RESUMO
Cigarette smoking (CS) remains a cause of considerable morbidity and mortality, despite recent progress in smoking cessation in the United States. Epidemiologic studies in humans have reported associations between CS and development of acute respiratory distress syndrome (ARDS) after a number of inciting risk factors. We have assessed the effects of CS exposure on lung vascular permeability and inflammation in mice and found that both acute and sustained CS exposure increased the severity of acute lung injury caused by subsequent intrapulmonary instillation of lipopolysaccharide. In addition to enhanced inflammation, CS exposure directly impaired lung endothelial cell barrier function. Our results indicate that mouse strains differ in susceptibility to CS exacerbation of acute lung injury and that there are differences in transcriptomic effects of CS. These results demonstrate the biologic basis for the association of CS with development of ARDS. We propose that CS be considered a cause of heterogeneity of ARDS phenotypes and that this be recorded as a risk factor in the design of clinical trials.
