Current Understanding of Pulmonary Fibrosis: Pathogenesis, Diagnosis, and Therapeutic Approaches

Abstract

Pulmonary fibrosis (PF) is a terminal-stage lung change in interstitial lung disease. It is characterized by proliferation of fibroblasts and deposition of a large amount of extracellular matrix, accompanied by inflammatory damage and structural destruction, caused by various reasons. The prognosis of PF is poor, and the average survival time after diagnosis is 2.5-3.5 years. The pathogenesis of PF is not yet fully understood. Its main mechanisms are diverse and include damage to alveolar epithelial cells, aggregation and activation of inflammatory cells and chemokines, proliferation of fibroblasts, transformation of myofibroblasts, production and deposition of large amounts of collagen, autophagy, epithelial-mesenchymal transition (EMT), mitochondrial quality-control disorders, microRNA, and circular RNA. The diagnosis of PF is mainly based on the comprehensive evaluation of clinical manifestations, imaging characteristics, and histopathological examination. Medical and family history to determine all potential causes of PF. For PF of unknown etiology, one can refer to the Official Clinical Practice Guideline of idiopathic pulmonary fibrosis (IPF) for definitive diagnosis. In terms of treatment, modern medications such as pirfenidone and nintedanib can inhibit the progression of PF to some extent and improve lung function. However, there is no drug that can significantly improve PF, except for lung transplantation. In addition, many patients are forced to stop taking medication due to adverse reactions in clinical practice. Therefore, to better control the progression of disease, some new drugs have been developed based on the pathogenesis of PF. However, there is still controversy over their efficacy and widespread clinical application in PF, and the evidence is limited. The results of in vitro and in vivo experiments, as well as randomized clinical trials, indicate that traditional Chinese medicine (TCM) can improve PF by intervening in multiple pathways and targets. This study combines the pathogenesis and diagnosis of PF, focusing on the intervention mechanism and targets of TCM in the treatment of PF, so as to provide more options for clinical treatment and provide scientific basis for a new approach to better management of PF.

Keywords: TCM prescription; diagnosis; pathogenesis; pulmonary fibrosis; traditional Chinese medicine; treatment.

Figure 1

Main mechanisms of PF include damage to alveolar epithelial cells, aggregation and activation of inflammatory cells and chemokines, transformation of myofibroblasts, deposition of a large amount of ECM, autophagy, EMT, mitochondrial quality-control disorders, microRNA (miRNA), and circular RNA (cirRNA). PF: pulmonary fibrosis; EMT: epithelial–mesenchymal transition; ECM: extracellular matrix; TGF-β1: transforming growth factor-β1; CTGF: connective tissue growth factor; PDGF: platelet-derived growth factor; VEGF: vascular endothelial growth factor.