Bringing Light to Chronic Obstructive Pulmonary Disease Pathogenesis and Resilience

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.

Keywords: aging; cigarette smoke; oxidative stress; senescence; stress.

Figure 1.

The proposed three stages of the evolution of chronic obstructive pulmonary disease (COPD), which include lung responses driven by environmental stresses (stage 1), progressive amplification of injury allowing for the progression of the disease (stage 2), and a later stage of consolidation (stage 3). The multiple areas of investigation in COPD are outlined in the lower half of the figure. Dashed lines are meant to represent that each stage may prolong over time with the potential for intersections among all stages.