Consequently, in the present study, the 90 DMGs, regarding RAGE-mediated airway inflammation induced by CS exposure, were initially selected using a novel intersection model, and the functional DNA methylated modification in 14 targeted genes were subsequently identified, especially hypomethylation in CXCL1, TLR6 and OSM promoters, which might significantly contribute to RAGE-mediated airway inflammation in COPD via a network of signaling pathways, such as MAPK, TNF, TLRs, ILs, etc. Here, TLR6 is linked to inflammatory response.