Background: The chronic exposure to air pollution-derived fine particulate matter (PM2.5) is suspected of exacerbating and even causing chronic inflammatory lung diseases. However, the knowledge of the underlying mechanisms is still incomplete. Objectives: To assess transcriptomic alterations in human bronchial epithelial cells exposed to PM2.5 and better understand how this exposure may lead to a shift from healthy to COPD phenotype. Methods: Normal human bronchial epithelial (NHBE) or COPD cells were differentiated at the air-liquid interface and repeatedly exposed to PM2.5 for 72h. Their transcriptomes were analyzed using human pangenomic microarrays. Results: Basal transcriptomes of both control cell phenotypes were first compared and 1280 transcripts were significantly deregulated in COPD vs NHBE cells. The transcription of 1168 genes was significantly altered by PM2.5 exposure in NHBE cells. Interestingly, among these deregulated mRNA, a large number (679) were in common with those found in shift from NHBE to COPD phenotype. Indeed, within this set of genes, we observed increased expression of genes involved in inflammation (e.g. TGF-b, IL-17, IL-33, CXCL1, CXCL3, CXCL6, CXCL8, CXCL14, CCL20), as well as genes associated with extracellular matrix remodeling (e.g. EGF, FGF1, KRT4, MMP9, MMP 13, TIMP-1). By contrast, only 107 transcripts were modulated by PM2.5 in COPD cells, evidencing an exacerbation of COPD. These alterations were validated by RTqPCR and at functional protein level. Conclusions: Overall these results showed that the transcriptomic alterations induced by PM2.5 exposure deregulated key pathways involved in COPD pathogenesis.