Two Decades of Experimental Insights Into Cigarette Smoke- and Extract-Induced Emphysema: A Bibliographic Review (2000–2025)

Background: Emphysema is a predominant pathological feature of COPD and is closely associated with cigarette smoke (CS) exposure. Cigarette smoke extract (CSE) provides a controlled in vitro platform for elucidating the molecular mechanisms underlying CS-induced pathology. In contrast, whole CS models more faithfully reproduce the chronic exposure dynamics and systemic effects characteristic of human smoking behaviour. Materials and Methods: A systematic search of PubMed and Scopus from 2000--2025 identified 6,192 records. After screening with the PECO framework and a PRISMA-based process, 66 studies that investigated CS- or CSE-induced emphysema met the inclusion criteria. Bibliometric analysis was performed via the Bibliometrix R package. Results: CS-induced emphysema research has been based mostly on North America and Asia, with a focus on the systemic or clinical features of the disease. In contrast, CSE-driven research has focused primarily on the same regions of Asia and has focused specifically on cellular and molecular processes, especially oxidative stress, apoptosis, and epigenetic regulation. The Shapiro–Wilk test confirmed that the bibliometric variables exhibited non normal distributions. Subsequent Spearman correlation analysis revealed significant associations among citation patterns, publication output, coauthorship networks, and keyword trends (p < 0.05). Conclusion: The CS and CSE models offer complementary insights into the processes of emphysema pathogenesis. CS models reflect chronic pathological changes, whereas CSE models define specific cellular and molecular mechanisms. Integration of these two approaches will hasten translational efforts in supporting targeted therapies for COPD .