Indeed, we recently found that cigarette smoke induced shedding of the ADAM17 substrate amphiregulin (AREG), and IL-6R was enhanced in differentiated bronchial cells in culture obtained from COPD patients compared to non-COPD, suggesting that epigenetic factors controlling the activity of the ADAM17/EGFR axis are affected in COPD [87]. This evidence concerns the gene AREG and chronic obstructive pulmonary disease.