Cigarette smoking is well established as the cause of the majority of cases
of emphysema. However, the mechanisms by which exposure of the lung to smo
ke causes the destruction of the lung parenchyma are not known. Oxidation p
robably contributes to the progression of this disease in several different
ways. Oxidants present in the smoke itself or those generated by inflammat
ory cells in response to the particulate phase of the smoke inactivate prot
einase inhibitors, and the increased inflammatory cells produce and release
additional proteinases. The expression and activity of metalloproteinases,
which have recently been implicated in the pathogenesis of emphysema, are
regulated by redox status. Finally, oxidative damage to structural proteins
may potentiate their degradation by the increased proteolytic burden.