Chronic exposure to waterpipe smoke elicits immunomodulatory and carcinogenic effects in the lung

Previous reports showed that cigarette smoke exposed normal-appearing airways in phenotypically lung cancer-free smokers carry alterations that are characteristic of tumors – suggestive of an airway field of injury. Very little is known of the effects of the chronic consumption of other forms of tobacco, such as waterpipe smoke (WPS), on lung pathobiology. Here we studied normal-appearing airway brushings from waterpipe smokers and those who were not exposed to WPS. We find that WPS elicits a molecular field of injury with gene programs that are pertinent to lung carcinogenesis. Overall design: Bronchial epithelial brushings from normal-appearing airways were acquired from lung cancer-free and eligible patients during diagnostic bronchoscopy. We performed RNA-sequencing of bronchial airway epithelial brushings from five individuals who never smoked waterpipe and from four waterpipe smokers who smoked at least 100 waterpipes in their lifetime, including during the 12-month period prior to enrollment.