Smoking-Related Disease Risk Reduction Potential of ENDPs

Abstract Smoking is a major cause of noncommunicable diseases, including lung cancer, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases (CVDs). While the risk of smoking-related disease increases with the number of cigarettes smoked and the duration of smoking, it also decreases upon smoking cessation. The development of electronic nicotine delivery products (ENDPs) is aimed at providing smokers who will not quit with alternatives to cigarettes that present less risk of harm and smoking-related disease than cigarettes. It is necessary to rigorously assess the risk reduction potential of ENDPs through various types of studies to ensure ENDPs meet this objective. Premarket assessment of the disease risk reduction potential of ENDPs is hampered by (i) the dearth of biomarkers of potential harm that are predictive of future disease development, (ii) the latency of disease manifestation, and (iii) the slow reduction in excess risk upon cessation and, a fortiori, upon switching from cigarette smoking to the use of ENDPs. Long-term epidemiological data will allow to definitively verify that an ENDP reduces the risk of smoking-related disease compared with cigarettes and, if it does, to quantify the reduction in excess disease risk associated with an ENDP. For this to be possible, the ENDP would need to be available in the market and used exclusively by a large proportion of current smokers. Here, we propose that a mechanism-based approach represents a solid alternative to demonstrate in a premarket setting that switching to an ENDP is likely to significantly reduce the risk of smoking-related disease. This approach is based on the causal chain of events that leads from smoking to disease and leverages both nonclinical and clinical studies as well as the principles of systems toxicology. In this chapter, we review the available scientific evidence in the context of lung cancer, COPD, and CVD for both heated tobacco products and e-vapor products.