It is critical to note that the epithelial dysfunction observed in these animals, as well as part of the association of COPD risk with specific CHRNA loci, emerges independently of cigarette smoke (Parker et al., 2019; Routhier et al., 2021; Siedlinski et al., 2013), indicating that nAchR signaling is critical to maintain homeostasis not only in the context of oxidative stress, but under homeostatic conditions. Here, CHRNA4 is linked to chronic obstructive pulmonary disease.