Further, levels of Sirt1, a type III histone deacetylase which negatively regulates MMP9 transcription [7], were reported to be downregulated in patients with severe COPD but not in healthy smokers, suggesting a role for endogenous oxidative stress from activated neutrophils and macrophages in the reduction of Sirt1 [7]. Here, SIRT1 is linked to chronic obstructive pulmonary disease.