Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, debilitating disease of unknown etiology with a median survival from diagnosis of 3-5 years. The IPF lung is characterized by extensive histological changes that include formation of fibroblasts/myofibroblasts foci, accumulation of extracellular matrix and areas of aberrant remodeling interspersed with normal lung parenchyma. Current disease pathogenesis assumes an aberrant wound healing process in response to multiple cycles of epithelial injury in genetically predisposed individuals. A plethora of pathways including persistent TGFB1 and extracellular matrix activation, aberrant recapitulation of developmental programs, endoplasmic reticulum stress, immune deregulation and cellular senescence including telomere attrition, impaired cellular bioenergetics and defective mitochondrial homeostasis, has been implicated in IPF pathogenesis. The implementation of advanced methodological “omics” tools led to key pathogenic discoveries, identification of novel therapeutic targets and improved phenotyping of disease progression patterns. Disease definition and diagnostic criteria have significantly improved over last few years, allowing clinicians to conduct large multicenter clinical trials investigating efficacy of several therapeutic compounds in highly characterized patients with IPF. Despite these revelations, IPF still presents a major bottleneck for chest physicians and researchers due to its appreciable heterogeneity in disease course and treatment response. Currently, there are only two available drugs, pirfenidone and nintedanib that showed promising results in slowing down disease progression of patients with IPF. However, both of these drugs do not improve lung function, thus at best case leaving patients with significant pulmonary disability while at the same time have been associated with considerable side-effects that deteriorate patients’ quality of life. As a result, IPF currently represents the non-cancer disease with the gravest prognosis, responsible for 40.000 deaths each year, same as breast cancer. In addition, current physiologic and molecular biomarkers present with major limitations in accurately predicting disease behavior, thus allowing clinicians to modify disease management accordingly. This Research Topic aims to summarize important aspects of IPF pathogenesis and treatment, highlight knowledge gaps and provide recommendations for strategic approaches to better define disease pathogenesis and develop more effective therapies. In the dawn of the “fibromics” era, the need for disease stratification based on molecular phenotypes and implementation of personalized therapeutic approaches is still unmet and sorely needed.