The lung is a unique organ, as it is constantly exposed to air and airborne pollutants including oxidant gases such as highly reactive nitrogen dioxide and ozone, particulates, viruses, other microbes, immune activators and irritants. Defense from these pollutants is provided by a number of cell types that include epithelial cells and macrophages. Differentiated ciliated airway epithelial cells contain cilia, specialized organelles that beat in waves to propel pathogens and inhaled particles trapped in the mucous layer out of the airways [1]. Secretory epithelial cells produce mucins, and an array of anti-microbial products [2]. Airway epithelial cells also express hydrogen peroxide (H 2 O 2)-producing dual oxidases (DUOX) providing defense from microbes and other irritants [3]. Located in the distal alveolar lung regions, type II epithelial cells produce surfactant proteins with anti-microbial or surfactant lowering activities [4]. Type II epithelial cells have been estimated to constitute 60% of alveolar epithelial cells and 10–15% of all lung cells. These cells are highly bioenergetically active due to their role in surfactant production, barrier protection, metabolism of xenobiotics, and as progenitor cells to replace damaged alveolar epithelial cells. The functions of distal epithelial cells and other cell types allow the lung to function to exchange oxygen and carbon dioxide to allow for normal aerobic function [5].

The high metabolic demand on airway and alveolar type II epithelial cells which secrete mucins, surfactant proteins, cytokines, etc., can create stress in the endoplasmic reticulum (ER). A tightly regulated, evolutionary conserved stress response termed the unfolded protein response (UPR), is triggered to rectify the stress, thereby allowing adaptation. However, when the stress is excessive, apoptosis occurs [6]. ER stress has become a well-recognized feature of chronic lung diseases. Less well recognized is the fact that protein folding within the ER creates oxidants, and that the ER environment is oxidizing to allow disulfide bond formation in proteins to occur. Therefore, altered redox-based processes that accompany ER stress have the potential to contribute to chronic lung diseases.