Biomarkers of Exposure and Potential Harm in Two Weeks of Smoking Abstinence: Changes in Biomarkers of Platelet Function, Oxidative Stress, and Inflammation

Abstract

: Chronic cigarette smoking is a major risk factor for many serious diseases. While complete cessation of smoking is the best option to reduce harm from smoking, adverse impacts of smoking on health could persist for several years after cessation. Therefore, Biomarkers of Potential Harm (BoPH) are useful in interim evaluations of the beneficial effects of smoking cessation or switching to potentially lower-risk tobacco products. A 14-day smoking abstinence study was conducted under clinical confinement conditions and enrolled 70 subjects into younger (24-34 years, n = 33) and older (35-60 years, n = 37) age cohorts. Biomarkers of Exposure (BoE), which indicate exposure to nicotine and other toxicants, were measured at baseline, 7 and 14 days. Several BoPH including previously identified eicosanoids (leukotriene 4 (LTE4) and 2,3-dinor thromboxane ₂ (2,3-d-TXB₂) and others were evaluated. Significant declines in BoE, LTE_4, 2,3-d-TXB₂, neutrophils, WBC and select RBC, and arterial blood gas parameters were observed in both age cohorts at Days 7 and 14 compared to baseline, while other BoPH (e.g., FeNO) showed age-related effects. Rapid and reproducible reductions in LTE₄, 2,3-d-TXB₂ WBC, and neutrophil counts were consistently detected following smoking abstinence, indicating the value of these markers as useful BoPH.

Keywords: 2,3-d-TXB2; LTE4; WBC; biomarkers of exposure; biomarkers of potential harm; neutrophils; smoking abstinence.

Figure 1

Study Design of Smoking Abstinence Study. The smoking abstinence study consisted of the 14-day clinical confinement of smokers to evaluate biomarker changes. Blood and urine samples were collected at baseline (Day -1) and Days 7 and 14 of smoking abstinence. Biomarker measurements were made at baseline after 7 days and/or 14 days of smoking abstinence, as indicated.

Figure 2

Change in leukotriene 4 (A) and 2,3-dinor-thromboxane B2 (B) levels following smoking abstinence. Leukotriene 4 (A) and 2,3-dinor-thromboxane B2 (B) levels rapidly decline following smoking abstinence. Urine samples from a 24 h period obtained at baseline Day 7 and Day 14 from smokers switched from usual brand (UB) cigarettes to smoking abstinence were used to measure leukotriene 4 (A) and 2,3-dinor-thromboxane B2 (B) by LC/MS-MS. Each individual data point represents subject-level measurements. p < 0.01 when comparing baseline with post-switching to abstinence (Day 7 and Day 14) for both Leukotriene 4 and 2,3-dinor-thromboxane B.