In particular, COPD-EVs compared to HS-EVs significantly increased the subset of CD133+ CICs and specifically the subset of metastatic CD133+CXCR4+ cells only in HBEC-6 cells, harboring p53 and KRASV12 mutation, and in HBEC-KRASV12high cells, whereas modest effect on CICs was observed in HBEC 1 immortalized cells and in transformed HBEC lines harboring sh-p53 or KRASV12 oncogenic mutation only (HBEC 3 and 5) (Fig. 2C). This evidence concerns the gene TP53 and chronic obstructive pulmonary disease.