RESEARCH ARTICLE
Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias Marius M. Hoeper1*, Juergen Behr2, Matthias Held3, Ekkehard Grunig4, C. Dario Vizza5, Anton Vonk-Noordegraaf6, Tobias J. Lange7, Martin Claussen8, Christian Grohé9, Hans Klose10, Karen M. Olsson1, Thomas Zelniker11, Claus Neurohr2, Oliver Distler12, Hubert Wirtz13, Christian Opitz14, Doerte Huscher15, David Pittrow16, J. Simon R. Gibbs17
OPEN ACCESS Citation: Hoeper MM, Behr J, Held M, Grunig E, Vizza CD, Vonk-Noordegraaf A, et al. (2015) Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias. PLoS ONE 10(12): e0141911. doi:10.1371/journal. pone.0141911 Editor: Masataka Kuwana, Nippon Medical School Graduate School of Medicine, JAPAN Received: August 17, 2015 Accepted: October 14, 2015
1 Department of Respiratory Medicine and German Center of Lung Research (DZL), Hannover Medical School, Hannover, Germany, 2 Department of Internal Medicine V, University of Munich, Munich, Germany, 3 Department of Internal Medicine, Respiratory Medicine and Cardiology, Mission Medical Hospital, Würzburg, Germany, 4 University Hospital Heidelberg, Heidelberg, Germany, 5 Department of Cardiovascular and Respiratory Diseases, Sapienza, University of Rome, Rome, Italy, 6 Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands, 7 Department of Internal Medicine II, Division of Pneumology, University Medical Center Regensburg, Regensburg, Germany, 8 LungenClinic, Grosshansdorf, Germany, 9 Department of Respiratory Medicine, ELK Thorax Centre, Berlin, Germany, 10 University Medical Center Hamburg-Eppendorf, Center of Oncology, Department of Respiratory Medicine, Hamburg, Germany, 11 Department of Cardiology, Angiology and Pneumology, University of Heidelberg, Heidelberg, Germany, 12 Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland, 13 Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany, 14 Department of Cardiology, DRK Kliniken Berlin Köpenick, Berlin, Germany, 15 Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Epidemiology unit, German Rheumatism Research Centre, Berlin, Germany, 16 Institute for Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany, 17 Department of Cardiology, National Heart & Lung Institute; Imperial College London, London, United Kingdom *
[email protected]
Abstract
Published: December 2, 2015 Copyright: © 2015 Hoeper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Due to ethical restrictions, data are available upon request. Although our data are anonymized (Center ID and patient-ID) we are dealing with rare diseases, which is why we are concerned with placing the data into an online repository. These concerns are shared by the lead IRB of this project (Ethics committee, Technical University Dresden, Germany), in particular as the informed consent form that all patients have signed does not include the possibility of an online repository of individual patient data. Interested researchers may submit requests for minimized anonymous dataset by
Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies.
Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP).
Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with
PLOS ONE | DOI:10.1371/journal.pone.0141911 December 2, 2015
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PH in Chronic Fibrosing Idiopathic Interstitial Pneumonias
contacting Professor Marius Hoeper (hoeper.
[email protected]). Funding: The registry is investigator-initiated and currently supported by unrestricted grants from Actelion, Bayer, GSK, and Pfizer. The funders were not involved at all in this analysis or in preparing the manuscript. The authors without the help of medical writers wrote the paper. Competing Interests: MM Hoeper has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, and Pfizer. J Behr has received honoraria for lectures and/or consultancy from Actelion, Bayer, Boehringer, Gilead, GSK, InterMune, Lilly, MSD, Novartis, and Pfizer. M Held has received speaker fees and honoraria for consultations from Actelion, Bayer, Boehringer Ingelheim Pharma, Glaxo Smith Kline, Lilly, Janssen, Novartis, Pfizer, Nycomed, Roche and Servier. E Grunig has received honorariums for consultations and/or speaking at conferences from Actelion, Bayer, Gilead, GSK, Lilly, Milteney, Novartis, Pfizer and Rotex Medica and funding for clinical trials by Actelion, Bayer, GSK, Encysive, Lilly and Pfizer. Carmine Dario Vizza has received fees for serving as a speaker, consultant and an advisory board member, from the following companies: Actelion, Dompè, GSK, Italfarmaco, Lilly, Pfizer, United Therapeutics. A Vonk-Noordegraaf reports receiving lecture fees from Actelion, Bayer, GlaxoSmithKline, Lilly and Pfizer, industry advisory board from Actelion and Bayer and serving on steering committees for Actelion, Bayer, GlaxoSmithKline and Pfizer. TJ Lange has received speaker fees, honoraria for consultations and/or research, and educational grants from Actelion, AOP Orphan Pharmaceuticals, Bayer, GSK, Pfizer, and United Therapeutics. M Claussen has received speaker fees and/or honoraria for consultations from Actelion, Bayer and Pfizer. C Grohé has received speaker fees and honoraria for consultations from Actelion, Bayer, Gilead, GSK, Lilly and Pfizer. H Klose has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis, Pfizer, United Therapeutics and research grants from Actelion. KM Olsson has received speaker fees from Actelion, Bayer and Lilly. T Zelniker has no conflict of interest. C Neurohr has no conflict of interest. O Distler has received speaker fees, honoraria for consultations and/or grant support from 4D Science, Actelion, Active Biotec, BayerSchering, Biogen, Biovitrium, BMS, Boehringer, EpiPharm, Ergonex, GSK, Inventiva, Medac, Novartis, Pfizer, Pharmacyclics, Roche/Genentech, Sanofi/Genzyme, Serodapharm, Sinoxa and United BioSource Corporation. H Wirtz has received speaker fees and honoraria for consultations from Bayer, Novartis, GSK, Boehringer Ingelheim Pharma. CF
phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p
