Serum Concentrations of Cotinine and Trans-3′-Hydroxycotinine in US Adults: Results From Wave 1 (2013–2014) of the Population Assessment of Tobacco and Health Study

Abstract

Introduction The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative cohort of tobacco product users and nonusers. The study’s main purpose is to obtain longitudinal epidemiologic data on tobacco use and exposure among the US population. Aims and Methods Nicotine biomarkers—cotinine (COT) and trans-3′-hydroxycotinine (HCT)—were measured in blood samples collected from adult daily tobacco users and nonusers during Wave 1 of the PATH Study (2013–2014; n = 5012; one sample per participant). Participants’ tobacco product use and exposure to secondhand smoke were categorized based on questionnaire responses. Nonusers were subdivided into never users and recent former users. Daily tobacco users were classified into seven tobacco product use categories: exclusive users of cigarette, smokeless tobacco, electronic cigarette, cigar, pipe, and hookah, as well as polyusers. We calculated sample-weighted geometric mean (GM) concentrations of cotinine, HCT, and the nicotine metabolite ratio (NMR) and evaluated their associations with tobacco use with adjustment for potential confounders. Results The GMs (95% confidence intervals) of COT and HCT concentrations for daily tobacco users were 196 (184 to 208) and 72.5 (67.8 to 77.4) ng/mL, and for nonusers they were 0.033 (0.028 to 0.037) and 0.021 (0.018 to 0.023) ng/mL. Exclusive smokeless tobacco users had the highest COT concentrations of all user groups examined. The GM NMR in daily users was 0.339 (95% confidence interval: 0.330 to 0.350). Conclusions These nationally representative estimates of serum nicotine biomarkers could be the basis for reference ranges characterizing nicotine exposure for daily tobacco users and nonusers in the US adult population. Implications This report summarizes the serum nicotine biomarker measurements in Wave 1 of the PATH Study. We are reporting the first estimates of HCT in serum for daily tobacco users and nonusers in the noninstitutionalized, civilian US adult population; the first nationally representative serum COT estimates for daily exclusive users of different tobacco products and daily polyusers; and the first nationally representative estimate of the serum NMR in daily tobacco users by age, race/ethnicity, and sex.

Differential Toxicity of Electronic Cigarette Aerosols Generated from Different Generations of Devices In Vitro and In Vivo

“…Each of these medications comes in different nicotine strengths, highlighting nicotine’s critical role in exposure. Cotinine levels offer a direct measurement of the nicotine absorbed by the body and can be detected in blood, saliva, and urine, providing flexibility in sampling methods. − Further, cotinine has a longer half-life than nicotine, approximately 16 h, meaning it remains in the body longer and thus provides a more accurate measure of nicotine exposure over time. , In some studies, traditional cigarette exposure was cigs/day or pack-year, while e-cig exposure was quantified in terms of puffs. − However, some other studies have noted that, due to recall bias or social factors, self-reports often do not align with true smoking prevalence . Consequently, cotinine has emerged as the biomarker of choice for optimizing the evaluation of cigarette exposure.…”

“…39−41 However, some other studies have noted that, due to recall bias or social factors, self-reports often do not align with true smoking prevalence. 42 Consequently, cotinine has emerged as the biomarker of choice for optimizing the evaluation of cigarette exposure. Therefore, using cotinine levels as an alternative method for defining exposure doses could lead to more accurate assessments of nicotine exposure.…”

Predicting nicotine metabolism across ancestries using genotypes

“…This could lead to the identification of NMR cut-points that could be used to guide subject specific treatment paths. Additionally, our prediction model could help improve the understanding of nicotine metabolism in large representative populations (e.g., Population Assessment of Tobacco and Health [ 51 ]). This could help inform proposed and actual regulatory thresholds for nicotine levels.…”

“…Assessment of Tobacco and Health [51]). This could help inform proposed and actual regulatory thresholds for nicotine levels.…”

The use of biomarkers to guide precision treatment for tobacco use

“…Importantly, the NMR captures both genetic (i.e., CYP2A6 genetic variation) [ 59 , 60 ] and non-genetic (e.g., sex, oral contraceptives, race/ethnicity, body mass index, and alcohol) [ 61 – 63 ] influences on nicotine clearance without the need for genetic testing and the associated concerns about privacy. Epidemiological data on NMR values among the US population are now available for reference [ 64 ]. Thus, the NMR represents a genetically-informed phenotypic biomarker of nicotine metabolism with several practical advantages for translation into clinical practice.…”