In this study, we tested two environmental exposure stimuli, bacterial lipopolysaccharide (LPS) and house dust mite (HDM), in an in vitro model of primary human bronchial epithelial cells (HBECs) from 6 individuals, to identify differentially expressed genes using RNAseq analysis in response to these exposures both individually and in combination. Our findings illustrate that exposure mixtures increase the strength and complexity of transcriptomic responses in HBECs as compared to individual stimuli alone, and that asthmatic’s cells are more sensitive to these stimuli, eliciting a greater number of differentially expressed genes vs. controls. Our results provide a basis for future studies in this area, such as the expansion of this in vitro model to test multiple exposure combinations (i.e. the exposome) and their influence on molecular signaling in the bronchial epithelium.