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

Connie S. Sosnoff, Kevin Caron, J. Ricky Akins, Kristin Dortch, Ronald E. Hunter, Brittany N. Pine, June Feng, Benjamin C. Blount, Yao Li, Dana M. Van Bemmel, Heather L. Kimmel, Kathryn C. Edwards, MacIej L. Goniewicz, Dorothy K. Hatsukami, B. Rey De Castro, John T. Bernert, Stephen Arnstein, Nicolette Borek, Ying Deng-Bryant, Elena MishinaCharles Lawrence, Andrew Hyland, Stephen S. Hecht, Kevin P. Conway, James L. Pirkle, Lanqing Wang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)736-744
Number of pages9
JournalNicotine and Tobacco Research
Issue number5
StatePublished - May 1 2022

Bibliographical note

Funding Information:
This work was supported by the National Institute on Drug Abuse at the National Institutes of Health and the Center for Tobacco Products at the U.S. Food and Drug Administration (FDA), under a contract to Westat (Contract No. HHSN271201100027C and HHSN271201600001C) and through an interagency agreement between the FDA Center for Tobacco Products and the CDC.

Publisher Copyright:
© 2021 Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2021.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.


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