Qualified biomarkers of potential harm (BoPH) are useful in evaluating the beneficial effects of abstinence from cigarette smoking or switching to potentially reduced risk tobacco products. We benchmarked BoPH changes in a 14-day smoking abstinence study in two age groups and used those BoPH to assess the effects of Vuse ENDS products. This smoking abstinence study was conducted under confinement conditions, and enrolled 70 subjects into younger (24-34 years, n=33) and older (35-60 years, n=37) groups. Several biomarkers of exposure and BoPH were evaluated.

Significant declines in Leukotriene E4 (LTE4), 2,3-dinor-thromboxane B2 (2,3-d-TXB2), neutrophils, white blood cells (WBC) and select arterial blood cell parameters were observed in both age groups at Day 7 and 14 compared to baseline, while other BoPH, (e.g. arterial blood gases, fractional exhaled nitric oxide) showed age-related effects. In a separate confinement study where smokers abstained from smoking or switched to three Vuse ENDS products for seven days, complete blood counts were analyzed. The results showed that WBC, neutrophil and red blood cell (RBC) counts, along with hematocrit and hemoglobin levels, decreased in smokers who were switched to Vuse ENDS to the same extent observed in seven days of smoking abstinence. The BoPH assessed in these studies are indicators of platelet activation (2,3-d-TXB2) and inflammation (LTE4, WBC and neutrophils), and provide useful clinical risk markers for assessing candidate modified risk tobacco products in short-term studies. In each study, rapid and reproducible reductions in LTE4, 2,3-d-TXB2, WBC and neutrophil counts were consistently detected following smoking abstinence or switching to Vuse ENDS, indicating the value of these markers as BoPH.