Abstract::Background: Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease characterized
by the depletion of alveolar epithelial cells (AECs) and the pathological accumulation of extracellular
matrix (ECM). Despite its high mortality rate, the molecular drivers of PF progression remain partially understood.
Recent evidence suggests that pyroptosis, a pro-inflammatory programmed cell death, plays a pivotal
role in orchestrating the inflammatory cascade and fibrotic remodeling in the lung. Methods: This study
employed bibliometric and visual analysis via CiteSpace 6.2.4 to systematically map the research landscape of
pyroptosis in PF using the Web of Science Core Collection (2010-2025). Based on the identified hotspots, a
comprehensive review of the molecular activation pathways and cell-specific mechanisms was conducted.
Results: Bibliometric analysis (Modularity Q=0.5381, Silhouette S=0.8236) revealed a significant shift in
research focus from basic pathological descriptions (2010-2015) to detailed pyroptotic mechanisms (2015-
2020), with immune checkpoint inhibitors emerging as the latest frontier since 2020. Mechanistically, we propose
an "Initiation-Amplification-Persistence" model: AEC pyroptosis initiates epithelial barrier disruption;
macrophage pyroptosis amplifies the inflammatory storm and polarizes the immune microenvironment; and
fibroblast activation sustains ECM deposition. Furthermore, we summarized potential therapeutic interventions,
including small molecule synthetic compounds (Nintedanib, Pirfenidone, MCC950, VX-765, etc.), natural
products (Lycorine, Tanshinone IIA, etc.) and biologically active substances (Canakinumab, Anakinra)
that exhibit multi-pathway synergistic effects. Conclusion: Targeting the pyroptosis signaling axis offers a
promising strategy for reversing PF progression. Future research should prioritize the identification of pyroptosis-
related biomarkers and the development of lung-targeted delivery systems to facilitate clinical translation
and precision intervention.