Chronic obstructive and restrictive lung diseases are among the leading causes of mortality worldwide, where acute or recurrent episodes of respiratory exacerbations are not only responsible for significant health care costs and a poor quality of life, but also an increased risk of death [1,2,3,4]. The airway mucosa is a primary route of entry for pathogenic microorganisms (bacteria, virus and/or fungi) and represents an important barrier in preventing the entry of these infectious organisms. In the event that the pathogen evades this mucociliary defense mechanism, the airway epithelial cells utilize complex pathogen clearance mechanisms to restrict the life-threatening exacerbations, where these cells work in collaboration with our immune system, involving both innate and adaptive responses, to launch a robust immune response against the invading pathogens, which if successful, results in pathogen elimination or clearance. Thus, providing proof-of-concept evidence in support of autophagy augmentation strategies for alleviating respiratory exacerbations in chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and coronavirus disease-2019 (COVID-19).