The aims of this study were: (1) to characterize the exosomal miRNA profile of foamy macrophages compared to normal macrophages using miRNA sequencing; (2) to evaluate the functional impact of let-7—selected as a representative miRNA identified in aim 1—on lipid accumulation, RNF8/RXR expression, and inflammatory cytokine production (IL-6, TNF-α) in foamy macrophages through transfection experiments; and (3) to investigate the PPAR/RXR pathway as a key mediator of let-7’s effects in the pathogenesis of COPD. Here, TNF is linked to chronic obstructive pulmonary disease.