On the contrary, in the more compromised peripheral airways, BMP4 levels are unchanged in smokers and COPD patients vs. control non-smokers and the reduced levels of chordin and CRIM1 may exert a less protective effect against fibrosis events and pro-proliferative actions, particularly in alveolar septa (endothelial and epithelial components) and lung macrophages [3,35,36,37]. This evidence concerns the gene CHRD and chronic obstructive pulmonary disease.