Abstract
The pathogenesis of chronic obstructive pulmonary disease remains elusive; investigators in the field have struggled to decipher the cellular and molecular processes underlying chronic bronchitis and emphysema. Studies in the past 20 years have underscored that the tissue destruction, notably in emphysema, involves a multitude of injurious stresses, with progressive engagement of endogenous destructive processes triggered by decades of exposure to cigarette smoke and/or pollutants. These lead to an aged lung, with evidence of macromolecular damage that is unlikely to repair. Here we discuss these key pathogenetic elements in the context of organismal evolution as this concept may best capture the challenges facing chronic obstructive pulmonary disease.