Clinically, disease states and environmental factors, such as smoking, all play a major role in the increase of dead space. Increases in dead space can be seen in lung disease states including emphysema, pneumonia, and acute respiratory distress syndrome (ARDS). Emphysema results in the enlargement of air spaces and decreases in the diffusing capacity of the alveolar membrane due to the destruction of alveolar walls. In ARDS there is endothelial damage leading to an increase in the alveolar-capillary permeability, thereby leading to leakage of protein-rich fluid into the alveolar. This results in the formation of intra-alveolar hyaline membranes, which decrease the exchange of CO2 and O2 in the lung contributing to a larger dead space. Studies looking at the causes of death in this disease have shown an increase in dead space in the non-survivors versus survivors. The strongest association of an increased volume of dead space with mortality risk is seen in patients with ARDS.[9]