Figure 4.

Pathogenic triad of COPD: oxidative stress, protease–antiprotease imbalance, and inflammation. Oxidative stress, protease–antiprotease imbalance and inflammation each are important in the pathogenesis of COPD; however, they constantly interact and may at times overlap with each other in the overall pathogenesis of COPD. As a consequence of oxidative stress, in particular cigarette smoking-induced oxidative stress, apoptosis, autophagy, and senescence are each potential lung cell fates. Senescent cells express a pro-inflammatory phenotype. Proteases, such as neutrophil elastase, have been shown in vitro to induce airway epithelial apoptosis,⁸³ but this relationship has not yet been specifically demonstrated in human subjects. Listed in italics are the genetic polymorphisms that have been reported and discussed in this review, to be associated with COPD or emphysema in that area of the pathogenic triad.