In this study, we aimed (I) to investigate the prevalence of CHIP in COPD patients, (II) to investigate CHIP-mediated molecular consequences by DNA methylation, metabolomics, and cytokine analyses, (III) to correlate these with lung function parameters, and (IV) to evaluate the causality in macrophages derived from human peripheral blood mononuclear cells (PBMCs) and human precision cut lung slides (PCLS). This evidence concerns the gene STUB1 and chronic obstructive pulmonary disease.