Idiopathic pulmonary fibrosis: Disease mechanisms and drug development.
Idiopathic pulmonary fibrosis: Disease mechanisms and drug development.
复制标题
特发性肺纤维化：发病机制和药物开发。
DOI：
10.1016/j.pharmthera.2020.107798
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发表时间：
2021-06
影响因子：
13.5
通讯作者：
Ryerson CJ
中科院分区：
文献类型：
--
作者：
Spagnolo P;Kropski JA;Jones MG;Lee JS;Rossi G;Karampitsakos T;Maher TM;Tzouvelekis A;Ryerson CJ
特发性肺纤维化（IPF）是一种原因不明的慢性进行性疾病，其特征是肺实质持续瘢痕化，导致生活质量降低和早期死亡。IPF是一种年龄相关疾病，随着全球人口老龄化，预计IPF的经济负担在未来将稳步增加。IPF中纤维化的机制仍然难以确定，疾病发病机制的有利概念涉及遗传易感肺泡上皮的复发性微损伤，随后是以过度胶原沉积为特征的异常修复反应。吡非尼酮和尼达尼布因其能够减缓功能衰退和疾病进展而获批用于治疗IPF;然而，它们不能治愈IPF，并且与耐受性问题相关。本文就疾病发病机制的前沿研究如何转化为新的治疗靶点，从而促进药物的发现作一综述。IPF的治疗选择组合越来越多。然而，靶向参与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具有不同作用机制的治疗策略的组合。
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.
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影响因子：
30.8
作者：
Fingerlin, Tasha E.;Murphy, Elissa;Zhang, Weiming;Peljto, Anna L.;Brown, Kevin K.;Steele, Mark P.;Loyd, James E.;Cosgrove, Gregory P.;Lynch, David;Groshong, Steve;Collard, Harold R.;Wolters, Paul J.;Bradford, Williamson Z.;Kossen, Karl;Seiwert, Scott D.;du Bois, Roland M.;Garcia, Christine Kim;Devine, Megan S.;Gudmundsson, Gunnar;Isaksson, Helgi J.;Kaminski, Naftali;Zhang, Yingze;Gibson, Kevin F.;Lancaster, Lisa H.;Cogan, Joy D.;Mason, Wendi R.;Maher, Toby M.;Molyneaux, Philip L.;Wells, Athol U.;Moffatt, Miriam F.;Selman, Moises;Pardo, Annie;Kim, Dong Soon;Crapo, James D.;Make, Barry J.;Regan, Elizabeth A.;Walek, Dinesha S.;Daniel, Jerry J.;Kamatani, Yoichiro;Zelenika, Diana;Smith, Keith;McKean, David;Pedersen, Brent S.;Talbert, Janet;Kidd, Raven N.;Markin, Cheryl R.;Beckman, Kenneth B.;Lathrop, Mark;Schwarz, Marvin I.;Schwartz, David A.
通讯作者：
Schwartz, David A.
影响因子：
6.9
作者：
Galli, Jonathan A.;Pandya, Aloknath;Criner, Gerard J.
通讯作者：
Criner, Gerard J.
影响因子：
9.6
作者：
Canestaro, William J.;Forrester, Sara H.;Devine, Beth E.
通讯作者：
Devine, Beth E.
DOI：
10.1164/rccm.201810-1972oc
发表时间：
2019-07-15
影响因子：
24.7
作者：
Chen, Gang;Ribeiro, Carla M. P.;Boucher, Richard C.
通讯作者：
Boucher, Richard C.
DOI：
10.1164/rccm.200406-710st
发表时间：
2005-04-15
影响因子：
24.7
作者：
American Thoracic Society;European Respiratory Society
通讯作者：
European Respiratory Society