A. Schematic depicting human cohort selection for RNA seq of bronchial brushings among those undergoing bronchoscopy. B. Heat map showing differentially expressed transcripts between human airways of waterpipe smokers compared to non-smokers. Columns indicate patient airways and rows indicate transcripts (red, relatively up-regulated; blue, down-regulated). C. Topological network analysis of genes associated with NRF2-mediated oxidative stress in human** airways of waterpipe smokers were derived using IPA. Predicated activation of NRF2-mediated oxidative stress based on the gene set is indicated by the orange color. D. Left: Kaplan–Meier of overall survival of patients from TCGA and PROSPECT cohorts stratified by median expression of the WPS-associated prognosis signature (red: relatively higher than the median; blue: lower than the median). Right: Lung adenocarcinoma prognosis signature was propagated and computed as described in Methods. The prognosis signature was then statistically compared between non-smokers (blue) and waterpipe smokers (red) using the Wilcoxon rank sum test. *, P < 0.05; **, P < 0.01; ***, P < 0.001.