Matched-Comparative Modeling of Normal and Diseased Human Airway Responses Using a Microengineered Breathing Lung Chip

Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smokeinduced injury responses under physiological breathing conditions in humans due to patienttopatient variability. Here, we show that a small airwayonachip device lined by living human bronchiolar epithelium from normal or COPD patients can be connected to an instrument that `` breathes'' whole cigarette smoke in and out of the chips to study smokeinduced pathophysiology in vitro. This technology enables true matched comparisons of biological responses by culturing cells from the same individual with or without smoke exposure. These studies led to identification of ciliary micropathologies, COPDspecific molecular signatures, and epithelial responses to smoke generated by electronic cigarettes. The smoking airwayonachip represents a tool to study normal and diseasespecific responses of the human lung to inhaled smoke across molecular, cellular and tissuelevel responses in an organrelevant context.