05, 95% CI 1.44-34.55) were predictors in male patients., Conclusions: Gender is associated with differences in clinical presentation and complications of influenza A virus infection. Women with acute heart failure or aged > 75 years have an increased risk of influenza associated in-hospital mortality, while ICU admission and any malignancy are predictors for male patients. Mortality rates in patients > 75 years are 5-10 times higher compared to their non-hospitalized influenza-negative Austrian counterparts.

Background and Objective: Cardiovascular risk is substantially increased in patients with COPD and can be quantified via arterial stiffness. The PDE-IV inhibitor roflumilast revealed a potential reduction of COPD-related cardiovascular risk. We aimed to investigate the effects of roflumilast on arterial stiffness by quantification of pulse wave velocity (PWV) in stable COPD., Methods: In this randomized placebo-controlled trial, 80 COPD patients received roflumilast or placebo for 24 weeks. The primary outcome was the change in cf-PWV. Secondary outcomes comprised markers of vascular function (e.g. Aix and RHI), systemic inflammation (e.g. IL-6 and TNF-α) and clinical characteristics of COPD (e.g. CAT and 6MWT)., Results: A total of 33 and 34 patients completed the roflumilast and placebo arm, respectively (age, median (IQR): 64.5 (61-69.5) vs 64.5 (56-72) years; FEV 1 , median (IQR): 34.5 (25.5-48.6) vs 35.3 (27-46.8) % predicted; 6MWT, median (IQR): 428 (340-558) vs 456 (364-570) m). Change from baseline PWV did not show a significant difference between roflumilast and placebo (+5.0 (95% CI: -2.0 to +13.0) vs 0.0 (95% CI: -7.0 to +7.0)%, P = 0.268). Roflumilast did not improve markers of vascular function or systemic inflammation. We observed a significant improvement in change from baseline 6MWT with roflumilast versus placebo (+53.0 (95% CI: +19.1 to +86.9) vs -0.92 (95% CI: -35.1 to +33.3) m, P = 0.026)., Conclusion: Our study revealed no beneficial effects of roflumilast on arterial stiffness. Further studies are needed to test a potential improvement of exercise capacity with roflumilast in COPD., (© 2020 Asian Pacific Society of Respirology.)

Carcinoid tumours are rare neuroendocrine neoplasms that mostly occur in younger adults with low tendencies to metastasise. Based on their histological characteristics, they are divided into typical and atypical subtypes. The most common presenting symptoms are due to central airway obstruction. The first step in the diagnostic assessment should be a computed tomography (CT) scan, as it provides information both for local tumour extent and lymph node involvement. Bronchoscopy is the main tool for histological confirmation, evaluation of bronchial wall invasion and removal of endobronchial manifestation with subsequent resolution of atelectasis. Endobronchial ultrasound may be necessary to rule out lymph node metastasis. Somatostatin receptor scintigraphy in combination with CT can rule out further metastatic disease.Surgical resection using parenchyma-sparing techniques remains the gold standard for treatment. For selected patients, endobronchial therapy could be an alternative for minimal invasiveness. Long-term follow-up is suggested due to the high likelihood of recurrence.Here, we describe our clinical experience in a 35-year-old male patient who originally presented with haemoptysis and a central polypoid tumour in the left main bronchus revealed by a CT scan. The histological characteristics were indicative of a typical carcinoid. The patient was treated using an endobronchial approach only. No complications and no recurrences have been observed in a follow-up of 2 years., Competing Interests: Conflict of interest: A. Papaporfyriou reports grants from European Respiratory Society, during the conduct of the study. Conflict of interest: J. Domayer has nothing to disclose. Conflict of interest: M. Meilinger has nothing to disclose. Conflict of interest: I. Firlinger has nothing to disclose. Conflict of interest: G-C. Funk has nothing to disclose. Conflict of interest: U. Setinek has nothing to disclose. Conflict of interest: K. Kostikas has nothing to disclose. Conflict of interest: A. Valipour has nothing to disclose., (Copyright ©ERS 2021.)

Background: No data concerning the prevalence and risk factors of dyskalemia in acute kidney injury (AKI) exist. We investigated (a) prevalence rates, (b) risk factors and (c) outcome of hypo- and hyperkalemia in emergency patients., Methods: In this cross-sectional analysis, all patients admitted to the emergency department of a large public hospital in Switzerland between January 1st 2017 and December 31st 2018 with measurements of creatinine and potassium were included. Baseline characteristics, medication and laboratory data were extracted. Chart reviews were performed to identify patients with a diagnosis of chronic kidney disease (CKD) and to extract their baseline creatinine. For all other patients, the ADQI backformula was used in order to calculate baseline creatinine. AKI was graduated using creatinine criteria of the acute kidney injury network. Binary logistic regression analysis was used to identify risk factors for appearance of hyperkalemia and outcome., Results: AKI was found in 8% of patients. Hyperkalemia was present in 13% and hypokalemia in 11% of patients with AKI. AKI stage, potassium-sparing diuretics, ACE inhibitors and underlying CKD were the strongest risk factors for hyperkalemia. Hyperkalemia as well as profound hypokalemia were independently associated with prolonged length of stay and in-hospital mortality. The study is limited by its dependency on chart review data in order to identify patients with chronic kidney disease and by limitations of the ADQI backformula to calculate baseline creatinine., Conclusions: Dyskalemias are common in emergency patients with AKI and are independent risk factors for adverse outcomes. Potassium-sparing diuretics, ACE-inhibitors, AKIN stage and CKD are predictors of hyperkalemia in AKI., (© 2020 John Wiley & Sons Ltd.)

Purpose: We aimed to investigate the prevalence, risk factors and outcome of hypo- and hypernatremia in emergency patients with acute kidney injury (AKI)., Methods: In this cross-sectional analysis all emergency patients between January 1st 2017 and December 31st 2018 with measurements of creatinine and sodium were included. Baseline characteristics, medication and laboratory data were gathered. Chart reviews were performed to identify patients with a diagnosis of chronic kidney disease (CKD) and to extract baseline creatinine. For all other patients the ADQI backformula was used to calculate baseline creatinine. AKI was graduated using creatinine criteria of the acute kidney injury network. Binary logistic regression analysis was used to identify risk factors for appearance of dysnatremias and outcome., Results: AKI was found in 8% of patients. 392 patients (23.16%) had hyponatremia, 24 (1.4%) had hypernatremia. Use of potassium sparing diuretics, a medical cause for emergency referral, use of thiazide diuretics and AKI stage were the strongest risk factors for hyponatremia. Loop diuretics, a medical cause for emergency referral and AKI stage were risk factors for hypernatremia. In patients with all classes of hyponatremia, length of hospital stay was significantly longer compared to patients with a normal serum sodium. In the binary logistic regression analysis with death as outcome, hyponatremia as well as severe hypernatremia were independent risk factors for mortality., Conclusions: Dysnatremias are common in emergency patients with AKI. Diuretic medication is a major risk factor for hypo- and hypernatremia. Both hyponatremia and severe hypernatremia were independent risk factors for adverse outcome., Competing Interests: Declaration of competing interest None of the authors has a conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Acid base and electrolyte disorders are frequently reported in the early period after renal transplantation. No comprehensive data exist on the prevalence and patterns of, and contributing factors to, electrolyte disturbances in patients with stable long-term allograft function., Methods: We analysed 576 renal transplant recipients (serum creatinine level &lt;2.0 mg/dl) in a cross-sectional study to evaluate the prevalence of electrolyte disorders and the risk factors associated with their occurrence., Results: A total of 369 patients (64%) of all allograft recipients (n = 576) showed at least one electrolyte and acid base disorder. The most abundant disorder was hypomagnesaemia (25%, n = 143), followed by hyperkalaemia (12.8%, n = 74), hypercalcaemia (12%, n = 69), hypophosphataemia (11.6%, n = 67), metabolic acidosis (11.1%, n = 61) and hyponatraemia (9%, n = 52). All other electrolyte disorders were rare (&lt;6%). In most cases the electrolyte disorders could be classified as mild. Forty percent of the cases had a combined disorder, but without a preferential pattern of combinations. In a multivariate logistic regression analysis, the most important factors contributing significantly to the occurrence of electrolyte disorders were renal function and concomitant medications., Conclusion: Acid base and electrolyte disorders are frequently observed in stable renal allograft recipients, but are usually mild. A combination of two or more electrolyte abnormalities often occurs, although no predominant pattern of a unique combination of electrolyte disorder is recognizable. &nbsp.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Over the past few years, there has been cumulating interest in describing this heterogeneity and using this information to group patients into different COPD phenotypes. The term phenotype is defined as single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes. It describes also the physical appearance or biochemical characteristics which result from the genotype-environment interaction. Furthermore, it clearly identifies subgroups with a significant impact in the prognosis. Recently, approaches to COPD phenotyping have been significantly enhanced in tandem with developments in understanding the disease's various pathological, clinical and genetic features. This knowledge inspired the researchers to investigate more tailored therapeutic strategies that could not only give a more potent effect but also help to avoid the traditional therapy's undesirable side effects. Eventually, it could be said that the phenotypic approach to COPD in the last decade had a huge impact on daily practice and management delivered to COPD patients. In this review, we highlight the impact of pharmacological and non-pharmacological treatment options on COPD outcomes, using a personalized treatment strategy based on different phenotypes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-2219). The series “Lung Emphysema” was commissioned by the editorial office without any funding or sponsorship. Dr. GCF reports grants and personal fees from Boehringer Ingelheim, personal fees from Astra Zeneca, grants from Menarini, outside the submitted work. Dr. AV reports personal fees from Astra Zeneca, grants, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Chiesi, personal fees from Menarini, personal fees from Novartis, outside the submitted work. The authors have no other conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objectives: We aimed to clarify the prevalence, indications, analgesic comedications and complications of prescription opioid use in patients presenting to a large emergency department (ED)., Design: Retrospective chart review., Setting: Large, interdisciplinary ED of a public hospital., Participants: All patients aged ≥18 years presenting between 1 January 2017, and 31 December 2018, with documentation on medication were included., Interventions: None., Primary and Secondary Outcome Measures: Prevalence rates for prescription opioid use and its indication. Prevalence of analgesic comedications in prescription opioid users. Hospitalisation rate, 72 hours ED reconsultation rate, 30-day rehospitalisation rate, in-hospital mortality., Results: A total of 26 224 consultations were included in the analysis; 1906 (7.3%) patients had prescriptions for opioids on admission to the ED. The main indications for opioid prescriptions were musculoskeletal disease in 1145 (60.1%) patients, followed by neoplastic disease in 374 (19.6%) patients. One hundred fifty-four (8.2%) consultations were directly related to opioid intake, and 50.1% of patients on opioids also used other classes of analgesics. Patients on prescription opioids were older (76 vs 62 years, p<0.0001) and female individuals were over-represented (58 vs 48.9%, p<0.0001). Hospitalisation rate (78.3 vs 49%, p<0.0001), 72 hours ED reconsultation rate (0.8 vs 0.3%, p=0.004), 30-day rehospitalisation rate (6.2 vs 1.5%, p<0.0001) and in-hospital mortality (6.3 vs 1.6%, p<0.0001) were significantly higher in patients with opioid therapy than other patients. In 25 cases (1.3%), admission to the ED was due to opioid intoxication., Conclusions: Daily prescription opioid use is common in patients presenting to the ED. The use of prescription opioids is associated with adverse outcomes, whereas intoxication is a minor issue in the studied population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Empirically, a significant proportion of patients using direct oral anticoagulation (DOAC) take off-label reduced doses. We aimed to investigate the prevalence, indications, dosages, and bleeding complications of oral anticoagulants on admission to the emergency department., Methods: In this retrospective analysis, patients presenting to our emergency department between January 1 and December 31, 2018, with therapeutic oral anticoagulation were included (ie, vitamin-K antagonists, rivaroxaban, apixaban, edoxaban, and dabigatran). A detailed chart review was performed for each case concerning characteristics, indication, and bleeding complications., Results: A total of 19,662 consecutive cases in the emergency department were reported: 1721 (9%) had therapeutic oral anticoagulation. Vitamin-K antagonists (41%), rivaroxaban (36%), and apixaban (19%) were the most common. Stroke prophylaxis in patients with atrial fibrillation (63.2%) and venous thromboembolism (24.1%) were the most common indications. In 27 cases (1.6%), no indication could be identified; further, 32% of patients were classified to have either off-label doses of DOACs or an international normalized ratio (INR) out of range (in vitamin-K antagonists), whereas 20% were classified as off-label underdosed and 12% as overdosed. No difference in the likelihood of bleeding on admission could be found between the respective drugs. Only concomitant use of aspirin was significantly associated with presence and higher severity of bleeding., Conclusions: Vitamin-K antagonists are still the most widely used drug followed by rivaroxaban. A significant proportion of patients are being prescribed off label-doses. While no difference was found for the respective anticoagulants with respect to bleeding, concomitant aspirin use was a significant predictor for bleeding in our collective., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In moderate-to-severe chronic obstructive pulmonary disease (COPD) patients the 6-min walk test (6MWT) is often exhaustive and correlates with the incremental cycle cardiopulmonary exercise test (CPET)., Objectives: The aim of this study was to assess the agreement between oxygen uptake (VO2) measured during the 6MWT by portable equipment and incremental cycle exercise in COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-IV., Methods: A total of 30 patients with COPD GOLD I-IV (14 patients GOLD stage I and II and 16 patients GOLD stage III and IV) underwent a 6MWT and an incremental CPET. Breath-by-breath analysis for VO2, carbon dioxide output (VCO2), and minute ventilation (VE) were measured during each test. Blood gas analysis and lactate measurements were performed before, during, and after the test., Results: VO2 in COPD patients GOLD stage I and II was 16.2 ± 4.2 mL/kg/min measured by 6MWT and 20.5 ± 7.0 mL/kg/min measured by CPET as compared to GOLD stage III and IV (11.2 ± 3.7 mL/kg/min measured by 6MWT and 15.5 ± 4.3 mL/kg/min measured by CPET). No significant correlation in VO2 measurements could be found between both tests in COPD GOLD I and II (r = 0.17), whereas the VO2 significantly correlated in patients with COPD stage III and IV (r = 0.7)., Conclusions: A significant relationship between VO2 measured by 6MWT and CPET could only be found in patients with more severe COPD but not in milder stages. 6MWT and CPET provide different VO2 measurements in COPD patients. The two methods cannot be used interchangeably., (© 2020 S. Karger AG, Basel.)

Keeping blood pH levels stable within narrow limits is prerequisite for maintaining normal body function. Disruptions of this equilibrium can occur for a variety of reasons and may result in life-threatening conditions. Therefore, the identification and the interpretation of acid-base disorders are of great importance in emergency medicine. The same applies to intensive care as well as to almost all areas of internal medicine. In this article, we provide a practical overview of all relevant acid-base disorders that are due to both metabolic and respiratory disturbances. In addition, it shows how they can be diagnosed in everyday clinical practice by applying the simplified Stewart Approach.

Introduction: End-stage chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure are often treated by representatives from different medical specialties. This study investigates if the choice of treatment is influenced by the medical specialty., Methods: An online cross-sectional survey among four Austrian medical societies was performed, accompanied by a case vignette of a geriatric end-stage COPD patient with acute respiratory failure. Respondents had to choose between noninvasive ventilation (NIV), a conservative treatment attempt (without NIV) and a palliative approach. Ethical considerations and their impact on decision making were also assessed., Results: Responses of 162 physicians (67 from intensive care units (ICUs), 51 from pulmonology or internal departments and 44 from geriatric or palliative care) were included. The decision for NIV (instead of a conservative or palliative approach) was associated with working in an ICU (OR 14.9, 95% CI 1.87-118.8) and in a pulmonology or internal department (OR 9.4, 95% CI 1.14-78.42) compared with working in geriatric or palliative care (Model 1). The decision for palliative care was negatively associated with working in a pulmonology or internal department (OR 0.16, 95% CI 0.05-0.47) and (nonsignificantly) in an ICU (OR 0.41, 95% CI 0.15-1.12) (Model 2)., Conclusions: Department association was shown to be an independent predictor for treatment decisions in end-stage COPD with acute respiratory failure. Further research on these differences and influential factors is necessary., Competing Interests: Conflict of interest: M. Gäbler has nothing to disclose. Conflict of interest: G. Ohrenberger has nothing to disclose. Conflict of interest: G-C. Funk reports a speaker fee from AstraZeneca, service on an advisory board for GSK, a speaker fee from and service on an advisory board for Boehringer Ingelheim, and a speaker fee from Orion Pharma, outside the submitted work.

This paper was created by the Austrian Society of Pneumology (Working group Ventilation and Intensive Care) to summarize the specific characteristics of mechanical ventilation in patients presenting with chronic obstructive pulmonary disease (COPD). The main differences in pathophysiology and mechanical ventilation are shown, including acute respiratory failure and out-of-hospital mechanical ventilation.