[Differential Diagnosis of Pulmonary Hypertension Using the Example of Collagenosis-associated PAH in the Context of Chronic Lung and Left Heart Disease]. / Differenzialdiagnostik der pulmonalen Hypertonie am Beispiel der Kollagenose assoziierten PAH im Kontext chronischer Lungen- und Linksherzerkrankungen.

Pulmonary hypertension (PH) can be diagnosed in the context of connective tissue diseases (CTD) as well as in elderly patients with multiple comorbidities. A correct clinical differential diagnosis and classification is essential before adequate therapeutic decisions can be made. Differential diagnosis of PH in CTD comprises associated pulmonary arterial hypertension (APAH), group 2 or 3 PH (PH arising from left heart or chronic lung disease), chronic thromboembolic PH (PH) and group 5 (e. g. in the context of terminal renal insufficiency). This is also true of elderly patients in whom the decision has to be made if the increasing number of coincident diseases lead to PH or have to be interpreted as comorbidities. In this manuscript, the differential diagnosis of PH is elucidated, focusing on CTD, in the context of left heart disease and chronic lung disease. Furthermore, criteria are presented facilitating an objective approach in this context.

[Complications after Indwelling Pleural Catheter Implant for Symptomatic Recurrent Benign and Malignant Pleural Effusions]. / Komplikationen nach pleuralem getunnelten Dauerkatheter bei symptomatischen rezidivierenden benignen und malignen Pleuraergüssen.

BACKGROUND: Implant of indwelling pleural catheters (IPC) represents an established therapy method in addition to pleurodesis for symptomatic recurrent benign and malignant pleural effusions (BPE and MPE).There are only few studies on IPC safety during follow-up, especially with regard to infection and pneumothorax rates.The aim of our investigation was to determine the complication frequency after IPC implant and its predictive factors in patients with BPE vs. MPE. METHODS: Retrospective analysis of all IPC implantations in the pneumology department at the University Hospital Dresden during 2015 - 2018. RESULTS: An IPC was implanted in 86 patients (43 m/f each; age 66.9 ±â€Š13.3 years) with symptomatic BPE and MPE. BPE and MPE was present in 12.8 % (11/86) and 87.2 % (75/86) of the patients, respectively.A predominantly small and asymptomatic pneumothorax was detectable as an immediate complication in 43/86 (50 %) of patients; 34/43 (79 %) of patients did not require any specific therapy. For 9/43 patients, IPC suction was required for a median period of three days; 8/43 patients had a large pneumothorax with partial or complete regression after a median period of two days.Catheter infection developed in 15.1 % (13/86) of the total group and 36.4 % (4/11) of the BPE vs. 12 % (9/75) of the MPE after a median period of 87 (BPE/MPE 116/87) days. This was more common in BPE (p = 0.035), large pneumothorax (4/8 patients; p = 0.015) and longer catheter dwell times (124 ±â€Š112 vs. 71 ±â€Š112 days; p = 0.07). CONCLUSION: Small pneumothoraxes are frequent after IPC implantation, but usually do not require specific therapy. IPC infection was detected in 15.1 % of all patients after a median period of 87 days. This was more common in patients with BPE, longer catheter dwell times and large pneumothorax.

[Chronic Granulomatous Disease: A Rare Differential Diagnosis in Recurrent Pulmonary Infections in Adults]. / Septische Granulomatose als seltene Differenzialdiagnose rezidivierender pulmonaler Infektionen bei Erwachsenen.

Chronic granulomatous disease (CGD) should be considered as a differential diagnosis in children and adolescents with frequent infections, especially when caused by certain specific pathogens.This case report describes a 64-year-old female with multiple recurrent and complicated bronchopulmonary infections, caused by common, but also rare pathogens, autoimmune phenomena, malignancies and recurrent organizing pneumonia (OP) with granulomas. Finally, the patient was diagnosed with p47phox-deficient chronic granulomatous disease (CGD).Individuals with a primary immunodeficiency may survive multiple complications and may be diagnosed at an advanced age especially if the affected structure shows residual activity. When confronted with patients with recurrent bronchopulmonary infections, especially with certain specific rare pathogens, in combination with organizing pulmonary granulomas as well as autoimmune phenomena, CGD should be considered even in elderly patients. Delayed diagnosis significantly increases mortality and morbidity in such cases.

[Current Aspects of Definition and Diagnosis of Pulmonary Hypertension]. / Aktuelle Definition und Diagnostik der pulmonalen Hypertonie.

At the 6th World Symposium on Pulmonary Hypertension (WSPH), which took place from February 27 until March 1, 2018 in Nice, scientific progress over the past 5 years in the field of pulmonary hypertension (PH) was presented by 13 working groups. The results of the discussion were published as proceedings towards the end of 2018. One of the major changes suggested by the WSPH was the lowering of the diagnostic threshold for PH from ≥ 25 to > 20 mmHg mean pulmonary arterial pressure, measured by right heart catheterization at rest. In addition, the pulmonary vascular resistance was introduced into the definition of PH, which underlines the importance of cardiac output determination at the diagnostic right heart catheterization.In this article, we discuss the rationale and possible consequences of a changed PH definition in the context of the current literature. Further, we provide a current overview on non-invasive and invasive methods for diagnosis, differential diagnosis, and prognosis of PH, including exercise tests.

Clinical Relevance of Computed Tomography Pulmonary Venography.

BACKGROUND: In clinical routine, the pulmonary contrast-enhanced chest computer tomography (CT) is usually focussed on the pulmonary arteries. The purpose of this pictorial essay is to raise the clinicians' awareness for the clinical relevance of CT pulmonary venography. CASE PRESENTATION: A pictorial case series illustrates the clinical consequences of different pulmonary venous pathologies on systemic, pulmonary and bronchial circulation. CONCLUSION: Computed tomography pulmonary venography must be considered before atrial septal defect (ASD) closure and pulmonary lobectomy. Computed tomography pulmonary venography should be considered for patients with right ventricular overload and pulmonary hypertension, as well as for patients with unclear recurrent pulmonary infections, progressive dyspnoea, pleural effusions, haemoptysis, and for patients with respiratory distress after lung-transplantation.

[Dyspnoea in Patients with Pulmonary Hypertension (PH) - a Survey in Spezialized German PH Centres]. / Dyspnoe bei Patienten mit Pulmonaler Hypertonie (PH) - Ergebnisse einer Befragung in deutschen PH-Zentren.

Dyspnoea is the predominant symptom in patients with pulmonary hypertension (PH) at diagnosis. However, since dyspnoea is nonspecific and often occurs in a number of common diseases, the presence of PH can easily be underdiagnosed.In addition, this symptom underlies a high variability in the subjective perception, therefore further diagnostic procedures are often delayed by the patients.A survey of the incidence and severity of dyspnoea in 372 patients with PAH was conducted by questionnaire in German centres. Age, sex distribution and the range of comorbidities corresponded to the findings of national and international registries.Approximately 99 % of patients reported the presence of dyspnoea on exertion, even at low loads.Remarkably, in 13 % of patients dyspnoea occurs as a paroxysmal symptom, which may lead to the differential diagnosis of bronchial asthma. In addition, the patients who were being followed in specialized PH centres reported an increase in dyspnoea during the last year.The results of the survey on the incidence of dyspnoea in patients with PAH are consistent with the findings of international studies.

[Riociguat: stimulator of soluble guanylate-cyclase. New mode of action for the treatment of pulmonary arterial and non operable chronic thromboembolic pulmonary hypertension]. / Riociguat: Stimulation der löslichen Guanylatzyklase. Neuer Wirkmechanismus zur Behandlung der pulmonal-arteriellen und der nicht operablen chronisch thromboembolischen pulmonalen Hypertonie.

Riociguat is the first clinically available soluble Guanylate-cyclase stimulator (sGC) and representative of a completely new class of drugs. Riociguat is approved for pulmonary arterial hypertension (PAH) and non-operable or recurrent/persistent chronic thromboembolic pulmonary hypertension (CTEPH). Moreover, Riociguat is currently under investigation for a wider spectrum of diseases. This article focusses on its mode of action and clinical trial data. Finally, based on these data, the status of approval, as well as the costs a proposal is given how Riociguat can be integrated in the current treatment of PAH and CTEPH.

Ambrisentan improves exercise capacity and symptoms in patients with portopulmonary hypertension.

INTRODUCTION: Ambrisentan, a selective endothelin receptor antagonist has been approved in several countries for pulmonary arterial hypertension. No data have been published on the efficacy of ambrisentan on improvement of exercise capacity in patients with portopulmonary hypertension (PoPH). PATIENTS AND METHODS: We retrospectively analyzed the safety and efficacy of ambrisentan in patients with PoPH in four German university hospitals. RESULTS: 14 patients with moderate to severe PoPH were included. The median follow-up was 16 months (IQR, 12 - 21). 6 minute walk tests after 6 and 12 months improved from 376 meters (IQR, 207 - 440) at baseline to 415 meters (IQR, 393 - 475; p = 0.011) and 413 meters (IQR, 362 - 473, p = 0.005), respectively. WHO- functional class after 1 year of therapy with ambrisentan also improved significantly (p = 0.014). No significant changes in blood gas analysis and liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and international normalized ratio) during therapy with ambrisentan were detectable. CONCLUSIONS: The present study demonstrates significant improvement of exercise capacity and clinical symptoms without relevant safety concerns during ambrisentan treatment in patients with PoPH.

[Pulmonary hypertension due to chronic lung disease. Recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei chronischen Lungenerkrankungen. Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

Adrenal function is related to prognosis in moderate community-acquired pneumonia.

The aim of our study was to prospectively examine adrenal function, including cosyntropin stimulation, and its prognostic value in patients with moderate community-acquired pneumonia (CAP). 59 consecutive adult patients hospitalised on normal wards because of CAP were enrolled. A cosyntropin stimulation test was performed and serum concentrations of C-reactive protein, procalcitonin, interleukin-6, tumour necrosis factor-α, ACTH, cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) were measured. Predefined outcome parameters were clinical instability after 72 h, mortality and combined intensive care unit (ICU) admission or mortality. Critical illness-related corticosteroid insufficiency (CIRCI) occurred in six patients (10.3%). Cortisol, age-corrected DHEA, ACTH and the DHEA/DHEAS ratio were elevated in patients remaining unstable after 72 h. In multivariate analysis, cortisol (p = 0.03), ACTH (p = 0.04) and the pneumonia severity index (PSI) score (p = 0.005) independently predicted clinical instability after 72 h, and only cortisol predicted mortality (p = 0.04) and combined ICU-admission or mortality (p = 0.006). The predictive value of serum cortisol after receiver operating characteristic curve analysis equalled that of the PSI score. Patients with serum cortisol >734 nmol·L(-1) had a high probability for mortality (OR 38.3; p = 0.002). CIRCI is rare in patients with moderate CAP. Adrenal function is related to the prognosis of CAP. The diagnostic accuracy of serum cortisol equals that of the PSI score. Serum cortisol should be evaluated within clinical prediction scores on larger studies.

Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study.

We assessed the therapeutic potential of riociguat, a novel soluble guanylate cyclase stimulator, in adults with chronic thromboembolic pulmonary hypertension (CTEPH; n = 42) or pulmonary arterial hypertension (PAH; n = 33) in World Health Organization (WHO) functional class II/III. In this 12-week, multicentre, open-label, uncontrolled phase II study, patients received oral riociguat 1.0-2.5 mg t.i.d. titrated according to systemic systolic blood pressure (SBP). Primary end-points were safety and tolerability; pharmacodynamic changes were secondary end-points. Riociguat was generally well tolerated. Asymptomatic hypotension (SBP <90 mmHg) occurred in 11 patients, but blood pressure normalised without dose alteration in nine and after dose reduction in two. Median 6-min walking distance increased in patients with CTEPH (55.0 m from baseline (390 m); p<0.0001) and PAH (57.0 m from baseline (337 m); p<0.0001); patients in functional class II or III and bosentan pre-treated patients showed similar improvements. Pulmonary vascular resistance was significantly reduced by 215 dyn·s·cm(-5) from baseline (709 dyn·s·cm(-5); p<0.0001). 42 (56%) patients were considered to have experienced drug-related adverse events (AEs; 96% mild or moderate). Dyspepsia, headache and hypotension were the most frequent AEs. Study discontinuation because of AEs was 4%. These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity, symptoms and pulmonary haemodynamics in CTEPH and PAH. Randomised controlled trials are underway.

[Current concepts for the microbiological detection of airway pathogens]. / Aktuelle Konzepte zum mikrobiologischen Nachweis von Atemwegserregern.

The frequency and range of bacterial pathogens in respiratory tract infections depends on a variety of variables. The aetiology is influenced by the type of respiratory tract infection (acute bronchitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia, nosocomial pneumonia), geographic and seasonal factors, and by the diagnostic methods implemented to identify the pathogens. Furthermore, there exists a considerable uncertainty concerning the clinical relevance of positive bacteriological findings in respiratory secretions because they are retrieved from non-sterile or contaminated environments. To differentiate infection from contamination, both microbiological and clinical findings have to be assessed, which might be difficult in the setting of systemic or local immunosuppression.

[Pulmonary complications of liver cirrhosis: hepatopulmonary syndrome, portopulmonary hypertension and hepatic hydrothorax]. / Pulmonale Komplikationen der Leberzirrhose: hepatopulmonales Syndrom, portopulmonale Hypertonie und hepatischer Hydrothorax.

Hepatopulmonary syndrome, portopulmonary hypertension and hepatic hydrothorax are typical pulmonary complications in patients with liver cirrhosis. Whereas hepatopulmonary syndrome and portopulmonary hypertension represent pulmonary vascular diseases, the development of hepatic hydrothorax is associated with the presence of ascites and phrenic lesions. For severe hepatopulmonary syndrome and refractory hepatic hydrothorax, liver transplantation is the treatment of choice. In severe portopulmonary hypertension specific medical treatment is indicated. In selected patients, beside intravenous prostanoids, oral endothelin receptor antagonists and phosphodiesterase type-5 inhibitors are possible treatment options.

Long-term outcome with intravenous iloprost in pulmonary arterial hypertension.

There is limited data on the long-term efficacy of intravenous iloprost in patients with pulmonary arterial hypertension (PAH). This retrospective multicentre analysis evaluated the clinical course of patients with PAH treated with i.v. iloprost, in most cases after having received inhaled iloprost as first-line therapy. Between 1997 and 2001, 79 PAH patients were treated with i.v. iloprost and followed until 2007. These patients had advanced and progressive disease as indicated by a mean pulmonary vascular resistance of 1,533 dyn x s x cm(-5) at the time of diagnosis and of 1,858 dyn x s x cm(-5) at the onset of i.v. iloprost therapy. Introduction of i.v. iloprost therapy resulted in initial haemodynamic and clinical improvement. At the end of the observation period, however, 50 (61%) patients had died and 21 (26%) required lung transplantation. Transplantation-free survival rates at 1, 3, and 5 yrs were 86%, 59% and 45%, respectively, after the diagnosis of PAH, and 54%, 31% and 15%, respectively, after the introduction of i.v. iloprost therapy. Predictors of an adverse outcome at baseline were a low 6-min walk distance and a low mixed venous oxygen saturation. In conclusion, despite initial haemodynamic and clinical improvement, overall long-term survival with i.v. iloprost therapy was limited.

L-arginine plasma levels and severity of idiopathic pulmonary arterial hypertension.

BACKGROUND: Idiopathic pulmonary arterial hypertension (iPAH) is a rare disease of unknown aetiology characterized by a poor prognosis. Impairment of nitric oxide (NO) synthesis or NO-induced vasorelaxation has been suspected to play a role in the development of iPAH. This study was performed to investigate possible correlations between the plasma levels of the NO-related aminoacids L-arginine, L-citrulline and N-hydroxy-L-arginine (L-NHA) and the severity of iPAH. METHODS: In twelve iPAH patients hemodynamics were measured by right heart catheterization, and plasma levels of L-arginine, L-citrulline and L-NHA were determined in blood samples from the pulmonary artery, peripheral artery and peripheral vein by high-performance liquid chromatography analysis. In eight of twelve patients a six minute walk test was performed. RESULTS: Plasma levels of L-arginine strongly correlated to right atrial pressure, cardiac output, cardiac index, mixed-venous oxygen saturation, six minute walk data and NYHA functional class at all sites of blood sampling (p < 0.05). CONCLUSIONS: The results suggest a possible role of the NO precursor L-arginine in the pathogenesis of iPAH.

[Risk stratification and follow-up assessment of patients with pulmonary arterial hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Risikostratifizierung und Verlaufskontrollen bei PAH-Patienten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to risk stratification and follow-up assessment of patients with PAH. This manuscript summarizes the results and recommendations of this working group.

[General and supportive therapy of pulmonary arterial hypertension]. / Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.

[Targeted therapy of pulmonary arterial hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Gezielte Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensuskonferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the targeted therapy of PAH. This article summarizes the results and recommendations of the working group on targeted treatment of PAH.

[Pulmonary hypertension due to chronic lung disease: Recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Lungenkrankheiten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.