Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic lung disease with a median survival of 2.8 years. Although there have been many treatment trials of agents targeting profibrotic pathways, there remains no effective therapy for IPF outside of lung transplantation. Pulmonary hypertension (PH) occurs in patients with IPF (IPF-PH) and negatively affects clinical course and prognosis. Given the lack of reliably effective antifibrotic therapy, combined with a growing number of drugs effective for PH (occurring outside the context of IPF), many investigators have turned their focus to IPF-PH in the hopes of treating this potentially modifiable comorbid condition. In this manuscript, we review published data on IPF-PH including its epidemiology, pathogenesis, diagnosis, clinical markers of its presence, impact on prognosis, and potential treatments.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with a poor outcome. Recently, there has been a growing appreciation for the presence of secondary pulmonary hypertension in patients with IPF (IPF-PH), and research has begun in earnest to understand the effects of PH on the clinical course and outcome of patients with IPF. The pathogenesis of IPF-PH is unclear but may be related to intermittent hypoxia, loss of vascular density within the fibrotic parenchyma, vascular remodeling, or endothelial dysfunction. Elevated pulmonary pressures, confirmed by right heart catheterization (RHC), affects nearly one-half of IPF patients undergoing evaluation for lung transplantation candidacy. Doppler echocardiography (TTE) is a noninvasive and relatively inexpensive way to screen for IPF-PH, but it is notoriously inaccurate: nearly 50% of IPF patients have a greater than 10mmHg difference between TTE and RHC estimates. Other non-invasive markers of PH in IPF patients are imperfect as well, and there is little correlation between IPF severity and the presence of PH. The presence of PH significantly worsens prognosis in patients with IPF: nearly one-third of patients with IPF-PH die within one year of being diagnosed with PH. Although there are currently no proven effective therapies for IPF-PH, well-designed trials are underway. Additional research is needed to more clearly define the epidemiology and risk factors for IPF-PH and to identify effective treatments.

Keywords

pulmonary hypertension, idiopathic pulmonary fibrosis, echocardiography, right heart catheterization, sildenafil