Hans-Juergen Seyfarth

Experience with inhaled iloprost and bosentan in portopulmonary hypertension

Novel treatments, such as prostanoids or endothelin receptor antagonists, have been introduced for various forms of pulmonary arterial hypertension, but the long-term effects of these treatments on portopulmonary hypertension (PPHT) are unknown. In a retrospective analysis, the present authors assessed the safety and efficacy of inhaled iloprost, a prostacyclin analogue, and bosentan, an endothelin receptor antagonist, in patients with PPHT. In total, 31 consecutive patients with Child class A or B cirrhosis and severe PPHT were treated for up to 3 yrs with either inhaled iloprost (n = 13) or bosentan (n = 18), and the effects on exercise capacity, haemodynamics and survival were evaluated. In the iloprost group, the survival rates at 1, 2 and 3 yrs were 77, 62 and 46%, respectively. In the bosentan group, the respective survival rates were 94, 89 and 89%. Event-free survival rates, i.e. survival without transplantation, right heart failure or clinical worsening requiring the introduction of a new treatment for pulmonary hypertension, was also significantly better in the bosentan group. Bosentan had significantly better effects than inhaled iloprost on exercise capacity, as determined by the 6-min walk test, as well as on haemodynamics. Both treatments proved to be safe, especially in regards of liver function. In the present series of patients with well-preserved liver function and severe portopulmonary hypertension, treatment with both inhaled iloprost and bosentan appeared to be safe. Patients treated with bosentan had higher survival rates, but prospective controlled studies are required to confirm these findings.

Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension.

Background Aim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH). Methods Thirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years, mean pulmonary artery pressure, 63±20 mmHg; primary inoperable n = 33, persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period. Efficacy parameters have been evaluated at baseline, after 3 and 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of median 36.4 months (interquartile range 26.6–46.6 months). Results All patients tolerated exercise training without severe adverse events. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 61±54 meters after 3 weeks (p<0.001) and by 71±70 meters after 15 weeks (p = 0.001), as well as scores of quality-of-life questionnaire, peak oxygen consumption and maximal workload. NT-proBNP improved significantly after 3 weeks of exercise training (p = 0.046). The 1-year survival rate was 97%, 2-year survival rate was 94% and the 3-year-survival 86% respectively. Conclusion Training as add-on to medical therapy may be effective in patients with CTEPH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further multicentric randomized controlled studies are needed to confirm these promising results. Trial Registration ClinicalTrials.gov NCT01398345

Inhaled iloprost for the control of pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an elevated pulmonary arterial pressure and vascular resistance with a poor prognosis. Various pulmonary and extrapulmonary causes are now recognized to exist separately from the idiopathic form of pulmonary hypertension. An imbalance in the presence of vasoconstrictors and vasodilators plays an important role in the pathophysiology of the disease, one example being the lack of prostacyclin. Prostacyclin and its analogues are potent vasodilators with antithrombotic, antiproliferative and anti-inflammatory qualities, all of which are important factors in the pathogenesis of precapillary pulmonary hypertension. Iloprost is a stable prostacyclin analogue available for intravenous and aerosolized application. Due to the severe side effects of intravenous administration, the use of inhaled iloprost has become a mainstay in PAH therapy. However, owing to the necessity for 6 to 9 inhalations a day, oral treatment is often preferred as a first-line therapy. Numerous studies proving the efficacy and safety of inhaled iloprost have been performed. It is therefore available for a first-line therapy for PAH. The combination with endothelin-receptor antagonists or sildenafil has shown encouraging effects. Further studies with larger patient populations will have to demonstrate the use of combination therapy for long-term treatment of pulmonary hypertension.

Safety, Tolerability and Clinical Effects of a Rapid Dose Titration of Subcutaneous Treprostinil Therapy in Pulmonary Arterial Hypertension: A Prospective Multi-Centre Trial

Background: Subcutaneous treprostinil has dose-dependent beneficial effects in patients with severe pulmonary arterial hypertension, but adverse effects like infusion site pain can lead to treatment discontinuation. Objectives: The objective of this study was to evaluate safety, tolerability and clinical effects of a rapid up-titration dosing regimen of subcutaneous treprostinil using proactive infusion site pain management. Methods: Effects of rapid up-titration dosing regimen on tolerability and clinical parameters were evaluated in this 16-week, open-label multi-centre study. Results: Thirty-nine patients with idiopathic or heritable pulmonary arterial hypertension on stable treatment with oral pulmonary arterial hypertension-approved drugs (90% on dual combination therapy) were included. Patients achieved a median treprostinil dosage of 35.7 ng/kg/min after 16 weeks. A good overall safety profile was demonstrated with 3 patients (8%) withdrawing due to infusion site pain, which occurred in 97% of patients. After 16 weeks, median 6-min walking distance, cardiac index, pulmonary vascular resistance, and tricuspid annular plane systolic excursion improved. Conclusions: Rapid up-titration of subcutaneous treprostinil was well tolerated, achieving a clinically effective dose associated with improvement of exercise capacity and haemodynamics after 16 weeks. A rapid dose titration regimen and proactive infusion site pain management may improve the handling of this therapy and contribute to better treatment outcome.

Spektrum tuberkulöser Erkrankungen in der pneumologischen Praxis

ZusammenfassungHintergrund:Obgleich in Deutschland im Jahre 2006 die Inzidenz mit 6,6 Neuerkrankungen an Tuberkulose (TB) pro 100 000 Einwohner weiterhin rückläufig ist, bleibt die TB eine Erkrankung von erheblicher epidemiologischer Bedeutung.Patienten und Methodik:Von 04/2001 bis 07/2008 waren 75 Patienten einer internistisch-pneumologischen Praxis wegen einer TB (0,5% aller Patienten) behandelt worden. Die Kriterien einer aktiven TB erfüllten 58 (77,3%), die einer latenten Tuberkuloseinfektion (LTBI) 17 Patienten (22,7%). Der Anteil männlicher Patienten betrug 68,0% (Durchschnittsalter Männer 39,3 ± 16,9 Jahre [Mittelwert ± Standardabweichung], Frauen 46,8 ± 21,5 Jahre; p = nicht signifikant). In Deutschland waren 69,3% der Patienten geboren, 30,7% im Ausland. Einen ausschließlichen Lungenbefall hatten 84,5% Patienten, 8,6% wiesen zusätzliche Organbeteiligungen und 6,9% eine extrapulmonale TB auf. Mikrobiologisch gesichert wurden 62,1% der aktiven TB (51,7% mikroskopisch, 43,1% zusätzlich kulturell, 6,9% ausschließlich kulturell, 19,0% durch Polymerase-Kettenreaktion [PCR]).Ergebnisse:Von 23 Testungen zeigten 52,2% eine volle Sensibilität gegenüber den wichtigsten Erstrangmedikamenten Ethambutol (M), Isoniazid (H), Rifampicin (R), Pyrazinamid (Z) und Streptomycin (S). 13,0% hatten eine Monoresistenz gegen H (4,4%) oder S (8,6%), 4,4% eine Multiresistenz (MDR) gegen R und H, 30,4% eine Polyresistenz (S und H). Die Symptomatik war oft unspezifisch, wurde nicht beachtet oder fehlgedeutet.Schlussfolgerung:Die Diagnosefindung und Therapie einer aktiven oder latenten TB-Erkrankung bleiben weiterhin eine wichtige Aufgabe und Herausforderung, die der effektiven Zusammenarbeit ambulanter, klinischer und behördlicher Gesundheitseinrichtungen bedürfen.AbstractBackground:Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance.Patients and Methods:From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 ± 16.9 years [mean ± standard deviation], women 46.8 ± 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]).Results:Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted.Conclusion:Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.BACKGROUND Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance. PATIENTS AND METHODS From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 +/- 16.9 years [mean +/- standard deviation], women 46.8 +/- 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]). RESULTS Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted. CONCLUSION Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.

Fibrinogen receptor antagonists induce conformational changes of the human platelet glycoprotein IIb

Controversial results have been reported concerning the ability of fibrinogen receptor antagonists (fibans) to induce conformational changes in the fibrinogen receptor after binding to it as the initial step of fibrinogen binding and platelet activation.

Thoracic [18F]fluorodeoxyglucose uptake measured by positron emission tomography/computed tomography in pulmonary hypertension.

AbstractPositron emission tomography (PET) visualizes increased cellular [18F]fluorodeoxyglucose ([18F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [18F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [18F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n = 109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [18F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ≥25 mm Hg (P = 0.013, P = 0.006, P = 0.049, P = 0.002, P = 0.68, respectively) and with PVR ≥480 dyn·s/cm5 (P < 0.001, P = 0.045, P < 0.001, P < 0.001, P = 0.26, respectively). The [18F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r = 0.55, r = 0.42, respectively).Pulmonary and cardiac [18F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [18F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.

Spectrum of tuberculous diseases in a pulmonary outpatient clinic

ZusammenfassungHintergrund:Obgleich in Deutschland im Jahre 2006 die Inzidenz mit 6,6 Neuerkrankungen an Tuberkulose (TB) pro 100 000 Einwohner weiterhin rückläufig ist, bleibt die TB eine Erkrankung von erheblicher epidemiologischer Bedeutung.Patienten und Methodik:Von 04/2001 bis 07/2008 waren 75 Patienten einer internistisch-pneumologischen Praxis wegen einer TB (0,5% aller Patienten) behandelt worden. Die Kriterien einer aktiven TB erfüllten 58 (77,3%), die einer latenten Tuberkuloseinfektion (LTBI) 17 Patienten (22,7%). Der Anteil männlicher Patienten betrug 68,0% (Durchschnittsalter Männer 39,3 ± 16,9 Jahre [Mittelwert ± Standardabweichung], Frauen 46,8 ± 21,5 Jahre; p = nicht signifikant). In Deutschland waren 69,3% der Patienten geboren, 30,7% im Ausland. Einen ausschließlichen Lungenbefall hatten 84,5% Patienten, 8,6% wiesen zusätzliche Organbeteiligungen und 6,9% eine extrapulmonale TB auf. Mikrobiologisch gesichert wurden 62,1% der aktiven TB (51,7% mikroskopisch, 43,1% zusätzlich kulturell, 6,9% ausschließlich kulturell, 19,0% durch Polymerase-Kettenreaktion [PCR]).Ergebnisse:Von 23 Testungen zeigten 52,2% eine volle Sensibilität gegenüber den wichtigsten Erstrangmedikamenten Ethambutol (M), Isoniazid (H), Rifampicin (R), Pyrazinamid (Z) und Streptomycin (S). 13,0% hatten eine Monoresistenz gegen H (4,4%) oder S (8,6%), 4,4% eine Multiresistenz (MDR) gegen R und H, 30,4% eine Polyresistenz (S und H). Die Symptomatik war oft unspezifisch, wurde nicht beachtet oder fehlgedeutet.Schlussfolgerung:Die Diagnosefindung und Therapie einer aktiven oder latenten TB-Erkrankung bleiben weiterhin eine wichtige Aufgabe und Herausforderung, die der effektiven Zusammenarbeit ambulanter, klinischer und behördlicher Gesundheitseinrichtungen bedürfen.AbstractBackground:Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance.Patients and Methods:From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 ± 16.9 years [mean ± standard deviation], women 46.8 ± 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]).Results:Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted.Conclusion:Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.BACKGROUND Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance. PATIENTS AND METHODS From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 +/- 16.9 years [mean +/- standard deviation], women 46.8 +/- 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]). RESULTS Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted. CONCLUSION Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.

Spektrum tuberkulöser Erkrankungen in der pneumologischen Praxis@@@Spectrum of Tuberculous Diseases in a Pulmonary Outpatient Clinic

ZusammenfassungHintergrund:Obgleich in Deutschland im Jahre 2006 die Inzidenz mit 6,6 Neuerkrankungen an Tuberkulose (TB) pro 100 000 Einwohner weiterhin rückläufig ist, bleibt die TB eine Erkrankung von erheblicher epidemiologischer Bedeutung.Patienten und Methodik:Von 04/2001 bis 07/2008 waren 75 Patienten einer internistisch-pneumologischen Praxis wegen einer TB (0,5% aller Patienten) behandelt worden. Die Kriterien einer aktiven TB erfüllten 58 (77,3%), die einer latenten Tuberkuloseinfektion (LTBI) 17 Patienten (22,7%). Der Anteil männlicher Patienten betrug 68,0% (Durchschnittsalter Männer 39,3 ± 16,9 Jahre [Mittelwert ± Standardabweichung], Frauen 46,8 ± 21,5 Jahre; p = nicht signifikant). In Deutschland waren 69,3% der Patienten geboren, 30,7% im Ausland. Einen ausschließlichen Lungenbefall hatten 84,5% Patienten, 8,6% wiesen zusätzliche Organbeteiligungen und 6,9% eine extrapulmonale TB auf. Mikrobiologisch gesichert wurden 62,1% der aktiven TB (51,7% mikroskopisch, 43,1% zusätzlich kulturell, 6,9% ausschließlich kulturell, 19,0% durch Polymerase-Kettenreaktion [PCR]).Ergebnisse:Von 23 Testungen zeigten 52,2% eine volle Sensibilität gegenüber den wichtigsten Erstrangmedikamenten Ethambutol (M), Isoniazid (H), Rifampicin (R), Pyrazinamid (Z) und Streptomycin (S). 13,0% hatten eine Monoresistenz gegen H (4,4%) oder S (8,6%), 4,4% eine Multiresistenz (MDR) gegen R und H, 30,4% eine Polyresistenz (S und H). Die Symptomatik war oft unspezifisch, wurde nicht beachtet oder fehlgedeutet.Schlussfolgerung:Die Diagnosefindung und Therapie einer aktiven oder latenten TB-Erkrankung bleiben weiterhin eine wichtige Aufgabe und Herausforderung, die der effektiven Zusammenarbeit ambulanter, klinischer und behördlicher Gesundheitseinrichtungen bedürfen.AbstractBackground:Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance.Patients and Methods:From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 ± 16.9 years [mean ± standard deviation], women 46.8 ± 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]).Results:Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted.Conclusion:Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.BACKGROUND Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance. PATIENTS AND METHODS From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 +/- 16.9 years [mean +/- standard deviation], women 46.8 +/- 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]). RESULTS Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted. CONCLUSION Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.