NFE2L2 and pulmonary emphysema: Its importance was unmasked already in 2004 by Rangasamy et al. as the disruption of the Nrf2 gene in mice led to earlier-onset and more extensive emphysema in response to cigarette smoke compared to Nrf2 wild-type littermates, which signifies that mice lacking Nrf2 are more susceptible to CS-induced emphysema/oxidative stress (33).