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Translating Basic Research Into Clinical Practice |

Molecular Endotyping of Pulmonary Fibrosis

Amanda T. Goodwin, MBChB; Gisli Jenkins, PhD
Author and Funding Information

CORRESPONDENCE TO: Gisli Jenkins, PhD, Centre for Respiratory Research, University of Nottingham, Clinical Sciences Building, City Hospital Campus, Hucknall Road, Nottingham, NG5 1PB, England


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(1):228-237. doi:10.1378/chest.15-1511
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Idiopathic pulmonary fibrosis (IPF) is a devastating and incurable progressive fibrotic lung condition associated with a significant disease burden. In recent years there has been an exponential increase in the number of preclinical and clinical studies performed in IPF. IPF is defined according to rigid diagnostic criteria; hence, a significant subset of patients with unclassifiable disease has been excluded from these studies. The traditional diagnostic classification of all progressive fibrotic lung diseases uses specific clinical, radiological, and histopathological features to define each condition. However, the considerable heterogeneity within each form of pulmonary fibrosis has raised the possibility of distinct pathophysiological mechanisms culminating in a common phenotype. Thus, the classification of fibrotic lung diseases according to the driving molecular mechanisms rather than specific user-defined histopathological and radiological features could improve several aspects of clinical care. Discoveries from basic science research have defined multiple complex molecular pathways involved in the pathogenesis of pulmonary fibrosis that may provide markers for the molecular endotyping of this disease. In addition, these molecular pathways have revealed potential therapeutic targets. Reclassifying progressive fibrotic lung diseases according to molecular endotypes may allow for more accurate assessment of prognosis and individualized treatment. Furthermore, recent developments that have been applied to a narrow group of patients with IPF may be applicable to those with other progressive fibrotic lung diseases. This review presents the latest developments from translational research in this area and explains how molecular endotyping could revolutionize the diagnosis, stratification, and treatment of pulmonary fibrosis.

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