Table 9.

Summary of studies on mechanisms.

Ref. No.	Study Country Year	Experimental type	Main Findings
[116]	2019 Hayata et al.	In vivo and In vitro	Among several periodontal pathogens, exposure to elevated levels of Fn was the most potent in inducing the production of pro-inflammatory cytokines by human bronchial and pharyngeal epithelial cells, which may lead to exacerbation of COPD.
[117]	2022 Suzuki et al.	In vivo and In vitro	Fn may contribute to the onset of pulmonary diseases via MMP-9 expression through extracellular-regulated kinase 1/2 and NF-ĸB activation.
[118]	2022 Suzuki et al.	In vivo	The administration of Fn to elastase-treated mice enhanced inflammatory responses, production of alveolar wall destruction factors, progression of emphysema, and recruitment of mucin.
[119]	2020 Li et al.	In vitro	Fn frequently coexisted with Pa in the respiratory tract of AECOPD patients, and co-culturing the two bacteria promoted bacterial proliferation and induced antibiotic tolerance by forming a dense biofilm surrounded by excessive Pel and Psl polysaccharides, which might be induced by FadA.
[120]	2021 Li et al.	In vitro	Fn could co-aggregate with Pa to synergistically invade into pulmonary epithelial cells and transiently resist P. aeruginosa-induced cytotoxic damage to amplify IL-6 and TNF-α associated inflammation in pulmonary epithelial cells simultaneously infected with P. aeruginosa and F. nucleatum.
[121]	2021 Takahashi et al.	In vitro	The culture supernatant of the Fn upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells, and induced IL-6 and IL-8 production by A549 alveolar epithelial cells, BEAS-2B bronchial epithelial cells, Detroit 562 pharyngeal epithelial cells, and primary alveolar epithelial cells.
[122]	2020 Rosa et al.	In vivo	The association COPD and periodontitis decreased macrophages, TNF-α and INF-γ in BAL, when compared to the COPD group maintaining emphysema levels by alveolar enlargement reorganization of collagen fibers and also mean linear intercept and mucus.
[124]	2019 Han et al.	In vivo	Although COPD had no effect on periodontitis, 25-OHD3 treatment significantly reduced inflammation by decreasing serum levels of RANKL, TNF-α and IL-1 and increasing that of IL-10, while reducing alveolar bone loss and slightly improving lung function in the periodontitis group or COPD+periodontitis group.
[125]	2018 Miller et al.	In vitro	The presence of Ab increased the abundance of Pg in model dual-species communities,suggesting that both Pg and Ab adapt to each other and have synergistic potential for increased pathogenicity.