Update on therapeutic management of idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive diffuse parenchymal lung disease of unknown origin, with a mortality rate exceeding that of many cancers. The diagnostic process is complex and relies on the clinician integrating clinical, laboratory, radiological, and histological data. In the last decade, major advances in our understanding of the pathogenesis of IPF have shifted the paradigm from a primarily inflammatory process evolving to fibrosis to a condition driven by aberrant wound healing following alveolar epithelial cell injury that results in scarring of the lung, architectural distortion, and irreversible loss of function. Improved understanding of disease pathogenesis has led to the identification of several therapeutic targets and the design of high-quality clinical trials evaluating novel compounds. However, the results of these studies have been mostly disappointing, probably due to the plethora of mediators, growth factors, and signaling pathways involved in the fibrotic process. Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. This is a major breakthrough. Nevertheless, we still have a long way to go. In fact, neither pirfenidone nor nintedanib is a cure for IPF, and most patients continue to progress despite treatment. As such, comprehensive care of patients with IPF, including management of concomitant conditions and physical debility, as well as timely referral for lung transplantation, remains essential. Several agents with a high potential are currently being tested, and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.

Keywords: nintedanib; pirfenidone; pulmonary fibrosis; therapy; treatment.

Figure 1

High-resolution computed tomography image demonstrating usual interstitial pneumonia pattern, with bilateral, basal, and subpleural predominant reticular abnormality and honeycombing (arrows).

Figure 2

Surgical lung biopsy specimen demonstrating usual interstitial pneumonia pattern, characterized by the abrupt transition from fibrotic tissue with honeycombing and few pale fibroblastic foci (bottom) to nearly normal lung (top). Note: Hematoxylin and eosin, 20×. Courtesy of Giulio Rossi, Modena, Italy.