[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.

[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.

[Management and Outcome of Surgery in Patients with Severe Pulmonary Hypertension--A Single-Center Experience]. / Management und postoperatives Überleben bei chirurgischen Eingriffen an Patienten mit schwerer pulmonaler Hypertonie--etrospektive Analyse eines Zentrums.

BACKGROUND: Patients with pulmonary hypertension (PH) are at high risk when undergoing surgery. Up to one-third of patients suffer complications; recent studies report a mortality rate of 1 to 7%. Frequent events are deterioration of right heart function and infectious or bleeding complications. METHODS: Data of patients (age ≥ 18) with precapillary PH who need to undergo elective surgery between January 2006 and March 2015 were included in this retrospective analysis. All patients who were planned for surgery underwent the same procedure. First, patients were evaluated in the PH center. Thereafter, PH-relevant data were discussed with the surgeon/anesthesiologist team for risk-adapted planning of anesthesia and intervention. The present analysis comprises patient characteristics and information about surgery and post-interventional course. RESULTS: This study analyzes 31 surgical procedures carried out in PH patients (male: n = 8; PH-group I: n = 23, group III: n = 3, group IV: n = 5, mean age: 59.5 ± 15.3 years). Patients were characterized by compromised hemodynamics and exercise capacity: pulmonary vascular resistance: 805.4 ± 328.5 dyn*s*cm(-5), mean pulmonary arterial pressure: 46.3 ± 9.3 mmHg, 6-minute walking distance: 350.3 ± 123.3 m.The majority of interventions were performed under general anesthesia (n = 24). In 25 cases, the intraoperative monitoring was complemented with right heart catheterization.Eight interventions were associated with complications, three of which were serious. One patient died postoperatively owing to sepsis and right heart failure. CONCLUSION: A careful and structured planning of surgical interventions in patients with PH and the choice of surgical procedure and anesthesia adapted to the conditions of PH might help avoid complications. Further multicentric studies are needed.

[Angiogenin, bFGF and VEGF: angiogenic markers in breath condensate of patients with pulmonary hypertension]. / Die angiogenetischen Faktoren VEGF, Angiogenin und bFGF im Atemkondensat von Patienten mit pulmonaler Hypertonie.

Pulmonary arterial hypertension (PAH) is associated with a change in vascular architecture. A characteristic histological feature is the plexiform lesion. Similar alterations are observed in the pulmonary vascular bed of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Cytokines involved in angiogenesis were found in both serum and lung tissue of patients with PAH and CTEPH, although their role in the formation of plexiform lesions remains unclear. The examination of breath condensate is a noninvasive technique to analyse proteins possibly associated with the pathogenesis of various lung diseases.Breath condensate of 22 patients with pulmonary hypertension (PAH: n = 12; CTEPH: n = 10) and 7 healthy volunteers was examined using a multiplex fluorescent bead immunoassay to determine the concentrations of the biomarkers angiogenin, bFGF, VEGF, IL-8, and TNF-α. Significantly higher levels of angiogenin, bFGF and TNF-α were observed in breath condensate of patients with pulmonary hypertension in comparison to healthy controls. Similarly, breath condensate levels of VEGF were elevated in patients with PAH as against healthy volunteers. However, IL-8 levels in breath condensate did not differ between the two groups. The data suggest that breath condensate of patients with pulmonary hypertension is characterized by increased levels of the angiogenic factors angiogenin, VEGF and bFGF as well as TNF-α, but not IL-8. A larger study is needed to confirm these results and to determine the prognostic and therapeutic implications of these findings.

[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.

[Bilateral pneumothorax following acupuncture]. / Bilateraler Pneumothorax nach Akupunktur.

Acupuncture, a subsection of traditional Chinese medicine, plays an important role as an alternative healing method. Even though there is little proof of its efficacy, acupuncture is becoming more and more popular in the Western world, especially because it is considered almost free of side effects. However, severe complications may occur and have previously been described.We will present a patient who suffered from bilateral pneumothoraces after acupuncture into the paravertebral area. This complication was not considered as a differential diagnosis thus even worsening the patient's life-threatening condition.

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.

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.

[Lymphomatoid granulomatosis--a short description of an unusual case of the disease]. / Lymphomatoide Granulomatose--eine kurze Darstellung der Erkrankung anhand eines aussergewöhnlichen Falles.

Lymphomatoid granulomatosis (LYG) is a rare disease with an unknown pathogenesis. It is considered as a B-cell disorder with an uncertain malignant potential. The disease is classified as an angiocentric and angiodestructive lymphoproliferative disorder. EBV-association (LMP1) and the detection of the surface antigens CD20 and CD30 are the characteristic pathological findings. The lung, the nervous system, the kidneys and the liver are affected most frequently. In the present report the case of a 79-year-old man is described, who showed a cavity in the upper right lobe which was opened out into the trachea. The initial CXR and CT scan demonstrated a large nodular air space opacity (reversed halo sign) on the upper right area and a smaller one on the left side. In addition to CT and bronchoscopy, a surgical biopsy was performed to confirm the diagnosis of lymphomatoid granulomatosis. Treatment consisted in chemotherapy with rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP). Three months after confirmation of diagnosis the patient died of an abscess-forming pneumonia.

[Clinical features and diagnosis of bronchopulmonary infections in the elderly]. / Klinik und Diagnose bronchopulmonaler Infektionen im Alter.

Diseases of the lung are one of the main causes of morbidity and mortality in the elderly. The risk of respiratory infections is increased due to structural changes, malnutrition, co-morbidity, and a variety of other factors. Bacterial and viral pathogens cause acute bronchitis and exacerbations of chronic bronchitis (AECB). Community acquired pneumonias (CAP) show a different spectrum of pathogens and clinical course in comparison to nosocomial pneumonias (hospital acquired pneumonia, HAP). Institutionalised patients are at risk of a health care associated pneumonia (HCAP), with often a different spectrum of pathogens in comparison to CAP and HAP. Elderly patients with cerebrovascular disease and impairment of swallowing or cough reflexes often suffer from aspiration pneumonias. The mortality is highest in the elderly, comorbid, and immunocompromised patient with nosocomial pneumonia. Important preventive measures include influenza and pneumococcal vaccination, avoidance of immobility, oral hygiene, and sufficient nutrition.

Treatment of invasive pulmonary aspergillosis in neutropenic patients by additional bronchoscopic amphotericin B instillation.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a life-threatening condition despite systemic antifungal therapy. OBJECTIVES: This retrospective analysis investigated whether additional bronchoscopic instillation of amphotericin B (amB) would improve efficacy of antifungal treatment in patients with haematological malignancies suffering from IPA. METHODS: Twenty patients (40.6 +/- 14.2 years, 14 male) with preceding chemotherapy, bone marrow or stem cell transplantation complicated by severe IPA who did not respond sufficiently to systemic antifungal therapy were additionally treated by repeated bronchoscopic instillations of amB solution (91 instillations, on average 4.6 +/- 2.2 instillations per patient over a period of 24.1 +/- 21.0 days). Therapeutic response to this combined treatment regimen was monitored by chest X-ray and CT scan. RESULTS: The mean infiltration sizes during systemic antifungal therapy alone (mean duration 11.9 +/- 9.9 days) did not change significantly. However, after additional bronchoscopic instillation of amB solution infiltration sizes were reduced significantly (p < 0.05). A total resolution of infiltrates was seen in 3 and a partial reduction in 13 of 20 patients. Mean duration of total antifungal treatment was 50.1 +/- 24.0 days. The mean follow-up period was 34.1 +/- 31.2 months. The IPA-related mortality rate was 18.8% (3 of 16 patients). CONCLUSIONS: Additional bronchoscopic instillation of amB may improve the efficacy of systemic antifungal therapy in patients with haematological malignancies complicated by severe IPA. Bronchoscopic instillation of amB should be considered as an additional treatment option in cases with IPA unresponsive to systemic therapy.

[Ultrasound guided transthoracic biopsy - safety and efficaces]. / Ultraschall gestützte Biopsie mit Durchleuchtungskontrolle zur Diagnostik thoraxwandnaher Raumforderungen - sicher und diagnostisch effektiv.

BACKGROUND: The biopsy of pulmonary neoplasms localized in close proximity of the thoracic wall and the histological examination of the specimens represent an important diagonstic tool in the work up of benign and malign pulmonary tumours. The biopsy techniques differ with respect to the guiding imaging method, the devices used and the quantity of specimen. This study investigates efficacy and safety of the ultrasound guided transthoracic biopsy. PATIENTS: 46 consecutive patients (n = 37 male; n = 9 female) with a mean age of 64.4 years were included in this analysis. 13 patients suffered from COPD with a mean residual volume in per cent of total lung capacity of 61.9 +/- 12.6 %. 43 pulmonary or pleural and 3 mediastinal neoplasms were investigated. The neoplasm reached the pleura in 41 cases. The mean tumours sizes was 59.1 +/- 30.6 mm. METHOD: The target structure was localized by ultrasound. The ultrasound probe and in its orientation to the target structure was fluoroscopically visualized. Local anaesthesia and sampling were performed in the same orientation under fluoroscopic control. Using the BioPince device (Medical Device Technologies, Inc.; Florida, USA; length 150 mm; Gauge: 18) two to five biopsy cylinders were taken. Chest X-ray was performed within some hours to rule out pneumothorax. RESULTS: The histological examination provided the diagnosis in 44 of 46 cases (95.6 %): lung cancer n = 29, other malign tumours n = 9; benign tumours n = 6). Complications were observed in three patients: haemoptysis, cutaneous emphysema (without need for intervention), pneumothorax with consecutive chest tube placement (one case each). CONCLUSION: The ultrasound guided transthoracic biopsy may be regarded as a safe diagnostic procedure. Complications, even in patients with structural lung disease are in the range of comparable techniques.

[Clinical classification and initial diagnosis of pulmonary hypertension: recommendations of the Cologne Consensus Conference 2016]. / Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: 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 clinical classification and 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 the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

[Decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension]. / Dekompensierte Rechtsherzinsuffizienz, Intensiv- und Perioperativ-Management bei Patienten mit pulmonaler 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 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 management of decompensated right heart failure, intensive care management and perioperative management in patients with pulmonary hypertension. This article summarizes the results and recommendations of the working group on decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension.

[Chronic thromboembolic pulmonary hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). 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 chronic thromboembolic pulmonary hypertension (CTEPH). In every patient with PH of unknown cause CTEPH should be excluded. The primary treatment option is surgical pulmonary endarterectomy (PEA) in a specialized multidisciplinary CTEPH center. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. For balloon pulmonary angioplasty (BPA), there is currently only limited experience. This option - as PEA - is reserved to specialized centers with expertise for this treatment method. In addition, a brief overview is given on pulmonary artery sarcoma, since its surgical treatment is often analogous to PEA. The recommendations of this working group are summarized in the present paper.

[Invasive pulmonary aspergillosis--CT findings in context with the clinical course]. / Invasive Pulmonale Aspergillose--CT-Befunde im Kontext des klinischen Verlaufes.

PURPOSE: To investigate the impact of chest radiographs and CT in patients suffering from invasive pulmonary aspergillosis (IPA) compared to the clinical course. PATIENTS AND METHODS: Twenty-three patients with confirmed diagnosis of IPA between January 1996 and September 1999 were included in this study. Signs of inflammatory infiltrates on chest radiographs and CT were retrospectively evaluated in relation to the onset of the clinical symptoms. Infiltrates on CT were analyzed in detail with respect to number, morphology, and localization. RESULTS: Seventy-six infiltrates were found on the CT of 22 patients; one patient had diffuse areas of lung infiltrates. Both lungs were affected by infiltrates in 14 patients. Pleural effusions were confirmed in 12 patients. Twelve patients had typically round foci with halo and nine patients crescent air signs. The preferred localization of lung infiltrates was segment 6. The median interval between the onset of clinical symptoms and the first radiographic changes was 5.5 days, with an additional interval of 4.5 days until confirmation by CT. Localization, number of infiltrates, and clinical course were not related. CONCLUSION: In immune-compromised patients with fever, a CT of the chest should be carried out as soon as possible to detect signs indicative of IPA. Morphological changes on CT like a round focus with halo and crescent air sign support the diagnosis of IPA. In this context, special attention should be directed to pulmonary segment 6.