ABSTRACT: Background: Waterpipe (hookah, shisha, narghile), a worldwide, commonly used method to smoke tobacco, is considered “safe” by its users because the smoke is “filtered” by water before inhalation. Based on the knowledge that lung cells take the brunt of inhaled smoke, we hypothesized that even mild waterpipe smoking is associated with disordering of lung biology. Methods: Young (25±4 yr), mild (3.5±2.5 sessions/wk for 4.1±2.5 years) waterpipe smokers with no history of cigarette smoking (n=21) were assessed in comparison to nonsmokers (33±9 yr, n=19) for routine clinical paramters, lung epithelial lining fluid metabolome, small airway epithelial (SAE) cell differential and transcriptome, alveolar macrophage (AM) transcriptome, plasma endothelial cell microparticles (EMPs), cough and sputum scores, lung function, chest HRCT. Results: Compared to nonsmokers, waterpipe smokers had increased levels of blood carboxy-hemoglobin, an abnormal epithelial lining fluid metabolome profile, increased proportions of SAE secretory and intermediate cells, reduced proportions of ciliated and basal cells, markedly abnormal SAE and AM transcriptomes, elevated levels of EMPs derived from apoptotic pulmo-nary endothelium, more cough and sputum, and lower diffusion capacity (DLCO). Conclusions: Young, mild-use waterpipe-only smokers have a variety of abnormalities in multiple lung-related biologic and clinical parameters, suggesting that even limited waterpipe use may be linked to lung disease, i.e., waterpipe smoking may be associated with a significant public health risk.
