Swarnakar Rajesh, Garje Yogesh, Markandeywar Neeraj, Mehta Suyog
Department of Respiratory, Critical Care, Sleep Medicine and Interventional Pulmonology, Getwell Hospital and Research Institute, Dhantoli, Maharashtra, India.
Medical Affairs, Sun Pharma Industries Ltd, India.
Lung India. 2022 May-Jun;39(3):279-285. doi: 10.4103/lungindia.lungindia_89_22.
In coronavirus disease 2019 (COVID-19) patients, dysregulated release of matrix metalloproteinases occurs during the inflammatory phase of acute respiratory distress syndrome (ARDS), resulting in epithelial and endothelial injury with excessive fibroproliferation. COVID-19 resembles idiopathic pulmonary fibrosis (IPF) in several aspects. The fibrotic response in IPF is driven primarily by an abnormally activated alveolar epithelial cells (AECs) which release cytokines to activate fibroblasts. Endoplasmic reticulum (ER) stress is postulated to be one of the early triggers in both diseases. Systemic sclerosis (SSc) is a heterogeneous autoimmune rare connective tissue characterised by fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a common complication and the leading cause of SSc-related death. Several corollaries have been discussed in this paper for new drug development based on the pathogenic events in these three disorders associated with pulmonary fibrosis. A careful consideration of the similarities and differences in the pathogenic events associated with the development of lung fibrosis in post-COVID patients, IPF patients and patients with SSc-ILD may pave the way for precision medicine. Several questions need to be answered through research, which include the potential role of antifibrotics in managing IPF, SSc-ILD and post-COVID fibrosis. Many trials that are underway will ultimately shed light on their potency and place in therapy.
在2019冠状病毒病（COVID-19）患者中，基质金属蛋白酶的释放失调发生在急性呼吸窘迫综合征（ARDS）的炎症期，导致上皮和内皮损伤以及过度的纤维增生。COVID-19在几个方面类似于特发性肺纤维化（IPF）。IPF中的纤维化反应主要由异常激活的肺泡上皮细胞（AECs）驱动，这些细胞释放细胞因子以激活成纤维细胞。内质网（ER）应激被认为是这两种疾病的早期触发因素之一。系统性硬化症（SSc）是一种异质性自身免疫性罕见结缔组织病，其特征是皮肤和内脏器官纤维化。间质性肺疾病（ILD）是常见并发症，也是SSc相关死亡的主要原因。本文基于这三种与肺纤维化相关疾病的致病事件，讨论了新药研发的几个推论。仔细考虑COVID后患者、IPF患者和SSc-ILD患者肺纤维化发展相关致病事件的异同，可能为精准医学铺平道路。需要通过研究回答几个问题，其中包括抗纤维化药物在治疗IPF、SSc-ILD和COVID后纤维化中的潜在作用。许多正在进行的试验最终将阐明它们的效力和在治疗中的地位。
