Innovative in vitro method to study ventilator induced lung injury

Abstract

Mechanical ventilation is a life-saving therapy for critically ill patients, alleviating the work of breathing and sup­porting adequate gas exchange. However, mechanical ventilation can cause ventilator induced lung injury (VILI) by baro/volu- and atelectrauma, lead to acute respiratory distress syndrome (ARDS), and substantially increase mortality. There is a need for specific biomarkers and novel research platforms for VILI/ARDS research to study these detrimental disorders and seek ways to avoid or prevent them. Previous in vitro studies on bronchial epithelium, cultured in air-liquid interface (ALI) conditions, have generally utilized static or constant pressure. We have developed a Cyclical Pressure ALI Device (CPAD) that enables cyclical stress on ALI cultured human bronchial cells with the aim of mimicking the effects of mechanical ventilation. Using CPAD we were able to analyze differentially expressed VILI/ARDS and innate immunity associated genes along with increased expression of associated proteins. CPAD provides an easy and accessible way to analyze functional and phenotypic changes that occur during VILI and may provide a platform for future drug testing.