Post-ARDS Pulmonary Fibrosis: From Molecular Mechanisms to Clinical Management
Guiyang Jia, Zhikun Gan, Enhua Feng, Zhiyou Zheng, Erqin Song, Mingjiang Qian, Miao Chen, Guoyue LiuAbstract
Background
Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung injury caused by various factors, including infection, trauma and shock. The predominant pathological alteration in its late stages is pulmonary fibrosis (PF), characterised by progressive extracellular matrix deposition, architectural destruction and functional impairment. Particularly in COVID-19-induced ARDS, PF incidence has markedly increased, making it a major sequela impacting patients’ long-term quality of life.
Methods
This review systematically examines post-acute lung injury (ALI)/ARDS PF through three perspectives: pathogenesis, prediction and treatment.
Results
Mechanistically, the fibrotic process involves epithelial injury and mesenchymal transition, fibroblast activation with aberrant extracellular matrix remodelling, dysregulated inflammation with immune cell involvement and clinical management-related factors. For prediction, various biomarkers (including growth factors, matrix proteins and inflammatory markers) and imaging features (particularly high-resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) characteristics) demonstrate clinical value. Integrated multiparameter models incorporating artificial intelligence show promise for early identification and risk stratification of high-risk patients. Therapeutic strategies encompass anti-inflammatory approaches (e.g., corticosteroids and antioxidants), antifibrotic agents (pirfenidone and nintedanib), cell-based therapies (mesenchymal stem cells and exosomes) and emerging genetic/RNA interventions. However, specific preventive and therapeutic approaches tailored to the post-ALI/ARDS PF population remain inadequate in clinical practice.
Conclusions
Future research should focus on elucidating underlying mechanisms, refining early-warning systems, exploring personalised treatments and facilitating clinical translation. The ultimate goal is to transition from traditional supportive care to proactive prevention through enhanced clinical surveillance, early prediction and rational intervention, thereby preventing fibrosis progression and improving outcomes in ARDS survivors.