FIGURE 3.

Predisposition of the aged lung to chronic lung diseases such as COPD or idiopathic pulmonary fibrosis (IPF). The vulnerable aged lung is primed to oxidative stress, cell injury and disrepair, acting as the “first hit”. Environmental challenges such as cigarette smoking, air pollution or viral/bacterial infections may serve as “second hits” which worsen age-related events and contribute to persistently elevated oxidative stress levels, that overwhelms the (weakened) defence and repair pathways. Whereas increased demise of type-II alveolar epithelial cells (AECII) is a common feature in both diseases, in COPD, however, oxidative stress and its detrimental consequences also result in a loss of structural fibroblasts and septal endothelial cells, leading to an irreversible loss of lung tissue and progressive formation of emphysematous spaces. In IPF, death and loss of AECII triggers abnormal fibroblast proliferation, myofibroblast differentiation and irreversible scar tissue generation, with oxidative stress contributing to this process. The “origins” that predispose the ageing lung to develop either COPD or IPF after the decisive injury, remain elusive.