Transcriptome analysis to investigate COPD exacerbations to influenza infection

Lung infection by influenza A viruses is a common cause of disease exacerbations in patients with chronic obstructive pulmonary disease (COPD), however, this process is difficult to study in human patients. Here we used a microfluidic human lung airway-on-a-chip (Airway Chip) lined by primary human bronchial epithelium interfaced with primary human pulmonary microvascular endothelium to model this process in vitro. Airway Chips containing bronchial epithelial cells from COPD patients successfully replicated the increased sensitivity to the lung airway to infection by both influenza H1N1 and H3N2 viruses compared to chips lined by epithelium from healthy donors, including enhanced viral loads and increased production of inflammatory cytokines. Transcriptomics analysis of the healthy and COPD epithelium following infection with influenza H1N1 virus on-chip resulted in identification of several novel markers of COPD Primary human lung bronchial-airway epithelial basal cells and primary diseased human lung bronchial-airway epithelial basal cells were used to generate human airway air-liquid (ALI) culture. Then these cells were infected wth influenza A virus, with MOCK infection and PolyIC as controls. Samples were harvested 4 h and 18 post infection for RNA-seq analysis.