Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias

Abstract

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 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<0.001). Total lung capacity, NYHA class IV, and mixed-venous oxygen saturation were independent predictors of survival in patients with PH-IIP.

Conclusions: Patients with PH-IIP have a dismal prognosis. Our results suggest that pulmonary vasodilator therapy may be associated with short-term functional improvement in some of these patients but it is unclear whether this treatment affects survival.

Trial registration: clinicaltrials.gov NCT01347216.

Conflict of interest statement

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, Bayer-Schering, 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 Opitz has no personal conflicts of interest. His institution received speaker fees or honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis and Pfizer. D Huscher has received author honoraria from Actelion. D Pittrow has received speaker fees or honoraria for consultations from Actelion, AstraZeneca, Aspen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Genzyme, Novartis, and Pfizer. JSR Gibbs has received speaker fees and honoraria for consultations from Actelion, Bayer, Gilead, GSK, Lilly, Novartis and Pfizer. These commercial affiliations do not alter the authors adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Kaplan-Meier survival estimates in patients with pulmonary hypertension associated with chronic fibrosing idiopathic interstitial pneumonias (PH-IIP) and patients with idiopathic pulmonary arterial hypertension (IPAH).

Numbers at risk at baseline and after 1 year, 2 years, 3 years, 4 years and 5 years in the IPAH cohort were 786, 558, 382, 253, 154 and 43, respectively, and in the PH-IIP cohort 150, 84, 40, 21, 10 and 2, respectively.

Fig 2. Kaplan-Meier survival estimates in patients with pulmonary hypertension associated with chronic fibrosing idiopathic interstitial pneumonias (PH-IIP) stratified by clinical response at first follow-up defined as either improvement in 6 min walking distance by at least 20 m or improvement in NYHA functional class.

Numbers at risk at baseline and after 1 year, 2 years, 3 years, 4 years and 5 years in the “no response” cohort were 73, 50, 22, 11, 3 and 0, respectively, and in the “response” cohort were 48, 28, 15, 8, 5 and 2, respectively.