Respiratory Disease Unit, Department of Cardiac Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Vanderbilt University Medical Center, Nashville, TN, United States.
Pharmacol Ther. 2021 Jun;222:107798. doi: 10.1016/j.pharmthera.2020.107798. Epub 2020 Dec 24.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown cause characterized by relentless scarring of the lung parenchyma leading to reduced quality of life and earlier mortality. IPF is an age-related disorder, and with the population aging worldwide, the economic burden of IPF is expected to steadily increase in the future. The mechanisms of fibrosis in IPF remain elusive, with favored concepts of disease pathogenesis involving recurrent microinjuries to a genetically predisposed alveolar epithelium, followed by an aberrant reparative response characterized by excessive collagen deposition. Pirfenidone and nintedanib are approved for treatment of IPF based on their ability to slow functional decline and disease progression; however, they do not offer a cure and are associated with tolerability issues. In this review, we critically discuss how cutting-edge research in disease pathogenesis may translate into identification of new therapeutic targets, thus facilitate drug discovery. There is a growing portfolio of treatment options for IPF. However, targeting the multitude of profibrotic cytokines and growth factors involved in disease pathogenesis may require a combination of therapeutic strategies with different mechanisms of action.
特发性肺纤维化（IPF）是一种病因不明的慢性进行性疾病，其特征为肺实质进行性瘢痕形成，导致生活质量下降和更早死亡。IPF 是一种与年龄相关的疾病，随着全球人口老龄化，IPF 的经济负担预计将在未来稳步增加。IPF 纤维化的机制仍不清楚，疾病发病机制的有利概念涉及反复对遗传易感性的肺泡上皮造成微损伤，随后是特征为胶原过度沉积的异常修复反应。吡非尼酮和尼达尼布基于其减缓功能下降和疾病进展的能力被批准用于治疗 IPF；然而，它们不能治愈疾病，并且与耐受性问题相关。在这篇综述中，我们批判性地讨论了疾病发病机制的前沿研究如何转化为新治疗靶点的鉴定，从而促进药物发现。目前有越来越多的 IPF 治疗选择。然而，针对涉及疾病发病机制的多种促纤维化细胞因子和生长因子可能需要多种作用机制的治疗策略组合。
