Horst Olschewski

Medical University of Graz · Abteilung für Pulmonologie

Pulmonary hypertension (PH) is a frequent complication of chronic lung disease (CLD). However, PH is difficult to diagnose early since accompanying symptoms overlap and are similar to those of the underlying CLD. In most cases the PH is mild to moderate and therefore physical signs may be absent or subtle. This consensus paper provides insight into...

Background Exercise pulmonary hypertension (exercise PH) was defined by a mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope >3 mmHg·L ⁻¹ ·min ⁻¹ between rest and exercise in the 2022 ESC/ERS PH guidelines. However, large, multi-center studies on the prognostic relevance of exercise hemodynamics and its added value to resting hemodyn...

Pulmonary veno-occlusive disease has a significantly worse prognosis than idiopathic pulmonary arterial hypertension. According to a case series from France, the median survival time from diagnosis to death or lung transplantation was only 1 year, and in a more recent analysis, pulmonary arterial hypertension therapy had no significant effect on su...

Introduction . Pulmonary hypertension (PH) definition was recently changed and led to a new subset of PH patients with mildly impaired pulmonary hemodynamics, characterized by a mean pulmonary artery pressure of 21–24 mmHg and with a pulmonary vascular resistance >2Wood Units. We evaluated the association of PH-targeted therapy and outcome in mild...

Risk stratification has gained an increasing role in predicting outcomes and guiding the treatment of patients with pulmonary arterial hypertension (PAH). The most predictive prognostic factors are three noninvasive parameters (World Health Organization functional class, 6-min walk distance and natriuretic peptides) that are included in all current...

Purpose of review In this review, we provide an overview of the prognostic implications of exPH in patients with various common cardiac and pulmonary diseases. Recent findings Exercise pulmonary hypertension (exPH) has been recently re-introduced in the current European Society of Cardiology/European Respiratory Society pulmonary hypertension guid...

Purpose The aim of this study was to evaluate the association between computed tomography (CT) quantitative pulmonary vessel morphology and lung function, disease severity, and mortality risk in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods Participants of the prospective nationwide COSYCONET cohort study with pa...

Pulmonary fibrosis (PF) can be a fatal disease characterized by progressive lung scarring. It is still poorly understood how the pulmonary endothelium is involved in the disease pathogenesis. Differences of the pulmonary vasculature between patients and donors were analyzed using transmission electron microscopy, immunohistochemistry, and single-ce...

Rationale Severe pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is currently defined by an elevated mean pulmonary arterial pressure and strongly elevated pulmonary vascular resistance >5 wood units. Clinically, these patients show a male predominance, and usually present with very severe dyspnea, severe hypoxemia, stro...

Background and purpose Pulmonary arterial hypertension (PAH) is a progressive disease in which chronic membrane potential (Em) depolarisation of the pulmonary arterial smooth muscle cells (PASMCs) causes calcium overload, a key pathological alteration. Under resting conditions, the negative Em is mainly set by two pore domain potassium (K2P) channe...

BACKGROUND Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the im...

Background There is an unmet need for easily available sensitive markers of structural lung disease. Assessment of lung diffusion capacity with foreign gases is currently state-of-the-art, however, results are unspecific and the methods are technically demanding. We developed a fully-automatic algorithm to analyze high-fidelity expiratory CO2 flows...

Background 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 pati...

Zusammenfassung In der Neufassung der ESC/ERS-Leitlinien 2022 zur pulmonalen Hypertonie (PH) kam es zu wesentlichen Änderungen in der hämodynamischen Definition sowie zu einer weiteren Verfeinerung in der Klassifikation des Lungenhochdrucks. Als bedeutende Neuerung gilt die Einführung eines neuen Grenzwerts des mittleren pulmonalarteriellen Druckes...

Although progress has been made in the therapy of pulmonary arterial hypertension (PAH), diagnosis is often late and therapy aims at vasoconstriction instead of the underlying mechanisms of pulmonary arterial (PA) remodeling. There is a need for biomarkers that are functional, diagnostic and prognostic and provide new targets for treatment. We use...

Deposition of basement membrane components, such as collagen IVα5, is associated with altered endothelial cell function in pulmonary hypertension. Collagen IVα5 harbors a functionally active fragment within its C-terminal non-collageneous (NC1) domain, called pentastatin, whose role in pulmonary endothelial cell behavior remains unknown. Here, we d...

Background: While computed tomography pulmonary angiography (CTPA) is an integral part of the work-up in patients with suspected pulmonary hypertension (PH), there is no established CTPA-derived prognostic marker. We aimed to assess whether quantitative readouts of lung vessel morphology correlate with established prognostic indicators in PH. Met...

Purpose: Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. Genetic testing is currently recommended for adults diagnosed with heritable, idiopathic, anorexigen-, hereditary hemorrhagic telangiectasia-, and congenital heart disease-associated PAH, PAH with overt featu...

Background Immune cell recruitment, endothelial cell barrier disruption, and platelet activation are hallmarks of lung injuries caused by COVID-19 or other insults which can result in acute respiratory distress syndrome (ARDS). Basement membrane (BM) disruption is commonly observed in ARDS, however, the role of newly generated bioactive BM fragment...

Pulmonary hypertension (PH) is a severe hemodynamic, progressive condition associated with high morbidity and mortality where early and less invasive diagnostics could crucially improve management. There is a need for biomarkers in PH that are functional, diagnostic, and prognostic. We used a broad metabolomics approach with machine learning analys...

b>Hintergrund: Anhaltende Symptome nach akuter Coronavirus-Krankheit-2019 (COVID-19) sind häufig und es besteht kein signifikanter Zusammenhang mit der Schwere der akuten Erkrankung. Bei Long COVID (anhaltende Symptome > 4 Wochen nach akuter COVID-19) treten häufig respiratorische Symptome auf, aber Lungenfunktionstests zeigen nur leichte Veränderu...

In the recently published European Society of Cardiology/European Respiratory Society guidelines on the diagnosis and treatment of pulmonary hypertension (PH) the haemodynamic definitions of PH were updated and a new definition for exercise PH was introduced. Accordingly, exercise PH is characterised by a mean pulmonary arterial pressure/cardiac ou...

COPD is a heterogeneous disease with multiple clinical phenotypes. COPD endotypes can be determined by different expressions of hypoxia-inducible factors (HIFs), which, in combination with individual susceptibility and environmental factors, may cause predominant airway or vascular changes in the lung. The pulmonary vascular phenotype is relatively...

Background: NT-proBNP and GDF-15 are established blood-derived biomarkers for risk assessment in pulmonary hypertension (PH), despite limited sensitivity and specificity. Apelin has a crucial function in endothelial homeostasis, thus it might represent a new biomarker for PH. However, there are numerous circulating apelin isoforms, and their potent...

While Convolutional neural networks (CNN) have been the backbone of medical image analysis for years, their limited long-range interaction restrains their ability to encode long distance anatomical relationships. On the other hand, the current approach to capture long distance relationships, Transformers, is constrained by their quadratic scaling a...

Background Pulmonary hypertension (PH) is a frequent complication in COPD and it is associated with decreased exercise capacity and poor prognosis. We hypothesized that even in COPD patients without significant PH at rest, abnormal pulmonary hemodynamics during exercise affect exercise capacity. Methods Consecutive COPD patients with clinically in...

Background: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the s...

Background Pulmonary hypertension (PH) is a frequent complication in COPD and it is associated with decreased exercise capacity and poor prognosis. We hypothesized that even in COPD patients without significant PH at rest, abnormal pulmonary hemodynamics during exercise affect exercise capacity. Methods Consecutive COPD patients with clinically ind...

Since their introduction by Sabour et al., capsule networks have been extended to 2D semantic segmentation with the introduction of convolutional capsules. While extended further to 3D semantic segmentation when mixed with Convolutional Neural Networks (CNNs), no capsule-only network (to the best of our knowledge) has been able to reach CNNs’ accur...

A central feature of progressive vascular remodeling is altered smooth muscle cell (SMC) homeostasis; however, the understanding of how different cell populations contribute to this process is limited. Here, we utilized single cell RNA sequencing to provide insight into cellular composition changes within isolated pulmonary arteries (PA) from pulmo...

Background & aims Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown i...

https://doi.org/10.1093/eurheartj/ehac237

Pulmonary hypertension (PH) has been linked to worse outcome in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is t...

Background Mean pulmonary artery wedge pressure (PAWP) represents a right heart catheter (RHC) surrogate measure for mean left atrial (LA) pressure and is crucial for the clinical classification of pulmonary hypertension (PH). Hypothesizing that PAWP is related to acceleration of blood throughout the LA, we investigated whether an adequately introd...

Fine control over chloride homeostasis in the lung is required to maintain membrane excitability, transepithelial transport as well as intra- and extracellular ion and water homeostasis. Over the last decades, a growing number of chloride channels and transporters have been identified in the cells of the pulmonary vasculature and the respiratory tr...

Rationale: Pulmonary hypertension (PH) is a common, yet severe comorbidity in interstitial lung diseases (ILD) such as pulmonary fibrosis (PF), with limited treatment options. Excessive vascular fibrosis and inflammation are often present in PH, but the underlying mechanisms are still not well understood. Objective: To identify a novel functiona...

Objectives Lung vascular and parenchymal changes can be recently assessed quantitatively in thoracic computed tomography (CT) images using automated software tools. We investigated the vessel parameters of patients with Systemic Sclerosis (SSc), quantified by CT imaging, and correlated them with the interstitial lung disease (ILD) features. Method...

The transition from the fetal to the neonatal circulation includes dilatation of the pulmonary arteries (PA) and closure of the Ductus Arteriosus Botalli (DAB). The resting membrane potential and various potassium channel activities in smooth muscle cells (SMC) from fetal and neonatal PA and DAB obtained from the same species has not been systemati...

Background: The potential of microRNAs (miRNAs) as molecular tumor biomarkers for early diagnosis and prognosis in lung cancer is still unclear. Objective: To analyze expression of miRNAs in A549 lung adenocarcinoma (LUAD) cells and in primary, non-malignant bronchial epithelial (BE) cells from healthy donors. To analyze the most prominently der...

The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and...

Systemic sclerosis (SSc) is an autoimmune disease characterised by severe vasculopathy and fibrosis of various organs including the lung. Targeted treatment options for SSc-associated interstitial lung disease (SSc-ILD) are scarce. Here we assessed the effects of pirfenidone in a mouse model of SSc-ILD. Pulmonary function, inflammation and collagen...

The cardiopulmonary hemodynamic profile observed during exercise may identify patients with early stage pulmonary vascular and primary cardiac diseases, and is used clinically to inform prognosis. However, a standardised approach to interpreting hemodynamics is lacking. We performed a systematic literature search according to PRISMA guidelines to i...

Purpose Elevated mean pulmonary arterial pressure (mPAP), or pulmonary hypertension (pH), is associated with vortical blood flow along the main pulmonary artery. We present and validate a method for automated detection and tracking of the PH-related vortex from magnetic resonance 4D flow data that allows estimation of mPAP. Methods The proposed me...

Background Severe pulmonary hypertension (PH) is prognostically highly relevant in patients with COPD. The criteria for severe PH have been defined based on hemodynamic thresholds in right heart catheterization. Research question Can non-invasive clinical tools predict severe PH in COPD patients? How does the mortality risk change with increasing...

Fine control over chloride homeostasis in the lung is required to maintain membrane excitability, transepithelial transport as well as intra- and extracellular ion and water homeostasis. Over the last decades, a growing number of chloride channels and transporters have been identified in the cells of the pulmonary vasculature and the respiratory tr...

Potassium ion concentrations, controlled by ion pumps and potassium channels, predominantly govern a cell′s membrane potential and the tone in the vessels. Calcium-activated potassium channels respond to two different stimuli-changes in voltage and/or changes in intracellular free calcium. Large conductance calcium-activated potassium (BKCa) channe...

Acute respiratory inflammation, most commonly resulting from bacterial or viral infection, is one of the leading causes of death and disability worldwide. The inflammatory lipid mediator prostaglandin D2 (PGD2) and its rate-limiting enzyme, hematopoietic PGD synthase (hPGDS), are well-known drivers of allergic pulmonary inflammation. Here, we sough...

Objective: As real-world data regarding immunotherapy for non-small cell lung cancer are lacking for Austria, we conducted a retrospective study in six hospitals to present data from real-world practice. Methods: Patients with metastatic non-small cell lung cancer were stratified into two groups, either patients with first-line pembrolizumab mon...

The definition of pulmonary hypertension (PH) is based on a growing body of evidence and represents the result of ongoing discussions within the PH community over the past 50 years. In 2018, the most recent World Symposium on Pulmonary Hypertension introduced significant changes in the definition of PH by lowering the mean pulmonary arterial pressu...

Cancer cells frequently lack nutrients like glucose, due to insufficient vascular networks. Mitochondrial phosphoenolpyruvate carboxykinase, PCK2, has recently been found to mediate partial gluconeogenesis and hence anabolic metabolism in glucose starved cancer cells. Here we show that PCK2 acts as a regulator of mitochondrial respiration and maint...

The regulator of G protein signaling (RGS) represents a widespread system of controllers of cellular responses. The activities of the R4 subfamily of RGSs have been elucidated in allergic pulmonary diseases. However, the R4 signaling in other inflammatory lung diseases, with a strong cellular immune response, remained unexplored. Thus, our study ai...