Cigarette smoke (CS) is a major driver of COPD development, and exposure to cigarette smoke can induce a chain of systemic responses that not only increase IL-33 production in epithelial and endothelial cells but also cause increased IL-33 expression in peripheral blood mononuclear cells (PBMC), which induces persistent activation of the immune system favoring COPD progression [56]. This evidence concerns the gene IL33 and chronic obstructive pulmonary disease.