Dysfunctional autophagy has also been associated with defects in specific cell types of the airway. The secretory cells of the airway, such as the club and goblet cells, play an important role in host defense during infection. Autophagy has been recently shown to be required to maintain the function of club cells, independent of CS exposure [146]. Mice deficient in autophagy protein Atg5, demonstrate a diminished expression of the host defense protein secretoglobulin family 1A member 1 (SCGB1A1) and surfactant proteins A1 and D (Sftpa1 and Sftpd), as well as abnormal club cell morphology [146]. Moreover, a diminished SCGB1A1 expression in club cells correlates with evidence of reduced autophagy in lung tissue from COPD former smokers [146]. CS exposure has also been demonstrated to cause the accumulation of damaged mitochondrial via impaired mitophagy, which has been demonstrated to play a role in COPD pathogenesis disease progression [147,148]. Thus, it can be postulated that CS-induced autophagy dysfunction would further deteriorate the structure and function of club cells, resulting in altered or diminished host defense mechanisms in COPD subjects.