# Current advancements in the mechanisms and animal models of acute exacerbation of pulmonary fibrosis: a systematic review

## TL;DR

This paper reviews recent research on animal models and mechanisms of acute exacerbation in pulmonary fibrosis, highlighting key factors like inflammation and oxidative stress.

## Contribution

The study systematically reviews AE-PF models and mechanisms over 20 years, identifying bleomycin and lipopolysaccharide as a common experimental approach.

## Key findings

- Bleomycin combined with lipopolysaccharide is the most common model for AE-PF.
- Inflammation, immune imbalance, and oxidative stress are major mechanisms in AE-IPF.
- ER stress and alveolar epithelial cell apoptosis are also key factors in AE-IPF.

## Abstract

Characterized by sudden onset, accelerated disease progression, and high mortality rates, acute exacerbation (AE) represents the most critical clinical challenge faced by patients with idiopathic pulmonary fibrosis (IPF). The absence of standardized animal models that recapitulate human disease phenotypes remains a significant impediment to the study of AE-IPF. In this work, we conducted a systematic review of experimental protocols for acute exacerbation of pulmonary fibrosis (AE-PF) over the past 20 years relating to aspects such as animal species, drugs, drug doses, drug administration routes, and model characteristics, and summarized research progress on the mechanism underlying this condition. Statistical analysis revealed that bleomycin combined with lipopolysaccharide represents the predominant experimental paradigm for AE-PF, accounting for 26.3% (5/19) of all AE-PF models. Our analysis further showed that the major mechanisms involved in AE-IPF are inflammation, immune imbalance, oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis of alveolar epithelial cells.