85 results on '"Hanno Leuchte"'
Search Results
2. Der Rechtsherzkatheter - Schritt für Schritt
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Tobias J. Lange, Hanno Leuchte, and Matthias Held
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Pulmonary and Respiratory Medicine - Published
- 2022
3. Quality of Life 3 and 12 Months Following Acute Pulmonary Embolism
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Hanno Leuchte, Hans-Jürgen Seyfarth, Felix Gerhardt, Stefano Barco, Philipp S. Wild, Frederikus A. Klok, Michael Halank, Stephan Rosenkranz, Marius Jankowski, Ralf Ewert, F. Joachim Meyer, Stavros Konstantinides, Mareike Lankeit, Claus Neurohr, Heinrike Wilkens, Hossein Ardeschir Ghofrani, Marius M. Hoeper, Julia Freise, Matthias Held, Luca Valerio, Martin Faehling, Ekkehard Grünig, R Wachter, Eckhard Mayer, Franziska C. Trudzinski, Kai-Helge Schmidt, Leonhard Bruch, and Christian Opitz
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Visual analogue scale ,Patient-centered outcomes ,Critical Care and Intensive Care Medicine ,medicine.disease ,humanities ,Pulmonary embolism ,Clinical trial ,Quality of life ,Interquartile range ,Internal medicine ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Cohort study ,Cardiopulmonary disease - Abstract
BACKGROUND Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact of baseline characteristics using multivariable mixed effects linear regression were studied; also assessed was the course of generic QoL as evaluated by using the EuroQoL Group 5-Dimension 5-Level utility index and the EuroQoL Visual Analog Scale. RESULTS In 620 patients (44% women; median age, 62 years), overall disease-specific QoL improved from 3 to 12 months, with a decrease in the median PEmb-QoL score from 19.4% to 13.0% and a mean individual change of -4.3% (95% CI, -3.2 to -5.5). Female sex, cardiopulmonary disease, and higher BMI were associated with worse QoL at both 3 and 12 months. Over time, the association with BMI became weaker, whereas older age and previous VTE were associated with worsening QoL. Generic QoL also improved: the mean ± SD EuroQoL Group 5-Dimension 5-Level utility index increased from 0.85 ± 0.22 to 0.87 ± 0.20 and the visual analog scale from 72.9 ± 18.8 to 74.4 ± 19.1. INTERPRETATION In a large cohort of survivors of acute PE, the change of QoL was quantified between months 3 and 12 following diagnosis, and factors independently associated with lower QoL and slower recovery of QoL were identified. This information may facilitate the planning and interpretation of clinical trials assessing QoL and help guide patient management. CLINICAL TRIAL REGISTRATION German Clinical Trials Registry (Deutsches Register Klinischer Studien: www.drks.de); No.: DRKS00005939.
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- 2021
4. Differenzialdiagnostik der pulmonalen Hypertonie am Beispiel der Kollagenose assoziierten PAH im Kontext chronischer Lungen- und Linksherzerkrankungen
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Hans-Jürgen Seyfarth, M Halank, Hans Klose, H Wilkens, M Held, Mathias M. Borst, Tobias J. Lange, Ralf Ewert, F. J. Meyer, Dirk Skowasch, and Hanno Leuchte
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Pulmonary and Respiratory Medicine ,Gynecology ,medicine.medical_specialty ,Lung ,business.industry ,Context (language use) ,030204 cardiovascular system & hematology ,medicine.disease ,Pulmonary hypertension ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030228 respiratory system ,Medicine ,Left heart disease ,business - Abstract
ZusammenfassungDie pulmonale Hypertonie (PH) ist eine regelmäßige Komplikation von Kollagenosen und wird zudem im Zusammenhang mit Lungen- und Linksherzerkrankungen diagnostiziert. Die korrekte Differenzierung und Klassifikation der PH ist essenziell, um Therapien möglichst zielgerichtet einsetzen zu können und ein Vorenthalten von wichtigen Therapien ebenso zu vermeiden wie eine Übertherapie.Bei den Kollagenosen umfasst die Differenzialdiagnostik und Klassifikation die Differenzierung innerhalb der assoziierten pulmonalarteriellen Hypertonie (APAH) Gruppe 1, aber auch, Klassifikationsgruppen übergreifend, die Gruppe 2 (mit führender linkskardialer Beteiligung), Gruppe 3 (mit führender parenchymatöser Lungenerkrankung), Gruppe 4 (chronisch thromboembolische PH) und letztlich die Gruppe 5 (z. B. bei terminaler Niereninsuffizienz und Dialysepflicht). Ähnliches trifft auch auf die zunehmend älteren Patienten zu, die mit einer PAH diagnostiziert werden und Komorbiditäten aufweisen, die entweder selbst eine PH hervorrufen können oder als Komorbiditäten einer echten PAH auftreten. Die abnehmende Trennschärfe zwischen den einzelnen PH-Gruppen erschwert die korrekte Klassifikation und stellt eine große klinische Herausforderung dar. Auf dem Boden unterschiedlicher klinischer Szenarien wird im vorliegenden Artikel die Differenzialdiagnostik der PH sowohl bei Kollagenosen als auch bei chronischen Linksherz- und Lungenerkrankungen aufgearbeitet und objektive Kriterien vorgestellt, die diese Differenzierung erleichtern.
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- 2021
5. Aktuelle Definition und Diagnostik der pulmonalen Hypertonie
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Tobias J. Lange, Hanno Leuchte, M Halank, Hans-Jürgen Seyfarth, F. J. Meyer, Dirk Skowasch, R Ewert, H Wilkens, Hans Klose, M Held, and Mathias M. Borst
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Pulmonary and Respiratory Medicine ,Gynecology ,medicine.medical_specialty ,Philosophy ,medicine - Abstract
ZusammenfassungDie 6. Weltkonferenz für pulmonale Hypertonie (PH) fand vom 27. 2. – 1. 3. 2018 in Nizza statt. Hier wurden die Erkenntnisse auf dem Gebiet der PH der letzten 5 Jahre nach Aufarbeitung und Diskussion über einen längeren Vorbereitungszeitraum von 13 Arbeitsgruppen präsentiert und in der Folge zum Jahreswechsel 2018/2019 publiziert. Einer der seither intensiv diskutierten Vorschläge ist der einer Änderung der hämodynamischen Definition der PH mit Absenkung des Grenzwertes für den mittleren pulmonalarteriellen Druck von ≥ 25 auf > 20 mmHg, gemessen im Rechtsherzkatheter in Ruhe. Zusätzlich wurde der pulmonalvaskuläre Widerstand in die PH-Definition aufgenommen, was die Wichtigkeit der Bestimmung des Herzzeitvolumens während der Rechtsherzkatheteruntersuchung unterstreicht.Die Rationale sowie mögliche Auswirkungen der neuen PH-Definition, zu welchen zwischenzeitlich bereits neue Publikationen erschienen sind, möchten wir in diesem Übersichtsartikel diskutieren. Ferner ist ein aktueller Überblick zur nicht-invasiven und invasiven Diagnostik der PH enthalten, in welchem auf den Stellenwert der Methoden für Diagnostik, Differenzialdiagnostik und Prognose sowie weitere Neuerungen der 6. PH-Weltkonferenz eingegangen wird. Ergänzt haben wir einen Abschnitt zum Stellenwert von Belastungsuntersuchungen für das Erkennen und die Verlaufsbeurteilung der PH, welche bei der Diskussion in Nizza und in den nachfolgenden Publikationen zumindest erwähnt, aber nicht ausführlicher besprochen wurden.
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- 2020
6. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study
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Athol U. Wells, Marius M. Hoeper, Fernando J. Martinez, Wim A. Wuyts, Tamera J. Corte, Silvia Ulrich, Hanno Leuchte, Harold R. Collard, Nesrin Mogulkoc, Francis Boateng, Vincent Cottin, Anne Keogh, Jürgen Behr, Steven D. Nathan, and Zhen Yao
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Hypertension, Pulmonary ,Population ,Enzyme Activators ,Placebo ,Riociguat ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Idiopathic Interstitial Pneumonias ,030212 general & internal medicine ,Adverse effect ,education ,Idiopathic interstitial pneumonia ,Aged ,education.field_of_study ,business.industry ,Interstitial lung disease ,medicine.disease ,Pulmonary hypertension ,Pyrimidines ,Treatment Outcome ,Blood pressure ,030228 respiratory system ,Pyrazoles ,Female ,business ,medicine.drug - Abstract
Summary Background Idiopathic interstitial pneumonias are often complicated by pulmonary hypertension, increasing morbidity and mortality. There are no approved treatments for pulmonary hypertension associated with idiopathic interstitial pneumonia (PH-IIP). We aimed to evaluate the efficacy and safety of riociguat in patients with PH-IIP. Methods RISE-IIP was a double-blind, randomised, placebo-controlled study done at 65 pulmonary hypertension and interstitial lung disease centres in 19 countries to evaluate the efficacy and safety of riociguat in patients with PH-IIP. Eligible patients were adults (aged 18–80 years) diagnosed with idiopathic interstitial pneumonia (as per American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines), forced vital capacity (FVC) of at least 45%, 6MWD of 150–450 m, WHO functional classes II–IV, precapillary pulmonary hypertension confirmed by right heart catheterisation, systolic blood pressure of at least 95 mm Hg, and no signs or symptoms of hypotension. Patients were randomly allocated (1:1) using an interactive voice and web response system to riociguat (0·5–2·5 mg three times daily) or placebo for 26 weeks (main study), after which they could enter an open-label extension in which all patients received riociguat. The primary endpoint was change in 6-min walking distance (6MWD) in the intention-to-treat population. Prespecified safety variables included adverse events and serious adverse events, laboratory parameters, and adverse events of special interest (haemoptysis and symptomatic hypotension), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02138825. Findings Between June 4, 2014, and May 5, 2016, we enrolled 229 participants. After the exclusion of 82 participants, 147 were randomly allocated to treatment (73 to riociguat, 74 to placebo). The study was terminated early (median treatment duration 157 days [range 6–203]) at the request of the data monitoring committee owing to increased serious adverse events (main study: 27 [37%] of 73 participants in the riociguat group vs 17 [23%] of 74 in the placebo group) and mortality in patients receiving riociguat, and the absence of efficacy signals in the riociguat group. 11 patients died in the main study (eight in the riociguat group, three in the placebo group), and nine died in the extension phase (one in the riociguat group, eight in the former placebo group; all received riociguat). In the main study, the most common adverse events were peripheral oedema (16 [22%] of 73 in the riociguat group vs seven [9%] of 74 in the placebo group) and diarrhoea (11 [15%] vs seven [9%]). The most common serious adverse events were worsening of interstitial lung disease (main study: six [8%] of 73 in the riociguat group vs five [7%] of 74 in the placebo group) and pneumonia (four [5%] vs one [1%]). Riociguat did not improve 6MWD versus placebo at 26 weeks (least-squares mean difference 21 m; 95% CI −9 to 52). Interpretation In patients with PH-IIP, riociguat was associated with increased serious adverse events and mortality, and an unfavourable risk–benefit profile. Riociguat should not be used in patients with PH-IIP. Funding Bayer AG and Merck & Co.
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- 2019
7. Hämodynamische Definition der pulmonalen Hypertonie: Kommentar zu der vorgeschlagenen Änderung durch das 6th World Symposium on Pulmonary Hypertension
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Gerhard-Paul Diller, Heinrike Wilkens, Horst Olschewski, Hans Klose, Matthias Held, Eckhard Mayer, Werner Seeger, Michael Halank, Stavros Konstantinides, Marius M. Hoeper, Ralf Ewert, H. Ardeschir Ghofrani, Tobias J. Lange, Ekkehard Grünig, Hanno Leuchte, Stephan Rosenkranz, K Olsson, Harald Kaemmerer, Gabor Kovacs, Daniel Dumitrescu, Andrea Olschewski, I. Lang, Christian Opitz, and Ralph Schermuly
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Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,030228 respiratory system ,business.industry ,Medicine ,General Medicine ,030204 cardiovascular system & hematology ,business ,ddc - Abstract
ZusammenfassungDie Ende 2015 veröffentlichten ESC/ERS-Leitlinien und andere internationale Empfehlungen definierten die pulmonale Hypertonie (PH) bisher durch einen invasiv gemessenen mittleren pulmonal arteriellen Druck (mPAP) ≥ 25 mmHg in Ruhe. Auf dem 6th World Symposium on Pulmonary Hypertension in Nizza wurde eine Modifikation dieser hämodynamischen Definition im Sinne einer Senkung des Schwellenwertes auf > 20 mmHg vorgeschlagen. Für die präkapilläre PH wird zusätzlich ein pulmonaler Gefäßwiderstand (PVR) ≥ 3 Wood-Einheiten (WE) gefordert. Diese Änderung muss im Hinblick auf die zugrunde liegende Rationale und mögliche Konsequenzen kritisch hinterfragt werden; es bedarf daher einer eingehenden Erläuterung. Insbesondere muss klargestellt werden, dass diese Änderung aktuell keinen Einfluss auf die evidenzbasierte und zulassungskonforme Verschreibung von Medikamenten zur gezielten Therapie der pulmonal arteriellen Hypertonie (PAH) hat.
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- 2019
8. Functional outcomes and quality of life during long-term follow-up after acute pulmonary embolism: analysis of the prospective multicentre FOCUS study
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Claus Neurohr, Hans-Jürgen Seyfarth, Focus Investigators, Frederikus A. Klok, Philipp S. Wild, Christian Opitz, Eckhard Mayer, Heinrike Wilkens, Luca Valerio, Marius Jankowski, Stefano Barco, F.J Meyer, R Wachter, Hanno Leuchte, Marius M. Hoeper, and Franziska C. Trudzinski
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medicine.medical_specialty ,Quality of life ,Long term follow up ,business.industry ,Symptom persistence ,medicine ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,Intensive care medicine ,Venous thromboembolism ,Pulmonary embolism - Abstract
Background It is unclear to which extent persistence of symptoms and/or residual haemodynamic impairment clinical course of pulmonary embolism are associated with worse quality of life (QoL). Aims To study the correlation between symptoms and haemodynamic impairment with QoL during the first year after acute pulmonary embolism (PE). Methods The Follow-Up after acute pulmonary embolism (FOCUS) study prospectively enrolled and followed consecutive adult patients diagnosed with acute symptomatic objectively diagnosed PE. In the present analysis, we considered patients who completed the Pulmonary Embolism QoL (PEmb-QoL) Questionnaire at predefined visits 3 and 12 months after acute PE. The PEmb-QoL score ranges from 0% (best QoL) to 100% (worst QoL). We evaluated at these two time points the correlation between persisting symptoms (group: symptoms), elevation of natriuretic peptides or residual right ventricular dysfunction (group: RVD), or their combination (group: symptoms + RVD) and QoL. Results A total of 617 patients were included; their median age was 62 years, 44% were women; 8% had active cancer, and 21% previous venous thromboembolism. At 3 months, patients with neither symptoms nor RVD (n=302) had the highest quality of life (median score 18%, 25th–75th percentile: 8%–34%), followed by those without symptoms but with RVD (n=255; median score 19%, 25th–75th percentile: 7%–34%), and by those with symptoms only (n=131; median PEmb-QoL 31%, 25th–75th percentile: 18%–49%). Patients with both symptoms and RVD (n=170) had the worst quality of life (median score 38%, 25th–75th percentile: 19%–53%); Figure 1A. At 12 months, we found an overall improvement of PEmb-QoL score. The degree of this QoL improvement varied across groups, being largest for patients who recovered from having symptoms + RVD at 3 months to normalization of at least one at 12 months. The change in QoL from 3 to 12 months was smaller both in patients who had neither symptoms nor RVD and in patients who had no recovery in either symptoms or RVD; Figure 1B. Conclusions Persistent symptoms after PE, especially in patients with elevated biomarkers or residual echocardiographic dysfunction, were the main drivers of QoL at 3 months as well as of the course of QoL over time. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): University Medical Center of the Johannes Gutenberg University, Mainz, Germany; German Federal Ministry of Education and Research
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- 2020
9. Impact of lung morphology on clinical outcomes with riociguat in patients with pulmonary hypertension and idiopathic interstitial pneumonia: A post hoc subgroup analysis of the RISE-IIP study
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Steven D. Nathan, Sylvia Nikkho, Tamera J. Corte, Zhen Yao, Dennis Busse, Juergen Behr, Frank-Detlef Scholle, Fernando J. Martinez, Ullrich Müller-Lisse, Silvia Ulrich, Vincent Cottin, Günther Brüggenwerth, Nesrin Mogulkoc, Athol U. Wells, Marius M. Hoeper, Julia Ley-Zaporozhan, Anne Keogh, Wim A. Wuyts, Hanno Leuchte, University of Zurich, and Nathan, Steven D
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Male ,2747 Transplantation ,high-resolution computed tomography ,Vital Capacity ,Combined Pulmonary Fibrosis And Emphysema ,High-resolution Computed Tomography ,Riociguat ,0302 clinical medicine ,Diffusing capacity ,Forced Expiratory Volume ,Lung volumes ,030212 general & internal medicine ,Lung ,medicine.diagnostic_test ,respiratory system ,Prognosis ,Combined pulmonary fibrosis and emphysema ,2746 Surgery ,medicine.anatomical_structure ,riociguat ,Cardiology ,Female ,10178 Clinic for Pneumology ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,High-resolution computed tomography ,Hypertension, Pulmonary ,610 Medicine & health ,Clinical trials registration. NCT02138825 ,2705 Cardiology and Cardiovascular Medicine ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Idiopathic Interstitial Pneumonias ,Pulmonary Wedge Pressure ,Idiopathic interstitial pneumonia ,Aged ,Retrospective Studies ,Emphysema ,Transplantation ,Dose-Response Relationship, Drug ,business.industry ,pulmonary hypertension associated with idiopathic interstitial pneumonia ,medicine.disease ,Fibrosis ,Pulmonary hypertension ,Pyrimidines ,030228 respiratory system ,2740 Pulmonary and Respiratory Medicine ,Stimulation ,Pyrazoles ,Surgery ,business ,Tomography, X-Ray Computed ,combined pulmonary fibrosis and emphysema - Abstract
Background: Riociguat in Patients with Symptomatic Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (RISE-IIP), a randomized, controlled, phase 2b trial of riociguat for pulmonary hypertension associated with idiopathic interstitial pneumonia, was terminated early due to increased mortality in riociguat-treated patients. Baseline characteristics of enrolled patients demonstrated a low diffusing capacity of the lung for carbon monoxide (DLCO) with preserved lung volumes at baseline, suggesting the presence of combined pulmonary fibrosis and emphysema (CPFE) in some patients. This post hoc analysis of RISE-IIP was undertaken to explore lung morphology, assessed by high-resolution computed tomography, and associated clinical outcomes. Methods: Available baseline/pre-baseline high-resolution computed tomography scans were reviewed centrally by 2 radiologists. The extent of emphysema and fibrosis was retrospectively scored and combined to provide the total CPFE score. Results: Data were available for 65/147 patients (44%), including 15/27 fatal cases (56%). Of these, 41/65 patients (63%) had CPFE. Mortality was higher in patients with CPFE (12/41; 29%) than those without (3/24; 13%). Fourteen patients with CPFE had emphysema > fibrosis (4 died). No relationship was observed between CPFE score, survival status, and treatment assignment. A low DLCO, short 6-min walking distance, and high forced vital capacity:DLCO ratio at baseline also appeared to be risk factors for mortality. Conclusions: High parenchymal lung disease burden and the presence of more emphysema than fibrosis might have predisposed patients with pulmonary hypertension associated with idiopathic interstitial pneumonia to poor outcomes in RISE-IIP. Future studies of therapy for group 3 pulmonary hypertension should include centrally adjudicated imaging for morphologic phenotyping and disease burden evaluation during screening. © 2021 The Authors, Ikaria Sanofi Inova Health System Roche University of Texas Southwestern Medical Center Gilead Sciences AstraZeneca Boehringer Ingelheim, BI Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF United Therapeutics Corporation Merck Sharp and Dohme, MSD Novartis Sunovion Actelion Pharmaceuticals Pfizer National Institutes of Health, NIH GlaxoSmithKline, GSK National Heart, Lung, and Blood Institute, NHLBI Lunge Zürich Bayer Merck Sharp and Dohme, MSD, The authors have reported to the Journal of Heart and Lung Transplantation the following: S. D. Nathan reports consultation fees and Inova Fairfax Hospital receiving research funding for work pertaining to the RISE-IIP study from Bayer AG. V. Cottin reports grants from Actelion, Boehringer Ingelheim, GSK, Pfizer, and Roche, and personal fees from Bayer AG, Biogen Idec, Boehringer Ingelheim, Gilead, GSK, Intermune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Sanofi. J. Behr reports receiving personal fees from Actelion, Bayer AG, Biogen, BMS, Boehringer Ingelheim, Galapagos, and Roche for consulting and lectures. M. M. Hoeper reports consultancy fees from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG, Pfizer, and Merck Sharp & Dohme. F. J. Martinez reports grants from National Institutes of Health and National Heart, Lung and Blood Institute, and support from Academic CME, Amgen, Annenberg, AstraZeneca, ATS, Axon, Axon Communication, Biogen, Bioscale, Boehringer Ingelheim, California Society for Allergy and Immunology, Carden Jennings, Centocor, CME Incite, CSA Medical, Falco, Forest, Genentech, Genzyme, GSK, Gilead, Inova Health System, Haymarket Communications, Ikaria, Informa, Integritas, InThought, Ikaria/Bellerophon, Janssen, Johnson & Johnson, Kadmon, MedScape, Merck, Miller Medical, National Association for Continuing Education, Novartis, Nycomed/Takeda, Paradigm, Pearl, Peer Voice, Pfizer, Promedior, Roche, Spectrum Health System, St John's Hospital, St Mary's Hospital, Sunovion, Theravance, University of Texas Southwestern, Unity Biotechnology, UpToDate, Western Society of Allergy and Immunology, Vertex, and Veracyte. T. J. Corte reports grants and personal fees from Boehringer Ingelheim and Roche, grants from Bayer AG, Gilead, and Intermune, and personal fees from AstraZeneca. A. M. Keogh reports grants and personal fees from Bayer AG. H. Leuchte reports personal fees from Actelion, Bayer AG, GSK, Merck Sharp & Dohme, and Pfizer, and nonfinancial support from Bayer AG. N. Mogulkoc reports receiving personal fees from Boehringer Ingelheim, Roche, Actelion, Bayer AG, and Nobel for consulting and lectures. S. Ulrich reports personal fees from Actelion and Bayer AG, and grants from Swiss National Science Foundation, United Therapeutics, and Zurich Lung League. W. A. Wuyts reports grants from Boehringer Ingelheim, FWO Flanders, Roche, and National Institutes of Health. Z. Yao was an employee of Bayer AG during the conduct of the RISE-IIP study. J. Ley-Zaporozhan reports consultation fees from Bayer AG and Boehringer Ingelheim. U. G. Müller-Lisse reports no conflicts of interest. F-D. Scholle, G. Brüggenwerth, and S. Nikkho were employees of Bayer AG during the conduct of the RISE-IIP study. D. Busse was an employee of Chrestos Concept GmbH & Co. during the development of this manuscript. A. U. Wells reports personal fees from Bayer AG, Roche, and Boehringer Ingelheim., The RISE-IIP study was funded by Bayer AG, Berlin, Germany, and Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. D.B. performed statistical analyses, funded by Bayer AG, Berlin, Germany.
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- 2020
10. Differenzialdiagnostik der pulmonalen Hypertonie
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Daniel Dumitrescu, Michael Halank, and Hanno Leuchte
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03 medical and health sciences ,0302 clinical medicine ,030212 general & internal medicine ,General Medicine ,030204 cardiovascular system & hematology - Abstract
ZusammenfassungDie pulmonale Hypertonie (PH) ist per se keine Erkrankung, sondern ein hämodynamischer Zustand, der eine Druckerhöhung im kleinen Kreislauf in Ruhe beschreibt. Ursächlich können hierfür viele Erkrankungen verantwortlich sein. Unabhängig von der Ätiologie der PH ist deren führendes Symptom die progrediente Dyspnoe, die nicht selten gleichzeitig mit Müdigkeit und Abgeschlagenheit einhergeht. Aufgrund des unspezifischen Charakters der Beschwerden vergehen häufig Monate bis Jahre bis zur Diagnosestellung. Bei kardialer Dekompensation sind Halsvenenstauung, Beinödeme und Aszites typische klinische Zeichen der rechtskardialen Vorlast-Erhöhung. Die wichtigste nichtinvasive Untersuchungsmethode zur Verdachtsdiagnose der PH ist in den meisten Fällen die Echokardiografie. Zur Basisdiagnostik der Belastungsdyspnoe unklarer Ätiologie zählen neben der körperlichen Untersuchung und Anamnese, die Lungenfunktions-Untersuchung einschließlich alveolo-kapillärer Diffusionsmessung, die Bestimmung der kapillären oder arteriellen Blutgase, die Röntgenaufnahme der Lunge, das EKG, laborchemische Herzinsuffizienzmarker und die Spiroergometrie. Die häufigsten Ursachen der PH sind Linksherz- und/oder Lungenerkrankungen. Aktuell erfolgt eine klinische Einteilung der pulmonalen Hypertonie in 5 Gruppen. Da die PH unabhängig von der Ätiologie mit einer Beeinträchtigung der Prognose assoziiert ist, sind die Hauptziele der Diagnostik die exakte Klassifikation der Erkrankung und deren Früherkennung, um einen verzögerten Therapiebeginn zu verhindern. Nicht immer ist die exakte Klärung der Ursache der PH im Einzelfall möglich. Wenn Lungen- und Linksherzerkrankungen als Ursachen der PH ausgeschlossen sind, sollte eine Ventilations-/Perfussionszintigrafie und eine Überweisung an ein PH-Zentrum erfolgen. Dort sollte dann nach den seltenen Ursachen einer PH wie pulmonal arterielle Hypertonie (PAH) oder chronisch thromboembolische pulmonale Hypertonie (CTEPH) gefahndet werden. Zur Diagnosestellung der PH ist dann letztendlich eine vollständige Rechtsherzkatheter-Untersuchung unabdingbar.
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- 2017
11. [Hemodynamic Definition of Pulmonary Hypertension: Commentary on the Proposed Change by the 6th World Symposium on Pulmonary Hypertension]
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Stephan, Rosenkranz, Gerhard-Paul, Diller, Daniel, Dumitrescu, Ralf, Ewert, H Ardeschir, Ghofrani, Ekkehard, Grünig, Michael, Halank, Matthias, Held, Harald, Kaemmerer, Hans, Klose, Gabor, Kovacs, Stavros, Konstantinides, Irene M, Lang, Tobias J, Lange, Hanno, Leuchte, Eckhard, Mayer, Andrea, Olschewski, Horst, Olschewski, Karen M, Olsson, Christian, Opitz, Ralph T, Schermuly, Werner, Seeger, Heinrike, Wilkens, and Marius M, Hoeper
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Europe ,Hypertension, Pulmonary ,Practice Guidelines as Topic ,Cardiology ,Hemodynamics ,Pulmonary Medicine ,Humans ,Vascular Resistance ,Antihypertensive Agents - Abstract
The ESC/ERS guidelines (published at the end of 2015) and other international recommendations defined pulmonary hypertension (PH) by an invasively measured mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest. At the 6Die Ende 2015 veröffentlichten ESC/ERS-Leitlinien und andere internationale Empfehlungen definierten die pulmonale Hypertonie (PH) bisher durch einen invasiv gemessenen mittleren pulmonal arteriellen Druck (mPAP) ≥ 25 mmHg in Ruhe. Auf dem 6
- Published
- 2019
12. Risikostratifizierung und Verlaufskontrollen bei PAH-Patienten: Empfehlungen der Kölner Konsensus-Konferenz 2016
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Marius M. Hoeper, Michael Halank, Harald Kaemmerer, Silvia Ulrich, Martin Schwaiblmair, Christian M. Kähler, G. Riemekasten, H. ten Freyhaus, Henning Gall, Ralf Ewert, Hanno Leuchte, and University of Zurich
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medicine.medical_specialty ,business.industry ,Consensus conference ,MEDLINE ,610 Medicine & health ,2700 General Medicine ,General Medicine ,030204 cardiovascular system & hematology ,language.human_language ,3. Good health ,Respiratory Medicine ,German ,03 medical and health sciences ,0302 clinical medicine ,Family medicine ,Risk stratification ,language ,Medicine ,030212 general & internal medicine ,10178 Clinic for Pneumology ,business ,Working group ,Pulmonary hemodynamics ,Pediatric cardiology - Abstract
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.
- Published
- 2016
13. Late outcomes after acute pulmonary embolism: rationale and design of FOCUS, a prospective observational multicenter cohort study
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Christian Opitz, Harald Binder, Philipp S. Wild, Martin Faehling, Bianca Zäpf, Hanno Leuchte, Leonard Bruch, Mareike Lankeit, Ekkehard Grünig, Stephan Rosenkranz, Nadine Heydenreich, Hans-Jürgen Seyfarth, Stavros Konstantinides, Rolf Wachter, Felix Gerhardt, Michael Halank, Antonio Pinto, Julia Freise, Ralf Ewert, Claus Neurohr, Matthias Held, F. Joachim Meyer, Eckhard Mayer, Heinrike Wilkens, Stefano Barco, Marius M. Hoeper, and Hossein Ardeschir Ghofrani
- Subjects
Quality of life ,Male ,medicine.medical_specialty ,Pulmonary embolism ,Chronic thromboembolic pulmonary hypertension ,Functional impairment ,Cohort study ,Follow-up ,Aftercare ,030204 cardiovascular system & hematology ,Article ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Prospective Studies ,Intensive care medicine ,Prospective cohort study ,Cause of death ,business.industry ,Sequela ,Hematology ,Guideline ,medicine.disease ,3. Good health ,Survival Rate ,030228 respiratory system ,Acute Disease ,Observational study ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Acute pulmonary embolism (PE) is a frequent cause of death and serious disability. The risk of PE-associated mortality and morbidity extends far beyond the acute phase of the disease. In earlier follow-up studies, as many as 30 % of the patients died during a follow-up period of up to 3 years, and up to 50 % of patients continued to complain of dyspnea and/or poor physical performance 6 months to 3 years after the index event. The most feared ‘late sequela’ of PE is chronic thromboembolic pulmonary hypertension (CTEPH), the true incidence of which remains obscure due to the large margin of error in the rates reported by mostly small, single-center studies. Moreover, the functional and hemodynamic changes corresponding to early, possibly reversible stages of CTEPH, have not been systematically investigated. The ongoing Follow-Up after acute pulmonary embolism (FOCUS) study will prospectively enroll and systematically follow, over a 2-year period and with a standardized comprehensive program of clinical, echocardiographic, functional and laboratory testing, a large multicenter prospective cohort of 1000 unselected patients (all-comers) with acute symptomatic PE. FOCUS will possess adequate power to provide answers to relevant remaining questions regarding the patients’ long-term morbidity and mortality, and the temporal pattern of post-PE abnormalities. It will hopefully provide evidence for future guideline recommendations regarding the selection of patients for long-term follow-up after PE, the modalities which this follow-up should include, and the findings that should be interpreted as indicating progressive functional and hemodynamic post-PE impairment, or the development of CTEPH. Electronic supplementary material The online version of this article (doi:10.1007/s11239-016-1415-7) contains supplementary material, which is available to authorized users.
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- 2016
14. Risk stratification strategy and assessment of disease progression in patients with pulmonary arterial hypertension: Updated Recommendations from the Cologne Consensus Conference 2018
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Silvia Ulrich, Martin Schwaiblmair, Christian M. Kähler, Ralf Ewert, Marius M. Hoeper, Harald Kaemmerer, Gabriela Riemekasten, Henrik ten Freyhaus, Hanno Leuchte, Michael Halank, Henning Gall, University of Zurich, and Leuchte, Hanno H
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medicine.medical_specialty ,Consensus Development Conferences as Topic ,Hypertension, Pulmonary ,Clinical Decision-Making ,610 Medicine & health ,030204 cardiovascular system & hematology ,Risk Assessment ,2705 Cardiology and Cardiovascular Medicine ,German ,03 medical and health sciences ,0302 clinical medicine ,Germany ,medicine ,Humans ,In patient ,Intensive care medicine ,business.industry ,Disease progression ,Consensus conference ,medicine.disease ,Pulmonary hypertension ,language.human_language ,030228 respiratory system ,Risk stratification ,Practice Guidelines as Topic ,language ,Disease Progression ,10178 Clinic for Pneumology ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,Pediatric cardiology - Abstract
In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines and included new evidence, where available, and were last updated in the spring of 2018. This article focusses on the proposed risk stratification and assessment of disease progression in patients with pulmonary arterial hypertension (PAH), covering 3 parts: In part 1, methods and markers that are recommended to assess severity and progression of PAH are discussed and commented. These updated comments incorporate most recent data as well as challenges arising from the variability of phenotypes of PAH patients with increasing cardiopulmonary comorbidities. In part 2, the proposed ESC/ERS risk stratification strategy is discussed, together with a review of the recent validation studies from different European registries. Finally, in part 3, the working group of the Cologne Consensus Conference provides recommendations on how risk assessment may be implemented in routine clinical practice and may serve clinical decision making.
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- 2018
15. Idiopathic Pulmonary Fibrosis Among Young Patients: Challenges in Diagnosis and Management
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Simone Reu, Gabriela Leuschner, Tobias Veit, G. Zimmermann, Felix Ceelen, Friederike Klenner, Florian Stocker, Claus Neurohr, Fredrik Reiter, Alexander Crispin, Jürgen Behr, Julien Dinkel, Nikolaus Kneidinger, and Hanno Leuchte
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Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Time Factors ,Biopsy ,Respiratory System Agents ,Disease ,Comorbidity ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Lung ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Medical record ,Interstitial lung disease ,Clinical course ,Age Factors ,respiratory system ,Middle Aged ,medicine.disease ,Idiopathic Pulmonary Fibrosis ,respiratory tract diseases ,Treatment Outcome ,030228 respiratory system ,Respiratory failure ,Disease Progression ,Female ,business ,Lung Transplantation - Abstract
Idiopathic pulmonary fibrosis (IPF) is considered a disease of older patients, being rare in patients ≤ 50 years. Still, IPF can occur in younger patients, but this particular patient group is not well characterised so far. The aim of this study was to compare the diagnostic certainty, clinical features, comorbidities and survival in young versus older IPF patients. We reviewed our medical records from February 2011 until February 2015, to identify IPF patients, who were then classified as young (≤ 50 years) or older IPF (> 50 years). Radiographic and histological findings, lung function parameters, comorbidities, disease progression and survival were analysed and compared between the two groups. Of 440 patients with interstitial lung disease, 129 patients with IPF were identified, including 30 (23.3%) ≤50 years and 99 (76.7%) > 50 years. There were no differences between age groups in baseline demographics; younger patients were less likely to have a confirmed diagnosis by high-resolution computed tomography (p = 0.014), more likely to require a biopsy (p = 0.08) and less likely to have received antifibrotic therapy (p = 0.006). Despite an overall limited prognosis, younger patients had a significantly better median survival after diagnosis (p = 0.0375), with a significantly higher proportion of older patients dying due to respiratory failure (p = 0.0383). IPF patients under the age of 50 years have similar features and clinical course compared to older IPF patients. These patients should be diagnosed by adopting a multidisciplinary team approach, potentially benefitting from earlier intervention with effective antifibrotic therapy.
- Published
- 2018
16. Targeted therapy of pulmonary arterial hypertension: Updated recommendations from the Cologne Consensus Conference 2018
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H. Ardeschir Ghofrani, Michael Halank, Hans-Joachim Kabitz, Christian Apitz, Ralf Ewert, Harald Kaemmerer, Christian M. Kähler, Ekkehard Grünig, Stephan Rosenkranz, Marius M. Hoeper, Hanno Leuchte, Hans Klose, Oliver Distler, Karen M. Olsson, Silvia Ulrich, University of Zurich, and Hoeper, Marius M
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Endothelin Receptor Antagonists ,medicine.medical_specialty ,Combination therapy ,medicine.medical_treatment ,Consensus Development Conferences as Topic ,Hypertension, Pulmonary ,610 Medicine & health ,030204 cardiovascular system & hematology ,2705 Cardiology and Cardiovascular Medicine ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Drug Delivery Systems ,Germany ,medicine ,Humans ,In patient ,Intensive care medicine ,Adverse effect ,business.industry ,Consensus conference ,10051 Rheumatology Clinic and Institute of Physical Medicine ,Phosphodiesterase 5 Inhibitors ,medicine.disease ,Pulmonary hypertension ,Combined Modality Therapy ,030228 respiratory system ,Practice Guidelines as Topic ,10178 Clinic for Pneumology ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,Pediatric cardiology - Abstract
In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines and included new evidence, where available. The treatment algorithm for PAH was modified based on the observation that there are now many patients diagnosed with IPAH who are at an advanced age and have significant cardiopulmonary comorbidities. For patients newly diagnosed with classic forms of PAH, i.e. younger patients without significant cardiopulmonary comorbidities, the consensus-based recommendation was to use initial combination therapy as the standard approach. The use of monotherapies was no longer considered appropriate in such patients. The choice of treatment strategies should be based on the risk assessment as proposed in the European guidelines. In patients presenting with a low or intermediate risk, oral combination therapy with endothelin receptor antagonists and phosphodiesterase-5 inhibitors or soluble guanylate cyclase stimulators, respectively, should be used. In high-risk patients, triple combination therapy including a subcutaneous or intravenous prostacyclin analogue should be considered. For patients who suffer from PAH and significant cardiopulmonary comorbidities, initial monotherapy is recommended and the use of combination therapies should be considered on an individual basis. The latter recommendations are based on the scarcity of evidence supporting the use of combination therapy and the higher risk of drug-related adverse events in such patients.
- Published
- 2018
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17. Augmentation of the effects of vasoactive intestinal peptide aerosol on pulmonary hypertension via coapplication of a neutral endopeptidase 24.11 inhibitor
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Juergen Behr, Christoph Prechtl, Shani Haziraj, Hanno Leuchte, Dorian Bevec, Jens Callegari, and Tobias Meis
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Pulmonary and Respiratory Medicine ,Thiorphan ,medicine.medical_specialty ,Physiology ,Thromboxane ,Hypertension, Pulmonary ,Vasoactive intestinal peptide ,Blood Pressure ,chemistry.chemical_compound ,Physiology (medical) ,medicine.artery ,Internal medicine ,Hypoxic pulmonary vasoconstriction ,Administration, Inhalation ,medicine ,Animals ,Protease Inhibitors ,Lung ,Inhalation ,business.industry ,Cell Biology ,medicine.disease ,Pulmonary hypertension ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Vasoconstriction ,Pulmonary artery ,Neprilysin ,Rabbits ,medicine.symptom ,business ,hormones, hormone substitutes, and hormone antagonists ,Vasoactive Intestinal Peptide - Abstract
Rationale: A deficiency of the pulmonary vasodilative vasoactive intestinal peptide (VIP) has been suggested to be involved in the pathophysiology of pulmonary hypertension (PH). Supplementation of VIP as an aerosol is hampered by the fact that it is rapidly inactivated by neutral endopeptidases (NEP) located on the lung surface. Hypothesis: Co-application of thiorphan, a NEP 24.11 inhibitor, could augment the biological effects of inhaled VIP alone. Methods: A stable pulmonary vasoconstriction with a 3-fold increase of pulmonary artery pressure was established by application the thromboxane mimetic U46619 in the isolated rabbit lung model. VIP and thiorphan were either applied i.v. or as an aerosol. Results: VIP caused a significant pulmonary vasodilation either during i.v. application or inhalation. These effects were of short duration. Thiorphan application had no effects on pulmonary vasoconstriction per se, but significantly augmented the effects of VIP aerosol. Thiorphan not only augmented the maximum hemodynamic effects of VIP aerosol, but also led to a significant prolongation of these effects. Conclusion: VIP causes pulmonary vasodilation in a model of acute experimental PH. The hemodynamic effects of VIP aerosol can be significantly augmented via co-application of a NEP inhibitor.
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- 2015
18. Riociguat: Stimulation der löslichen Guanylatzyklase
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Matthias Held, Hanno Leuchte, H Wilkens, Hossein Ardeschir Ghofrani, Ekkehard Grünig, Marius M. Hoeper, Ralph T. Schermuly, Hans Klose, Michael Halank, Stephan Rosenkranz, Juergen Behr, and Ralf Ewert
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Pulmonary and Respiratory Medicine ,Pulmonary Metabolism ,business.industry ,Treatment outcome ,Pharmacology ,Riociguat ,Chronic disease ,Medicine ,Chronic thromboembolic pulmonary hypertension ,business ,Mode of action ,Soluble guanylyl cyclase ,medicine.drug ,Guanylate cyclase - Abstract
Riociguat ist der erste klinisch verfugbare Vertreter der Stimulatoren der loslichen Guanylatzyklase (sGC), einer neuartigen Substanzgruppe. Die primare Zulassungsindikation erhielt Riociguat fur die pulmonal-arterielle Hypertonie (PAH) und fur die Behandlung der nicht operablen bzw. postoperativ wiederkehrenden/persistierenden chronisch thomboembolischen pulmonalen Hypertonie (CTEPH). Daruber hinaus besteht ein Studienprogramm in weiteren Indikationsgebieten. Der nachfolgende Artikel beschreibt den Wirkmechanismus und die bisher verfugbaren klinischen Daten von Riociguat. Zudem ziehen die Autoren aus den vorliegenden Daten, der Zulassungs- und der Kostensituation ein Fazit fur die Integration von Riociguat in den bisherigen Therapiealgorithmus der PAH und CTEPH.
- Published
- 2015
19. RISE-IIP: Riociguat for the treatment of pulmonary hypertension associated with idiopathic interstitial pneumonia
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Silvia Ulrich, Mia Yao, Sukrut Shah, Tamera J. Corte, Stephen Malcolm, Wim A. Wuyts, Anne Keogh, Fernando J. Martinez, Harold R. Collard, Athol U. Wells, Juergen Behr, Hanno Leuchte, Nesrin Mogulkoc, Marius M. Hoeper, Steven D. Nathan, and Vincent Cottin
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030213 general clinical medicine ,medicine.medical_specialty ,business.industry ,medicine.disease ,Placebo ,Riociguat ,Pulmonary hypertension ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,030228 respiratory system ,Internal medicine ,medicine.artery ,Pulmonary artery ,Clinical endpoint ,medicine ,Cardiology ,Functional ability ,business ,Idiopathic interstitial pneumonia ,medicine.drug - Abstract
Pulmonary hypertension (PH) complicating idiopathic interstitial pneumonias (IIPs) is associated with impaired functional ability and poor outcomes. Whether treating PH in IIP is beneficial remains unknown. RISE-IIP (NCT02138825) was a randomised, placebo (PBO)-controlled study to evaluate the efficacy and safety of riociguat in patients with IIP, FVC ≥45% predicted and mean pulmonary artery pressure ≥25 mmHg. Patients were randomised to riociguat up to 2.5 mg tid or PBO for 26 weeks followed by an open-label extension where all patients received riociguat. The primary endpoint was change from baseline to week 26 in 6-minute walk distance (6MWD). Secondary endpoints included clinical worsening (all-cause mortality, hospitalisation due to worsening cardiopulmonary status, 15% decrease in 6MWD or worsening of WHO FC). Of 147 randomised patients, 73 received riociguat and 74 PBO. The study was stopped early (mean treatment duration 121±66 days) at the recommendation of the Data Monitoring Committee due to increased SAEs (37% riociguat vs 23% PBO in the blinded phase) and increased mortality in riociguat patients. There were 11 deaths in the blinded phase (8 riociguat, 3 PBO), and 9 in the extension (1 former riociguat, 8 former PBO). Riociguat did not improve 6MWD vs PBO at 26 week (least squares mean difference +21 m; 95% CI –9 to +52 m). There was no difference in proportion of subjects with clinical worsening: 47% riociguat vs 49% PBO. In patients with PH-IIP, riociguat was associated with increased SAEs and mortality, and an unfavourable risk:benefit ratio. The current study did not reveal a potential aetiology for the observed mortality effect.
- Published
- 2017
20. The safety and pharmacokinetics of rapid iloprost aerosol delivery via the BREELIB nebulizer in pulmonary arterial hypertension
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Bernhard Müllinger, Hans Klose, Werner Seeger, Matthias Held, Horst Olschewski, Hanno Leuchte, Lueder Fels, Hossein Ardeschir Ghofrani, Tobias Gessler, Dawn Ren, Beate Rohde, Marcus-Hillert Schultze-Mosgau, Stephan Rosenkranz, Andreas Kaiser, and Na Li
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Pulmonary and Respiratory Medicine ,prostacyclin analog ,Inhalation ,business.industry ,inhalation time ,030204 cardiovascular system & hematology ,treatment adherence ,03 medical and health sciences ,Nebulizer ,0302 clinical medicine ,Mean blood pressure ,030228 respiratory system ,Tolerability ,Pharmacokinetics ,Anesthesia ,Heart rate ,medicine ,Adverse effect ,business ,Research Articles ,Iloprost ,medicine.drug ,patient convenience - Abstract
The BREELIB nebulizer was developed for iloprost to reduce inhalation times for patients with pulmonary arterial hypertension (PAH). This multicenter, randomized, unblinded, four-part study compared inhalation time, pharmacokinetics, and acute tolerability of iloprost 5 µg at mouthpiece delivered via BREELIB versus the standard I-Neb nebulizer in 27 patients with PAH. The primary safety outcome was the proportion of patients with a maximum increase in heart rate (HR) ≥ 25% and/or a maximum decrease in systolic blood pressure ≥ 20% within 30 min after inhalation. Other safety outcomes included systolic, diastolic, and mean blood pressure, HR, oxygen saturation, and adverse events (AEs). Median inhalation times were considerably shorter with BREELIB versus I-Neb (2.6 versus 10.9 min; n = 24). Maximum iloprost plasma concentration and systemic exposure (area under the plasma concentration-time curve) were 77% and 42% higher, respectively, with BREELIB versus I-Neb. Five patients experienced a maximum systolic blood pressure decrease ≥ 20%, four with BREELIB (one mildly and transiently symptomatic), and one with I-Neb; none required medical intervention. AEs reported during the study were consistent with the known safety profile of iloprost. The BREELIB nebulizer offers reduced inhalation time, good tolerability, and may improve iloprost aerosol therapy convenience and thus compliance for patients with PAH.
- Published
- 2017
21. Haemodynamic changes in pulmonary hypertension in patients with interstitial lung disease treated with PDE-5 inhibitors
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P Huppmann, Juergen Behr, Tobias Meis, Claus Neurohr, Werner von Wulffen, F. Ihle, G. Zimmermann, Hanno Leuchte, Amanda Tufman, and J. Geiseler
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Sildenafil ,business.industry ,Interstitial lung disease ,respiratory system ,medicine.disease ,Pulmonary hypertension ,Tadalafil ,respiratory tract diseases ,chemistry.chemical_compound ,Idiopathic pulmonary fibrosis ,chemistry ,Internal medicine ,medicine.artery ,Pulmonary fibrosis ,Pulmonary artery ,medicine ,Cardiology ,business ,Pulmonary wedge pressure ,medicine.drug - Abstract
Background and objective Interstitial lung diseases (ILD) are often associated with pulmonary hypertension (PH). This study aimed to evaluate the therapeutic benefit of phosphodiesterase-5 (PDE-5) inhibitors in pulmonary hypertension secondary to ILD. Methods Patients with ILD and PH were treated with sildenafil or tadalafil. Right heart catheterization was performed before and after a minimum of 3-month treatment. In addition, lung function, 6-min walk distance (6MWD) and plasma brain natriuretic peptide (BNP) concentration were assessed. Results Ten ILD patients (three female, mean age 64.4 ± 9.0 years, six with idiopathic pulmonary fibrosis (IPF), four with hypersensitivity pneumonitis, (HP)) with significant precapillary PH (mean pulmonary artery pressure (PAPm) ≥ 25 mmHg, pulmonary vascular resistance (PVR) > 280 dyn*s*cm−5; pulmonary artery wedge pressure (PAWPm) ≤ 15 mmHg) were treated with either sildenafil (n = 5) or tadalafil (n = 5). Pulmonary haemodynamics were severely impaired at baseline (PAPm 42.9 ± 5.4 mmHg; cardiac index (CI) 2.7 ± 0.6 L/min/m2; PVR 519 ± 131 dyn × sec × cm−5). After mean follow-up of 6.9 ± 5.8 months an increase in CI (2.9 ± 0.7 L/min/m2, P = 0.04) and a decrease in PVR (403 ± 190 dyn × sec × cm−5, P = 0.03) were observed. 6MWD and BNP did not change significantly. Conclusions Our data suggest that treatment with PDE-5 inhibitors improves pulmonary haemodynamic patients with PH secondary to ILD.
- Published
- 2014
22. Gezielte Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensuskonferenz 2016
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Christian Apitz, M Halank, Harald Kaemmerer, Silvia Ulrich, Oliver Distler, Stephan Rosenkranz, Ekkehard Grünig, K Olsson, Hans Klose, R Ewert, Marius M. Hoeper, Hossein Ardeschir Ghofrani, Hans-Joachim Kabitz, Christian M. Kähler, Hanno Leuchte, and University of Zurich
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Consensus conference ,10051 Rheumatology Clinic and Institute of Physical Medicine ,610 Medicine & health ,General Medicine ,2700 General Medicine ,030204 cardiovascular system & hematology ,language.human_language ,Targeted therapy ,Respiratory Medicine ,German ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Family medicine ,language ,medicine ,10178 Clinic for Pneumology ,Working group ,business ,Pediatric cardiology - Abstract
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.
- Published
- 2016
23. Residuelle pulmonal vasodilative Reserve als prognostischer Marker der idiopatischen pulmonalarteriellen Hypertonie
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Claus Neurohr, Carlos Baezner, R. Baumgartner, Hanno Leuchte, and Juergen Behr
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Pulmonary and Respiratory Medicine - Published
- 2016
24. Augmentation der durch VIP vermittelten pulmonalen Vasodilatation durch die Ko-Applikation von Thiorphan, einem Inhibitor der neutralen Endopeptidase 24.11
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Tobias Meis, Juergen Behr, Dorian Bevec, C Prechtl, J Callegari, and Hanno Leuchte
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Pulmonary and Respiratory Medicine - Published
- 2016
25. Acute Hemodynamic Responses to Supplemental Oxygen and Their Prognostic Implications in Pulmonary Hypertension
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Jürgen Behr, Hanno Leuchte, R. Baumgartner, Carlos Baezner, Claus Neurohr, and Philipp Mernitz
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Cardiac Catheterization ,Pulmonary Circulation ,Cardiac output ,Haemodynamic response ,Hypertension, Pulmonary ,Hemodynamics ,Oxygen Consumption ,Heart rate ,medicine ,Humans ,Respiratory system ,Hypoxia ,Lung ,Monitoring, Physiologic ,business.industry ,Oxygen Inhalation Therapy ,Middle Aged ,Hypoxia (medical) ,Prognosis ,medicine.disease ,Pulmonary hypertension ,Oxygen ,Treatment Outcome ,medicine.anatomical_structure ,Anesthesia ,Vascular resistance ,Female ,Vascular Resistance ,medicine.symptom ,business - Abstract
Background: Pulmonary hypertension (PH) of various causes leads to a poor prognosis. Pulmonary vasoreactivity testing during right heart catheterization (RHC) has prognostic and therapeutic consequences. Objective: To characterize the acute hemodynamic response to short-term oxygen supplementation (SHOT) in adult PH patients and its impact on prognosis. Methods: After a stable baseline period, 104 patients with PH [pulmonary arterial hypertension (PAH; n = 56), chronic thromboembolic (PH; n = 22) or respiratory diseases (PH; n = 26)], who were mainly therapy-naïve (86.5%) (mean pO2 64.5 ± 1.2 mm Hg), received a standardized SHOT during RHC and hemodynamic response was assessed for its prognostic potential. Results: SHOT significantly reduced heart rate (HR: 78.9 ± 1.5 to 74 ± 1.5 beats/min), cardiac output (4 ± 0.1 to 3.8 ± 0.1 l/min), pulmonary arterial pressure (46.4 ± 1.3 to 42.3 ± 1.3 mm Hg) and pulmonary vascular resistance (10.1 ± 0.5 to 9.6 ± 0.5 Wood units; all p < 0.001) compared to baseline. The magnitude of this effect varied between the different PH groups. During a median follow-up of 25.1 months (range: 0.2-73.3 months), HR Conclusions: SHOT leads to characteristic hemodynamic responses across different forms of PH. The preserved capability to acutely respond to SHOT with HR reduction is of prognostic significance in patients with non PAH PH.
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- 2012
26. Treat-to-target approach in pulmonary arterial hypertension: a consensus-based proposal
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Olivier Sitbon, Wendy Gin-Sing, David G. Kiely, Pilar Escribano, Kjell Jansson, Hanno Leuchte, Adolfo Baloira Villar, Fabrice Bauer, Björn Ekmehag, Alessandra Manes, and Stephan Rosenkranz
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Consensus ,medicine.drug_class ,Hypertension, Pulmonary ,Cardiac index ,MEDLINE ,Pulmonary Artery ,World health ,Predictive Value of Tests ,Risk Factors ,Correspondence ,medicine ,Natriuretic peptide ,Humans ,Arterial Pressure ,Familial Primary Pulmonary Hypertension ,Intensive care medicine ,Antihypertensive Agents ,lcsh:RC705-779 ,business.industry ,Treat to target ,lcsh:Diseases of the respiratory system ,medicine.disease ,Pulmonary hypertension ,Checklist ,Review article ,Treatment Outcome ,Predictive value of tests ,Practice Guidelines as Topic ,Guideline Adherence ,business - Abstract
To the Editor: Goal-oriented therapy, also known as treat-to-target therapy, is recommended in the European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension [1, 2]. This approach, first described by Hoeper et al . [3], has emerged, alongside early detection, as a central aspect of managing pulmonary arterial hypertension (PAH). Goal-oriented therapy is proactive as it defines treatment goals ahead of time and proposes to alter the treatment strategy if those goals are not met. In a review article on goal-oriented therapy in PAH by Sitbon and Galie [4], the authors noted that existing treatment goals are mainly based on parameters with prognostic value at baseline and highlighted the need for additional data to identify goals that have prognostic relevance during treatment. Subsequently, a single-centre study in 109 patients with idiopathic PAH has provided evidence to support the prognostic importance of achieving certain goals during therapy [5]. In this study, the following parameters were individually associated with improved prognosis when assessed at the first follow-up visit (3–12 months after initiation of PAH-specific therapy), supporting their use as treatment goals: 1) improvement to, or maintenance of, New York Heart Association/World Health Organization functional class (FC) I or II; 2) cardiac index ≥2.5 L·min−1·m−2; 3) mixed venous oxygen saturation ≥65%; or 4) N-terminal pro-brain natriuretic peptide (BNP) levels …
- Published
- 2012
27. Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial
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Irmingard Gebert, Andreas Günther, Heinrike Wilkens, Marius M. Hoeper, Jürgen Behr, Michael Halank, Hanno Leuchte, and Gerrit Weimann
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Cardiac output ,medicine.medical_specialty ,Hypertension, Pulmonary ,Administration, Oral ,Receptors, Cytoplasmic and Nuclear ,Pilot Projects ,Riociguat ,Soluble Guanylyl Cyclase ,Internal medicine ,medicine.artery ,Humans ,Medicine ,Aged ,Aged, 80 and over ,business.industry ,Hemodynamics ,Interstitial lung disease ,Middle Aged ,medicine.disease ,Interim analysis ,Pulmonary hypertension ,Surgery ,Oxygen ,Pyrimidines ,Treatment Outcome ,medicine.anatomical_structure ,Tolerability ,Guanylate Cyclase ,Pulmonary artery ,Cardiology ,Vascular resistance ,Pyrazoles ,Female ,Lung Diseases, Interstitial ,business ,medicine.drug - Abstract
We assessed the safety, tolerability and preliminary efficacy of riociguat, a soluble guanylate cyclase stimulator, in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). In this open-label, uncontrolled pilot trial, patients received oral riociguat (1.0-2.5 mg three times daily) for 12 weeks (n=22), followed by an ongoing long-term extension (interim analysis at 12 months) in those eligible (n=15). Primary end-points were safety and tolerability. Secondary end-points included haemodynamic changes and 6-min walk distance (6MWD). Overall, 104 adverse events were reported, of which 25 were serious; eight of the latter were considered drug-related. After 12 weeks of therapy, mean cardiac output increased (4.4 ± 1.5 L · min(-1) to 5.5 ± 1.8 L · min(-1)), pulmonary vascular resistance (PVR) decreased (648 ± 207 dyn · s(-1) · cm(-5) to 528 ± 181 dyn · s(-1) · cm(-5)) and mean pulmonary artery pressure (mPAP) remained unchanged compared with baseline. Arterial oxygen saturation decreased but mixed-venous oxygen saturation slightly increased. The 6MWD increased from 325 ± 96 m at baseline to 351 ± 111 m after 12 weeks. Riociguat was well tolerated by most patients and improved cardiac output and PVR, but not mPAP. Further studies are necessary to evaluate the safety and efficacy of riociguat in patients with PH-ILD.
- Published
- 2012
28. Safety and efficacy of exercise training in various forms of pulmonary hypertension
- Author
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Hans-Jürgen Seyfarth, Hans Klose, Gerd Staehler, Christine Fischer, Christian Opitz, Hossein Ardeschir Ghofrani, Mona Lichtblau, Nicola Ehlken, Stephan Sorichter, Stephan Rosenkranz, Gabriele Karger, Ekkehard Grünig, Andreas Meyer, Michael Halank, Hanno Leuchte, Rudolf Speich, Frank Reichenberger, Heinrike Wilkens, and Christian Nagel
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,Hypertension, Pulmonary ,Oxygen pulse ,Walking ,Young Adult ,Oxygen Consumption ,Quality of life ,Internal medicine ,medicine.artery ,Heart rate ,medicine ,Humans ,Prospective Studies ,Adverse effect ,Prospective cohort study ,Aged ,Aged, 80 and over ,Presyncope ,business.industry ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Exercise Therapy ,Treatment Outcome ,Pulmonary artery ,Quality of Life ,Cardiology ,Physical therapy ,Female ,business - Abstract
The objective of this prospective study was to assess safety and efficacy of exercise training in a large cohort of patients with different forms and World Health Organization (WHO) functional classes of chronic pulmonary hypertension (PH). 183 patients with PH (pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH due to respiratory or left heart diseases received exercise training in hospital for 3 weeks and continued at home. Adverse events have been monitored during the in-hospital training programme. Efficacy parameters were evaluated at baseline, and after 3 and 15 weeks. After 3 and 15 weeks, patients significantly improved the distance walked in 6 min (6MWD) compared to baseline, scores of quality of life, WHO functional class, peak oxygen consumption, oxygen pulse, heart rate and systolic pulmonary artery pressure at rest and maximal workload. The improvement in 6MWD was similar in patients with different PH forms and functional classes. Even in severely affected patients (WHO functional class IV), exercise training was highly effective. Adverse events, such as respiratory infections, syncope or presyncope, occurred in 13% of patients. Exercise training in PH is an effective but not a completely harmless add-on therapy, even in severely diseased patients, and should be closely monitored.
- Published
- 2012
29. Non-invasive diagnosis of pulmonary hypertension: ESC/ERS Guidelines with Updated Commentary of the Cologne Consensus Conference 2011
- Author
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Gabor G. Kovacs, Joachim F. Meyer, Gabriela Riemekasten, Michael Bell, Stephan Sorichter, Michael Dandel, Jörg Winkler, Martin Claussen, Matthias Gorenflo, Joachim Saur, A Barner, Daniel Dumitrescu, S Holt, Catherine Seck, Martin Schwaiblmair, Ekkehard Grünig, Hanno Leuchte, Stefan Pabst, Lutz Sinn, and Sebastian Ley
- Subjects
medicine.medical_specialty ,Pediatrics ,Hypertension, Pulmonary ,MEDLINE ,German ,Electrocardiography ,Humans ,Medicine ,Evidence-Based Medicine ,business.industry ,Non invasive ,Consensus conference ,Evidence-based medicine ,medicine.disease ,Pulmonary hypertension ,language.human_language ,Respiratory Function Tests ,Echocardiography ,Family medicine ,Practice Guidelines as Topic ,Exercise Test ,language ,Cardiology and Cardiovascular Medicine ,Working group ,business ,Biomarkers ,Pediatric cardiology - Abstract
The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. 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 2010, 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 non-invasive diagnosis of pulmonary hypertension. This manuscript describes in detail the results and recommendations of the working group which were last updated in October 2011.
- Published
- 2011
30. Usefulness of Exhaled Nitric Oxide to Guide Risk Stratification for Bronchiolitis Obliterans Syndrome After Lung Transplantation
- Author
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Hanno Leuchte, Lorenz Frey, RA Hatz, Hauke Winter, Carlos Baezner, Iris Bittmann, G. Zimmermann, Claus Neurohr, F. Ihle, Juergen Behr, W. von Wulffen, S. Leuschner, P Huppmann, Peter Ueberfuhr, and Tobias Meis
- Subjects
Male ,Risk ,medicine.medical_specialty ,medicine.medical_treatment ,Bronchiolitis obliterans ,Nitric Oxide ,Gastroenterology ,New onset ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Lung transplantation ,Pharmacology (medical) ,Prospective Studies ,Bronchiolitis Obliterans ,Transplantation ,business.industry ,Middle Aged ,respiratory system ,medicine.disease ,Predictive value ,humanities ,respiratory tract diseases ,Surgery ,Exhalation ,Risk stratification ,Exhaled nitric oxide ,Female ,business ,Follow-Up Studies ,Lung Transplantation - Abstract
The aim of this study was to assess fractional exhaled nitric oxide (FeNO) for the early diagnosis of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). 611 FeNO measurements in 166 consecutive patients were classified depending on BOS stage at the time of assessment and course during minimum follow-up of 3 months: (1) stable non-BOS, (2) unstable non-BOS, (3) stable BOS and (4) unstable BOS. Unstable course was defined as new onset of BOS≥1 or progression of BOS. FeNO before unstable course was significantly increased in comparison to their stable counterparts (non-BOS: 28.9 ± 1.2 ppb, n = 40 vs. 16.4 ± 0.8 ppb, n = 131 and BOS: 32.5 ± 1.3 ppb, n = 35 vs. 15.3 ± 0.8 ppb, n = 26; p = 0.01 each). Average time from FeNO reading to onset of deterioration was 117 ± 9 days in non-BOS and 136 ± 9 days in BOS patients. The positive and negative predictive value of FeNO >20 ppb for BOS was 69.0% and 96.9%, respectively. Serial measurements demonstrated significantly lower mean individual variation in stable recipients as compared to stable patients switching to unstable course (3.2 ± 0.3 ppb vs. 12.7 ± 1.4 ppb, p = 0.02). In particular, the excellent negative predictive value of persistently low FeNO readings for future BOS make FeNO assessments a useful tool for continuous risk stratification after LTX.
- Published
- 2011
31. Nicht-invasive Diagnostik der pulmonalen Hypertonie
- Author
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Joachim F. Meyer, Daniel Dumitrescu, Michael Dandel, Martin Claussen, Ekkehard Grünig, Joachim Saur, Martin Schwaiblmair, J. Winkler, G. Riemekasten, Sebastian Ley, M Bell, Hanno Leuchte, Stefan Pabst, Matthias Gorenflo, L Sinn, Catherine Seck, Stephan Sorichter, A Barner, Gabor Kovacs, and S Holt
- Subjects
Gynecology ,Respiratory Medicine ,medicine.medical_specialty ,Pediatrics ,business.industry ,Consensus conference ,Medicine ,General Medicine ,business ,Pediatric cardiology - Abstract
Die 2009 veroffentliche Europaischen Leitlinien zur Diagnostik und Therapie der pulmonalen Hypertonie sind nunmehr auch in Deutschland gultig. Die Leitlinien befassen sich eingehend mit der Diagnostik der pulmonalen Hypertonie. Fur die praktische Umsetzung der Europaischen Leitlinien in Deutschland sind jedoch zahlreiche spezifische Gesichtspunkte und neue Daten bedeutsam, die eine ausfuhrliche Kommentierung der Leitlinien und in einigen Punkten eine Aktualisierung notwendig machen. Im Juni 2010 fand in Koln eine Konsensuskonferenz statt, die von den Arbeitsgruppen PH der Deutschen Gesellschaften fur Kardiologie (DGK), Pneumologie (DGP) und Padiatrische Kardiologie (DGPK) organisiert wurde. Die Konferenz befasste sich mit der Umsetzung der Europaischen Leitlinien in Deutschland. Dazu wurden verschiedene Arbeitsgruppen eingesetzt, von denen sich eine gezielt der nicht-invasiven Diagnostik der pulmonalen Hypertonie widmete. Die Ergebnisse und Beschlusse dieser Arbeitsgruppe werden in dem vorliegenden Manuskript detailliert beschrieben. The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. 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 y appears necessary. In June 2010, 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 non-invasive diagnosis of PH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.
- Published
- 2010
32. Pulmonale Hypertonie: invasive Diagnostik
- Author
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R Blindt, Jochen Weil, R Ewert, Christian Opitz, Leonhard Bruch, H Tiede, Stephan Rosenkranz, K Peters, Christian Nagel, Dietmar Schranz, Mona Lichtblau, Mathias M. Borst, Dirk Skowasch, F Blumberg, and Hanno Leuchte
- Subjects
Right heart catheterization ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,General Medicine ,medicine.disease ,business ,Pulmonary hypertension - Published
- 2010
33. Preserved pulmonary vasodilative properties of aerosolized brain natriuretic peptide
- Author
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Shani Haziraj, Hanno Leuchte, Jens Michalek, Vera Cavalli, Tobias Meis, Jürgen Behr, Dorian Bevec, and Oezcan Soenmez
- Subjects
Pulmonary and Respiratory Medicine ,Pulmonary Circulation ,medicine.medical_specialty ,medicine.drug_class ,Blood Pressure ,Vasodilation ,Buffers ,In Vitro Techniques ,Thromboxane A2 ,chemistry.chemical_compound ,Internal medicine ,Hypoxic pulmonary vasoconstriction ,Natriuretic Peptide, Brain ,Natriuretic peptide ,Animals ,Vasoconstrictor Agents ,Medicine ,Pharmacology (medical) ,Cyclic GMP ,Cyclic guanosine monophosphate ,Aerosols ,Dose-Response Relationship, Drug ,Endothelin-1 ,business.industry ,Biochemistry (medical) ,medicine.disease ,Brain natriuretic peptide ,Pulmonary hypertension ,Endocrinology ,chemistry ,Vasoconstriction ,15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ,cardiovascular system ,Rabbits ,medicine.symptom ,business - Abstract
Introduction Inhalation of vasoactive substances is an effective treatment of pulmonary hypertension. The B-type natriuretic peptide (BNP) leads to relaxation of smooth muscle cells, caused by an increased formation of cyclic guanosine monophosphate (cGMP). The biologic activity of BNP using an inhalative approach has not been addressed. Methods In order to assess the vasorelaxing capacity of exogenous BNP in the isolated ventilated and buffer perfused rabbit lung model, a stable pulmonary vasoconstriction was established by either the application of endothelin-1 or the thromboxane A2 mimetic U46619. This was followed by an intravascular or aerosol application of BNP. CGMP was measured in the recirculating buffer fluid using a radioimmunoassay technique. Results During a stable plateau of U46619 induced pulmonary vasoconstriction (mean pulmonary artery pressure, PAP 25.5 ± 0.23 mmHg), the intravascular administration of BNP induced a rapid vasodilation (mean PAP 18.13 ± 0.95 mmHg, p
- Published
- 2009
34. Inhalation of vasoactive intestinal peptide in pulmonary hypertension
- Author
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Juergen Behr, Dorian Bevec, R. Baumgartner, Claus Neurohr, G. Bacher, Carlos Baezner, and Hanno Leuchte
- Subjects
Adult ,Lung Diseases ,Male ,Pulmonary and Respiratory Medicine ,Heart Ventricles ,Hypertension, Pulmonary ,Blood Pressure ,medicine ,Humans ,Phentolamine ,Aged ,Aerosols ,Heart Failure ,Lung ,Inhalation ,business.industry ,Respiratory disease ,Stroke volume ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Oxygen ,Drug Combinations ,medicine.anatomical_structure ,Blood pressure ,Anesthesia ,Heart failure ,Vascular resistance ,Female ,business ,Vasoactive Intestinal Peptide - Abstract
Pulmonary hypertension (PH) leads to an increased right ventricular workload, cardiac failure and death. In idiopathic pulmonary arterial hypertension (PAH) the vasodilating vasoactive intestinal peptide (aviptadil) is deficient. The aim of the present study was to test the acute effects on haemodynamics and blood gases, and the safety, of a single dose of inhaled aviptadil in chronic PH. A total of 20 patients with PH (PAH in nine, PH in lung disease in eight and chronic thromboembolic PH in three) inhaled a single 100-microg dose of aviptadil during right-heart catheterisation. Haemodynamics and blood gases were measured. Aviptadil aerosol caused a small and temporary but significant selective pulmonary vasodilation, an improved stroke volume and mixed venous oxygen saturation. Overall, six patients experienced a pulmonary vascular resistance reduction of >20%. In patients with significant lung disease, aviptadil tended to improve oxygenation. The pulmonary vasodilating effect of aviptadil aerosol was modest and short-lived, did not cause any side-effects and led to a reduced workload of the right ventricle without affecting systemic blood pressure. Aviptadil inhalation tended to improve oxygenation in patients with significant lung disease. Further studies are needed to evaluate the full therapeutic potential of aviptadil aerosol, including higher doses and chronic treatment.
- Published
- 2008
35. Self-Report Daily Life Activity as a Prognostic Marker of Idiopathic Pulmonary Fibrosis
- Author
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Werner von Wulffen, R. Baumgartner, Juergen Behr, Claus Neurohr, Hanno Leuchte, Philip Mernitz, and Carlos Baezner
- Subjects
Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Pathology ,Gastroenterology ,Severity of Illness Index ,Life activity ,Idiopathic pulmonary fibrosis ,Internal medicine ,Germany ,Severity of illness ,Activities of Daily Living ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Self report ,Idiopathic interstitial pneumonia ,business.industry ,Disease progression ,food and beverages ,respiratory system ,Middle Aged ,medicine.disease ,Prognosis ,Idiopathic Pulmonary Fibrosis ,respiratory tract diseases ,Respiratory Function Tests ,Disease Progression ,Exercise Test ,Female ,Self Report ,business ,Progressive disease ,Follow-Up Studies - Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease, leading to substantial physical impairment. The distance walked in 6 min (6MWD) is a measure of exercise tolerance and is of prognostic relevance in IPF. While 6MWD is a punctual measurement which may not be representative, self-reported daily life activity may represent the patients' functional capacity more globally even in less severe affected patients. Objectives: We evaluated and characterized a simple classification system based on the patients' self-reported daily activity and analyzed if this would add significantly to the prognostic information of the 6MWD alone in IPF patients. Methods: Daily life activity was assessed in IPF (n = 156) patients with standardized questions and categorized in activity classes (AC I-IV), comprising the less severe impaired in AC I and II. The 6MWD was also assessed. Results: ACs were related to the lung functional impairment and inversely correlated to the 6MWD. Thirty-two patients were in AC I/II, 98 in AC III and 26 patients in AC IV. Thirty-seven (23.7%) patients died during a median follow-up of 14.9 months, comprising 1 patient in AC I/II. In addition, a 6MWD 470 m identified a subgroup of patients with favorable outcome. Conclusions: AC is a novel scoring system which can easily be obtained and correlates with lung functional and physical impairments as well as mortality. Moreover, AC adds prognostic information to the 6MWD.
- Published
- 2015
36. Residual pulmonary vasodilative reserve predicts outcome in idiopathic pulmonary hypertension
- Author
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Claus Neurohr, Carlos Baezner, Hanno Leuchte, R. Baumgartner, Juergen Behr, and Olaf Muehling
- Subjects
Male ,medicine.medical_specialty ,Cardiac Catheterization ,medicine.medical_treatment ,Idiopathic Pulmonary Hypertension ,Hypertension, Pulmonary ,Vasodilator Agents ,Vasodilation ,Disease ,medicine.artery ,Internal medicine ,medicine ,Humans ,Iloprost ,Cardiac catheterization ,Inhalation ,business.industry ,Middle Aged ,Calcium Channel Blockers ,Prognosis ,Catheter ,Pulmonary artery ,Cardiology ,Female ,Vascular Resistance ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Idiopathic pulmonary arterial hypertension (IPAH) remains a devastating and incurable, albeit treatable condition. Treatment response is not uniform and parameters that help to anticipate a rather benign or a malignant course of the disease are warranted. Acute pulmonary vasoreactivity testing during right heart catheterisation is recommended to identify a minority of patients with IPAH with sustained response to calcium channel blocker therapy. This study aimed to evaluate the prognostic significance of a residual pulmonary vasodilative reserve in patients with IPAH not meeting current vasoresponder criteria.Observational right heart catheter study in 66 (n=66) patients with IPAH not meeting current vasoresponse criteria. Pulmonary vasodilative reserve was assessed by inhalation of 5 µg iloprost-aerosol.Sixty-six (n=66) of 72 (n=72) patients with IPAH did not meet current definition criteria assessed during vasodilator testing to assess pulmonary vasodilatory reserve. In those, iloprost-aerosol caused a reduction of mean pulmonary artery pressure (Δ pulmonary artery pressure-11.4%; p0.001) and increased cardiac output (Δ cardiac output +16.7%; p0.001), resulting in a reduction of pulmonary vascular resistance (Δ pulmonary vascular resistance-25%; p0.001). The magnitude of this response was pronounced in surviving patients. A pulmonary vascular resistance reduction of ≥30% turned out to predict outcome in patients with IPAH.Residual pulmonary vasodilative reserve during acute vasodilator testing is of prognostic relevance in patients with IPAH not meeting current definitions of acute vasoreactivity. Therefore vasoreactivity testing holds more information than currently used.
- Published
- 2015
37. Brain Natriuretic Peptide Is a Prognostic Parameter in Chronic Lung Disease
- Author
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Hanno Leuchte, R. Baumgartner, Michael Vogeser, Juergen Behr, Michael Trautnitz, Claus Neurohr, and Michal El Nounou
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Spirometry ,Cardiac Catheterization ,medicine.medical_specialty ,medicine.drug_class ,Hypertension, Pulmonary ,medicine.medical_treatment ,Critical Care and Intensive Care Medicine ,Severity of Illness Index ,Pulmonary Disease, Chronic Obstructive ,Internal medicine ,medicine.artery ,Natriuretic Peptide, Brain ,medicine ,Natriuretic peptide ,Humans ,Prospective Studies ,Pulmonary Wedge Pressure ,Cardiac Output ,Cardiac catheterization ,Lung ,medicine.diagnostic_test ,business.industry ,Respiratory disease ,Middle Aged ,Prognosis ,medicine.disease ,Brain natriuretic peptide ,Pulmonary hypertension ,Plethysmography ,Survival Rate ,Endocrinology ,medicine.anatomical_structure ,Pulmonary artery ,Disease Progression ,Exercise Test ,Cardiology ,Female ,business ,Biomarkers ,Follow-Up Studies - Abstract
The detection of pulmonary hypertension in patients with chronic lung disease has prognostic implications. The brain natriuretic peptide (BNP) has been suggested as a noninvasive marker for the presence and severity of pulmonary hypertension.We evaluated circulating BNP levels as a parameter for the presence and severity of pulmonary hypertension in patients with chronic lung disease.BNP levels were measured in 176 consecutive patients with various pulmonary diseases. Right heart catheterization, lung functional testing, and a 6-min walk test were performed. The mean follow-up time was nearly 1 yr.Significant pulmonary hypertension (mean pulmonary artery pressure35 mm Hg) was diagnosed in more than one-fourth of patients and led to decreased exercise tolerance and life expectancy. Elevated BNP concentrations identified significant pulmonary hypertension with a sensitivity of 0.85 and specificity of 0.88 and predicted mortality. Moreover, BNP served as a risk factor of death independent of lung functional impairment or hypoxemia in uni- and multivariate analysis.We suggest BNP as a prognostic marker and as screening parameter for significant pulmonary hypertension in chronic lung disease.
- Published
- 2006
38. Human Herpesvirus 6 in Bronchalveolar Lavage Fluid after Lung Transplantation: A Risk Factor for Bronchiolitis Obliterans Syndrome?
- Author
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Gundula Jaeger, Martin Schwaiblmair, Claus Neurohr, P Huppmann, Lorenz Frey, Peter Überfuhr, Hanno Leuchte, Jürgen Behr, Iris Bittmann, Rudolf Hatz, and Bruno Reichart
- Subjects
Adult ,Male ,Epstein-Barr Virus Infections ,Adenoviridae Infections ,Herpesvirus 2, Human ,Herpesvirus 6, Human ,viruses ,medicine.medical_treatment ,Roseolovirus Infections ,Bronchiolitis obliterans ,Herpesvirus 1, Human ,Polymerase Chain Reaction ,Virus ,Cohort Studies ,Postoperative Complications ,Risk Factors ,Humans ,Immunology and Allergy ,Medicine ,Lung transplantation ,Pharmacology (medical) ,Risk factor ,Bronchiolitis Obliterans ,Transplantation ,medicine.diagnostic_test ,biology ,business.industry ,Incidence ,Respiratory disease ,Herpes Simplex ,Middle Aged ,medicine.disease ,biology.organism_classification ,humanities ,Bronchoalveolar lavage ,Cytomegalovirus Infections ,DNA, Viral ,Immunology ,Female ,Human herpesvirus 6 ,business ,Bronchoalveolar Lavage Fluid ,Lung Transplantation - Abstract
Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS.
- Published
- 2005
39. Pulmonary Arterial Hypertension: Diagnosis with Fast Perfusion MR Imaging and High-Spatial-Resolution MR Angiography—Preliminary Experience
- Author
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Maximilian F. Reiser, Bernd Kuehn, Juergen Behr, Stefan O. Schoenberg, Hanno Leuchte, Armin Huber, Konstantin Nikolaou, Frank Rosa, Juergen Scheidler, Ulrike I. Attenberger, Olaf Dietrich, and R. Baumgartner
- Subjects
Male ,medicine.medical_specialty ,Hypertension, Pulmonary ,Perfusion scanning ,Scintigraphy ,Diagnosis, Differential ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,medicine.anatomical_structure ,Embolism ,Angiography ,Female ,Radiology ,business ,Perfusion ,Magnetic Resonance Angiography ,Artery - Abstract
To determine prospectively the accuracy of a magnetic resonance (MR) perfusion imaging and MR angiography protocol for differentiation of chronic thromboembolic pulmonary arterial hypertension (CTEPH) and primary pulmonary hypertension (PPH) by using parallel acquisition techniques.The study was approved by the institution's internal review board, and all patients gave written consent prior to participation. A total of 29 patients (16 women; mean age, 54 years +/- 17 [+/- standard deviation]; 13 men; mean age, 57 years +/- 15) with known pulmonary hypertension were examined with a 1.5-T MR imager. MR perfusion imaging (temporal resolution, 1.1 seconds per phase) and MR angiography (matrix, 512; voxel size, 1.0 x 0.7 x 1.6 mm) were performed with parallel acquisition techniques. Dynamic perfusion images and reformatted three-dimensional MR angiograms were analyzed for occlusive and nonocclusive changes of the pulmonary arteries, including perfusion defects, caliber irregularities, and intravascular thrombi. MR perfusion imaging results were compared with those of radionuclide perfusion scintigraphy, and MR angiography results were compared with those of digital subtraction angiography (DSA) and/or contrast material-enhanced multi-detector row computed tomography (CT). Sensitivity, specificity, and diagnostic accuracy of MR perfusion imaging and MR angiography were calculated. Receiver operator characteristic analyses were performed to compare the diagnostic value of MR angiography, MR perfusion imaging, and both modalities combined. For MR angiography and MR perfusion imaging, kappa values were used to assess interobserver agreement.A correct diagnosis was made in 26 (90%) of 29 patients by using this comprehensive MR imaging protocol. Results of MR perfusion imaging demonstrated 79% agreement (ie, identical diagnosis on a per-patient basis) with those of perfusion scintigraphy, and results of MR angiography demonstrated 86% agreement with those of DSA and/or CT angiography. Interobserver agreement was good for both MR perfusion imaging and MR angiography (kappa = 0.63 and 0.70, respectively).The combination of fast MR perfusion imaging and high-spatial-resolution MR angiography with parallel acquisition techniques enables the differentiation of PPH from CTEPH with high accuracy.
- Published
- 2005
40. Iloprost for idiopathic pulmonary arterial hypertension
- Author
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Jürgen Behr and Hanno Leuchte
- Subjects
medicine.medical_specialty ,Sildenafil ,Hypertension, Pulmonary ,Vasodilator Agents ,Prostacyclin ,Disease ,chemistry.chemical_compound ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Iloprost ,Clinical Trials as Topic ,business.industry ,Endothelin receptor antagonist ,Idiopathic Pulmonary Arterial Hypertension ,General Medicine ,medicine.disease ,Pulmonary hypertension ,Bosentan ,chemistry ,cardiovascular system ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Idiopathic pulmonary arterial hypertension is a rare but serious and life-threatening disease that leads to right heart failure and death within 2.8 years without specific treatment. This review focuses on the stable prostacyclin analog iloprost, its biologic action and pharmacology and, finally, on its clinical development, efficacy and safety in patients with idiopathic pulmonary arterial hypertension, which led to its approval for this indication. Furthermore, this review assesses the role of iloprost compared with other newly developed drugs, such as the endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil, as well as other modes of application of prostacyclin and its analogs for the treatment of idiopathic pulmonary arterial hypertension. Based on the different modes of action of these substances, a combination of these treatments could be most promising for the future.
- Published
- 2005
41. Clinical significance of brain natriuretic peptide in primary pulmonary hypertension
- Author
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Tilman Kolbe, Claus Neurohr, R. Baumgartner, Martin Schwaiblmair, Michael Holzapfel, Isabelle Béatrice Ding, Hanno Leuchte, Jürgen Behr, and Michael Vogeser
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Hypertension, Pulmonary ,Cardiac index ,Severity of Illness Index ,Internal medicine ,medicine.artery ,Natriuretic Peptide, Brain ,medicine ,Natriuretic peptide ,Humans ,business.industry ,Central venous pressure ,Middle Aged ,medicine.disease ,Brain natriuretic peptide ,Pulmonary hypertension ,medicine.anatomical_structure ,Circulatory system ,Pulmonary artery ,Exercise Test ,Cardiology ,Vascular resistance ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
ObjectivesThe aim of this study was to investigate the potential role of brain natriuretic peptide (BNP) levels in the assessment of functional status and right heart performance in primary pulmonary hypertension (PPH).BackgroundPrimary pulmonary hypertension is a progressive disease leading to right heart failure and death. Right heart catheterization and maximal or submaximal exercise tests are employed to assess the course of the disease and the effect of therapeutic interventions. Additional noninvasive and reproducible parameters would be helpful to assess the status of patients with PPH. The natriuretic peptide system is up-regulated in PPH patients. Brain natriuretic peptide (BNP) is produced from the cardiac ventricles and elevated in PPH. The aim of our study was to evaluate the clinical significance of BNP in PPH patients.MethodsCorrelation analysis was performed for plasma BNP levels of 28 PPH patients and World Health Organization (WHO) functional class (WHO-class), distance walked in 6 min, peak oxygen uptake (peak Vo2), and oxygen pulse during spiroergometry and various hemodynamic parameters, including pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), right atrial pressure (RAP), and cardiac index.ResultsThe BNP levels were inversely correlated with the 6-min walk (r = −0.70; p < 0.001) and peak Vo2(r = −0.61; p < 0.01), and positive correlation was observed with WHO-class (r = 0.79; p < 0.001). Moreover, BNP levels were also correlated to PVR (r = 0.61; p < 0.01), PAP (r = 0.48; p < 0.05), and RAP (r = 0.78; p < 0.01), and were inversely related to cardiac index (r = −0.48; p < 0.05).ConclusionsOur data suggest that plasma BNP levels are closely related to the functional impairment of PPH patients and parallel the extent of pulmonary hemodynamic changes and right heart failure. Serial measurements of plasma BNP concentrations may help improve the management of PPH patients.
- Published
- 2004
42. Hemodynamic Response to Sildenafil, Nitric Oxide, and Iloprost in Primary Pulmonary Hypertension
- Author
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Tilman Kolbe, Claus Neurohr, Jürgen Behr, Martin Schwaiblmair, Hanno Leuchte, and R. Baumgartner
- Subjects
Male ,Cardiac Catheterization ,Vasodilator Agents ,Administration, Oral ,Hemodynamics ,Vasodilation ,Critical Care and Intensive Care Medicine ,Severity of Illness Index ,Piperazines ,chemistry.chemical_compound ,Medicine ,Prospective Studies ,Sulfones ,Middle Aged ,respiratory system ,Treatment Outcome ,medicine.anatomical_structure ,Anesthesia ,cardiovascular system ,Female ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Adult ,Pulmonary and Respiratory Medicine ,Sildenafil ,Hypertension, Pulmonary ,Nitric Oxide ,Risk Assessment ,Drug Administration Schedule ,Sampling Studies ,Sildenafil Citrate ,Nitric oxide ,medicine.artery ,Administration, Inhalation ,Humans ,Iloprost ,Dose-Response Relationship, Drug ,business.industry ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,chemistry ,Purines ,Pulmonary artery ,Vascular resistance ,Vascular Resistance ,business ,Follow-Up Studies - Abstract
Different vasodilators and different routes of application are used for the treatment of primary pulmonary hypertension (PPH). Recently, sildenafil, a phosphodiesterase-V inhibitor, has been shown to have beneficial hemodynamic effects in PPH. However, the hemodynamic effects of sildenafil have not been characterized and compared to other vasodilators such as inhaled nitric oxide (iNO) or iloprost in PPH in the same group of patients.We investigated prospectively 10 consecutive patients with PPH using iNO, iloprost aerosol, and oral sildenafil to test acute hemodynamic response during right-heart catheterization.iNO, iloprost aerosol, and sildenafil caused a significant fall of mean pulmonary artery pressure and pulmonary vascular resistance (PVR) [p0.05]. Correspondingly, cardiac output and mixed venous saturation increased slightly in all groups. Systemic arterial pressure and vascular resistance were mainly unaltered. Using a PVR reduction ofor =20% to define a significant response, 7 of 10 patients were responders to iloprost aerosol, whereas 4 of 10 patients responded to iNO and oral sildenafil. Improvement of oxygenation as indicated by an increase of arterial oxygen tension was observed with iloprost aerosol (p0.01).All of the three substances, iNO, iloprost aerosol, and oral sildenafil, significantly improved pulmonary hemodynamics in patients with PPH. The most prominent hemodynamic effects and improvement of oxygenation were observed with iloprost aerosol.
- Published
- 2004
43. Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics
- Author
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F. Grimminger, Hanno Leuchte, C. Knothe, A. Benzing, Andreas Günther, Dieter Walmrath, Werner Seeger, D. Pappert, Udo Obertacke, and T. Schmehl
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Pulmonary and Respiratory Medicine ,ARDS ,APACHE II ,Respiratory distress ,Septic shock ,business.industry ,Lung injury ,medicine.disease ,Oxygen tension ,Shock (circulatory) ,Anesthesia ,medicine ,medicine.symptom ,business ,Tidal volume - Abstract
Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics. D. Walmrath, F. Grimminger, D. Pappert, C. Knothe, U. Obertacke, A. Benzing, A. Gunther, T. Schmehl, H. Leuchte, W. Seeger. #ERS Journals Ltd 2002. ABSTRACT: The aim of the present study was to investigate the feasibility and efficacy of bronchoscopic surfactant administration in a noncontrolled multicentre study in five university centres. A total number of 27 patients, suffering from severe acute respiratory distress syndrome (meaniSEM lung injury score: 3.15i0.06) and septic shock (Acute Physiology and Chronic Health Evaluation (APACHE) II score at study entry 33.2i1.3, lactate 4.3i0.6 mmol?L -1 ) were studied. The patients were ventilated with a mean tidal volume of 11.0i0.5 mL?kg -1 body weight (bw), either volume or pressure controlled, with 16.3i2.8 cmH2O positive end-expiratory pressure, for an average of 3.5i0.3 days at study entry. A natural bovine surfactant extract (300 mg?kg -1 bw Alveofact1; mean total volume 378 mL) was delivered in divided doses to each segment of the lungs via flexible bronchoscope withiny45 min. No untoward effects on gas exchange, lung mechanics and haemodynamics were noted during the procedure of surfactant administration. Within 12 h the oxygen tension in arterial blood/inspiratory oxygen fraction increased from a mean of 109i8 mmHg to 210i20 mmHg (pv0.001). In seven patients, in whom gas exchange again deteriorated with further progression of the disease, a second surfactant dose of 200 mg?kg -1 was administered 18-24 h after the first application, again improving arterial oxygenation. A total of 15 patients survived the 28-day study period (mortality rate 44.4%, compared to a calculated risk of death for the given APACHE II scores of 74.0i3.5%), with all causes of death being nonrespiratory. The bronchoscopic application of a high dose of natural surfactant in patients with severe acute respiratory distress syndrome and septic shock is both feasible and safe, resulting in a pronounced improvement in gas exchange. Eur Respir J 2002; 19: 805-810.
- Published
- 2002
44. Combination of nonspecific PDE inhibitors with inhaled prostacyclin in experimental pulmonary hypertension
- Author
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Dieter Walmrath, Norbert Weissmann, Axel Roehl, Friedrich Grimminger, Hanno Leuchte, Ralph T. Schermuly, Werner Seeger, and Hossein Ardeschir Ghofrani
- Subjects
Pulmonary and Respiratory Medicine ,Phosphodiesterase Inhibitors ,Physiology ,Hypertension, Pulmonary ,Vasodilation ,Prostacyclin ,Pharmacology ,Theophylline ,Physiology (medical) ,medicine.artery ,Administration, Inhalation ,Cyclic AMP ,Pressure ,Ventilation-Perfusion Ratio ,medicine ,Animals ,Vasoconstrictor Agents ,Pentoxifylline ,Antihypertensive Agents ,Dose-Response Relationship, Drug ,Inhalation ,Pulmonary Gas Exchange ,business.industry ,Nebulizers and Vaporizers ,Dipyridamole ,Cell Biology ,medicine.disease ,Epoprostenol ,Pulmonary hypertension ,medicine.anatomical_structure ,15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ,Anesthesia ,Circulatory system ,Pulmonary artery ,Drug Therapy, Combination ,lipids (amino acids, peptides, and proteins) ,Rabbits ,business ,medicine.drug ,Blood vessel - Abstract
Inhalation of aerosolized prostacyclin (PGI2) exerts selective pulmonary vasodilation, but its effect is rapidly lost after termination of nebulization. Amplification of the vasodilatory response to inhaled PGI2 might be achieved by phosphodiesterase (PDE) inhibitors to stabilize its second messenger, cAMP. We established stable pulmonary hypertension in perfused rabbit lungs by continuous infusion of U-46619. Short-term (10-min) aerosolization maneuvers of PGI2 effected a rapid, moderate decrease in pulmonary arterial pressure, with post-PGI2 vasorelaxation being lost within 10–15 min, accompanied by a marginal reduction in shunt flow. Preceding administration of subthreshold doses of the PDE inhibitors theophylline, dipyridamole, and pentoxifylline via the intravascular or inhalational route, which per se did not influence pulmonary hemodynamics, caused more than doubling of the immediate pulmonary arterial pressure drop in response to PGI2 and marked prolongation of the post-PGI2 vasorelaxation to >60 min (all PDE inhibitors via both routes of application). This was accompanied by a reduction in shunt flow in the case of aerosolized theophylline (27.5%), pentoxifylline (30.5%), and dipyridamole (33.4%). Coaerosolization of PGI2 and PDE inhibitors may be considered as a therapeutic strategy in pulmonary hypertension.
- Published
- 2001
45. Treatment goals of pulmonary hypertension
- Author
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Luke Howard, Michael A. Mathier, Sean Gaine, Olivier Sitbon, Hanno Leuchte, Victor F. Tapson, Vallerie V. McLaughlin, Massimillano Palazzini, Myung H. Park, Sanjay Mehta, McLaughlin VV, Gaine SP, Howard LS, Leuchte HH, Mathier MA, Mehta S, Palazzini M, Park MH, Tapson VF, and Sitbon O
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Hypertension, Pulmonary ,Cardiac index ,Hemodynamics ,Treatment goals ,hemodynamics ,Text mining ,Cardiac magnetic resonance imaging ,pulmonary arterial hypertension ,Internal medicine ,medicine ,Natriuretic peptide ,Animals ,Humans ,6-min walk distance ,medicine.diagnostic_test ,business.industry ,Central venous pressure ,medicine.disease ,Pulmonary hypertension ,PULMONARY HYPERTENSION ,right ventricular function ,Treatment Outcome ,Physical therapy ,Cardiology ,Exercise Test ,Cardiology and Cardiovascular Medicine ,business ,Goals ,Biomarkers - Abstract
Özet– Pulmoner hipertansiyon alanındaki önemli gelişmelerden sonra, en önemli görevlerden biri uzun dönem sonuçlarla ilişkili kinik tedavi hedeflerini belirleme gereksinimidir. Modifiye New York Kalp Cemiyeti fonksiyonel sınıf I veya II, 380 metreden fazla 6 dakika yürüme mesafesine ulaşma, ekokardiyografide sağ ventrikül boyutunun ve fonksiyonunun normalleşmesi, B-tip natriüretik peptit düzeyinin azalması ya da normalleşmesi ve sağ atriyal basıncının 8 mmHg’den düşük ve kardiyak indeksin 2,5 L/dk/m2 ’den büyük olması güncel hedeflerdir. Bununla birlikte, egzersiz kapasitesi ve sağ kalp fonksiyonu gibi uzun dönem sonuçlarla daha fazla ilişkili olan parametreleri hedefleyen daha güçlü ve net sınırlarla çizen “eşiğin” daha yüksek tutulması gerektiği açık hale gelmektedir; Özellikle, manyetik rezonans görüntüleme ve BNP/N-terminal pro B tip natriüretik peptit gibi doğru ve noninvaziv olarak sağ ventrikül fonksiyonunu belirleyen testler, temel belirleyiciler ve tedavi hedefleri olarak hizmet etmek için umut verici göstergeler olarak ortaya çıkmaktadır. Ayrıca, sonuçlar üzerine odaklı çalışmalar tek başına hiçbir testin güvenilir bir şekilde uzun vadeli prognostik belirteç olarak kullanılamayacağını ve birleşik tedavi hedeflerinin uzun dönem sonuçlarının daha iyi öngördüreceğini gösterdi. Yeniden düzenlenen tedavi hedeflerinin şunlar olduğu ileri sürülmüştür: Modifiye New York Kalp Cemiyeti fonksiyonel sınıf I veya II, ≥380 ve 440 m arasındaki 6 dakika yürüme mesafesi, kardiyopulmoner egzersiz testi-15 ml/d/kg’dan fazla tepe oksijen tüketim ölçümü ve 45 l/dak’dan az karbondioksit için solunum eşdeğeri, normale yakın BNP değeri, ile normal/normale yakın sağ ventrikül boyut ve fonksiyonlarını gösteren ekokardiyografi ve/veya kardiyak manyetik rezonans görüntüleme ve 8 mmHg’den az sağ atriyal basınçla ve 2,5-3 l/dak/m²’den fazla kardiyak indeksle birlikte sağ ventrikül fonksiyonunun normalleştiğini gösteren hemodinamik parametreler. (J Am Coll Cardiol 2013;62:D73–81) With significant therapeutic advances in the field of pulmonary arterial hypertension, the need to identify clinically relevant treatment goals that correlate with long-term outcome has emerged as 1 of the most critical tasks. Current goals include achieving modified New York Heart Association functional class I or II, 6-min walk distance >380 m, normalization of right ventricular size and function on echocardiograph, a decreasing or normalization of B-type natriuretic peptide (BNP), and hemodynamics with right atrial pressure 2.5 L/dk/m2. However, to more effectively prognosticate in the current era of complex treatments, it is becoming clear that the "bar" needs to be set higher, with more robust and clearer delineations aimed at parameters that correlate with long-term outcome; namely, exercise capacity and right heart function. Specifically, tests that accurately and noninvasively determine right ventricular function, such as cardiac magnetic resonance imaging and BNP/N-terminal pro-B-type natriuretic peptide, are emerging as promising indicators to serve as baseline predictors and treatment targets. Furthermore, studies focusing on outcomes have shown that no single test can reliably serve as a long-term prognostic marker and that composite treatment goals are more predictive of long-term outcome. It has been proposed that treatment goals be revised to include the following: modified New York Heart Association functional class I or II, 6-min walk distance 380 to 440 m, cardiopulmonary exercise test-measured peak oxygen consumption >15 ml/min/kg and ventilatory equivalent for carbon dioxide 2.5 to 3.0 l/min/m2. (J Am Coll Cardiol 2013;62:D73-81) ©2013 by the American College of Cardiology Foundation.
- Published
- 2013
46. Kongenitale ösophagotracheale Fistel im Erwachsenenalter
- Author
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Hanno Leuchte, J Callegari, T Wiesböck, and R Baumgartner
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2013
47. The Munich-LTX-Score: predictor for survival after lung transplantation
- Author
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Patrick, Huppmann, Claus, Neurohr, Stefan, Leuschner, Hanno, Leuchte, Rainer, Baumgartner, Gregor, Zimmermann, Tobias, Meis, Werner, von Wulffen, Peter, Überfuhr, Rudolf, Hatz, Lorenz, Frey, and Jürgen, Behr
- Subjects
Adult ,Graft Rejection ,Male ,Adolescent ,Middle Aged ,Prognosis ,Survival Rate ,Young Adult ,Risk Factors ,Multivariate Analysis ,Humans ,Female ,Child ,Bronchiolitis Obliterans ,Follow-Up Studies ,Lung Transplantation - Abstract
The purpose of this study was to create a prognostic score calculated one yr after LTX based on post-transplant factors inclusive of donor and recipient characteristics that could be used to predict long-term survival in patients after lung transplantation (LTX).Uni- and multivariate analysis in 206 consecutive LTX patients identified independent risk factors for post-transplant mortality and onset of bronchiolitis obliterans syndrome. Munich-LTX-Score is devised by summing up each identified risk factor.Multivariate analyses revealed acute rejection, lymphocytic bronchiolitis, donor age ≥ 55 yr, and HLA-A ≥ 2-/DR ≥ 2 mismatch and single LTX to be independent negative predictors for long-term survival (p0.05). Munich-LTX-Score identified three discrete groups: low-, moderate-, and high risk. The actuarial five-yr survival after score calculation one yr after LTX of the entire cohort was 58%, compared with 91% in low-, 54% in moderate-, and 0% in the high-risk group (p0.001).Within our cohort of patients calculation of the Munich-LTX-Score, consisting of donor-, recipient-, and post-transplant characteristics, one yr after LTX allowed to predict long-term survival of lung transplant recipients. After prospective validation, this score could identify patients who may benefit from intensified surveillance after LTX.
- Published
- 2011
48. Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?
- Author
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Claus, Neurohr, Anna L, Hoffmann, Patrick, Huppmann, Vivian A, Herrera, Franziska, Ihle, Stefan, Leuschner, Werner, von Wulffen, Tobias, Meis, Carlos, Baezner, Hanno, Leuchte, Rainer, Baumgartner, Gregor, Zimmermann, and Juergen, Behr
- Subjects
Adult ,Pulmonary and Respiratory Medicine ,Lung Neoplasms ,Time Factors ,Vital Capacity ,Respiratory System Agents ,Forced Expiratory Volume ,Germany ,Humans ,Lymphangioleiomyomatosis ,Lung ,Respiratory Tract Infections ,Sirolimus ,lcsh:RC705-779 ,Research ,Pneumonia ,Recovery of Function ,lcsh:Diseases of the respiratory system ,Middle Aged ,Respiratory Function Tests ,respiratory tract diseases ,tuberous sclerosis complex ,lung transplantation ,guidelines ,management ,efficacy ,registry ,Treatment Outcome ,Disease Progression ,Exercise Test ,Female - Abstract
Background Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM. Methods Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed. Results The mean loss of FEV1 was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV1 of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV1 and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months ΔFEV1: 220 ± 82 ml, p = 0.024; 6 months ΔFEV1: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy. Conclusions Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.
- Published
- 2011
49. Rechtsherzkatheter-Untersuchung bei pulmonaler Hypertonie
- Author
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Ekkehard Grünig, Juergen Behr, Marius M. Hoeper, Hossein Ardeschir Ghofrani, R Ewert, M Halank, Alexander Schmeisser, Horst Olschewski, Rudolf Speich, Hanno Leuchte, Stephan Rosenkranz, Christian Opitz, H Wilkens, University of Zurich, and Rosenkranz, S
- Subjects
Right heart catheterization ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Hemodynamics ,610 Medicine & health ,General Medicine ,2700 General Medicine ,medicine.disease ,Pulmonary hypertension ,medicine.anatomical_structure ,Internal medicine ,Predictive value of tests ,Anesthesia ,medicine ,Cardiology ,Vascular resistance ,Differential diagnosis ,10029 Clinic and Policlinic for Internal Medicine ,Pulmonary wedge pressure ,business ,Cardiac catheterization - Published
- 2011
50. Effect of inpatient rehabilitation on quality of life and exercise capacity in long-term lung transplant survivors: a prospective, randomized study
- Author
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G. Zimmermann, Stephan Czerner, Rudolf Hatz, Claus Neurohr, P Huppmann, Lorenz Frey, Peter Ueberfuhr, Jürgen Behr, Hanno Leuchte, F. Ihle, Rainier Baumgartner, Bernd Sczepanski, Iris Bittmann, and Klaus Kenn
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Randomization ,medicine.medical_treatment ,Physical exercise ,Walking ,law.invention ,Randomized controlled trial ,Quality of life ,law ,Statistical significance ,Internal medicine ,Surveys and Questionnaires ,Outpatients ,medicine ,Lung transplantation ,Humans ,Prospective Studies ,Prospective cohort study ,Physical Therapy Modalities ,Transplantation ,Inpatients ,Exercise Tolerance ,business.industry ,Middle Aged ,Respiratory Function Tests ,Treatment Outcome ,Physical therapy ,Quality of Life ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,business ,Lung Transplantation - Abstract
Background The purpose of this study was to examine the effect of an inpatient rehabilitation program on health-related quality of life (HRQOL) and exercise capacity (EC) in long-term (>1 year after lung transplantation) survivors (LTSs) in comparison to a control group (CG). Methods Sixty LTSs, 4.5 ± 3.2 years after lung transplantation (LTx), were randomly assigned to two equally sized groups that were stratified for gender and underlying disease. Thirty LTSs (age 49 ± 13 years, 13 male and 17 females, 19 double LTxs, 7 BOS Stage ≥1) attended an inpatient rehabilitation program (intervention group, IG) for 23 ± 5 days. The CG (age 50 ± 12 years, 13 males and 17 females, 20 double LTxs, 2 BOS Stage ≥1) received medical standard therapy (physiotherapy). Patients were evaluated by cardiopulmonary exercise testing, 6-minute walk test (6MWT), SF-36, SGRQ and the Quality of Life Profile for Chronic Diseases questionnaire before and after (18 ± 3 days) the program. Results The groups were statistically indistinguishable in terms of clinical data. Each treatment group significantly improved their sub-maximal EC (6MWT: IG, 493 ± 90 m vs 538 ± 90 m, p < 0.001; CG, 490 ± 88 m vs 514 ± 89 m, p < 0.001) and maximal EC (VO2peak: IG, 17.0 vs 18.5 ml/min/kg, p = 0.039; CG, 18.0 vs 19.5 ml/min/kg, p = 0.005), without reaching statistical significance between the groups. In both study groups, patients HRQOL tended to improve. Significant correlations were found between EC parameters and HRQOL scales. Conclusions Our data suggest that structured physical training may improve exercise tolerance in LTS. Our study results did not demonstrate a significant benefit of an inpatient over an outpatient exercise program.
- Published
- 2010
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