Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

Abstract

The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI.

Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis

“…Idiopathic pulmonary fibrosis (IPF) is a common lethal disorder representing a form of interstitial lung disease (ILD) resulting from alveolar tissue remodeling and fibrosis leading to respiratory failure (1)(2)(3). While pulmonary inflammation and loss of lung architecture in IPF involve interactions among multiple cell types, recent studies provide increasing support for the concept that injury to the respiratory epithelium plays an important role in IPF pathogenesis (4,5).…”

Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis

“…In addition, chronic administration of several small-molecule inhibitors of TGF-β1 receptor (TβR) kinases has led to enhanced skin and colonic inflammation and abnormalities in cardiac valves (22,23). To minimize adverse consequences, an approach of blocking TGF-β1 activation in specific cell types using the unique pathway of α v β 6 -dependent latent TGF-β1 activation has developed and is currently in clinical trial (24). But this integrin is primarily expressed in epithelia of lung, kidney, and skin (25).…”

Altered Hypoxic–Adenosine Axis and Metabolism in Group III Pulmonary Hypertension

“…Patients with group III PH usually present with lower levels of mPAP compared with group I; however, the development of PH has devastating consequences to patients with CLD, and is thus considered the single most significant predictor of mortality in patients with CLD (4,6,7). Regardless of the strong association of PH and mortality, there are currently no effective treatments for IPF and its complications (3,8).…”