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

Overview

Journal Nicotine Tob Res

Publisher Oxford University Press

Specialty Public Health

Date 2021 Dec 13

PMID 34897512

Citations 7

Authors

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 Mishina

Charles Lawrence

Andrew Hyland

Stephen S Hecht

Kevin P Conway

James L Pirkle

Lanqing Wang

Affiliations

Soon will be listed here.

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.

Citing Articles

Association between the serum cotinine and trabecular bone score in the adult population: A cross-sectional study.

Bao S, Jimu W, Mu N, Yan F, Xing S, Zhou Z Tob Induc Dis. 2024; 22.

PMID: 39610648 PMC: 11603413. DOI: 10.18332/tid/194680.

Serum hydroxycotinine was associated with chronic kidney disease (CKD): a cross-sectional study based on NHANES.

Zhu M, Bi Z, Wang Y, Li W Ren Fail. 2024; 46(1):2356024.

PMID: 38832473 PMC: 11151805. DOI: 10.1080/0886022X.2024.2356024.

Nicotine and Cardiovascular Health: When Poison is Addictive - a WHF Policy Brief.

Dorotheo E, Arora M, Banerjee A, Bianco E, Cheah N, Dalmau R Glob Heart. 2024; 19(1):14.

PMID: 38312998 PMC: 10836189. DOI: 10.5334/gh.1292.

Differential Toxicity of Electronic Cigarette Aerosols Generated from Different Generations of Devices and .

Ma T, Chen H, Liao Y, Li J, Wang X, Li L Environ Health (Wash). 2023; 1(5):315-323.

PMID: 38028320 PMC: 10660664. DOI: 10.1021/envhealth.3c00099.

The use of biomarkers to guide precision treatment for tobacco use.

Siegel S, Tindle H, Bergen A, Tyndale R, Schnoll R Addict Neurosci. 2023; 6.

PMID: 37089247 PMC: 10121195. DOI: 10.1016/j.addicn.2023.100076.

References

Byrd G, Chang K, Greene J, deBethizy J . Evidence for urinary excretion of glucuronide conjugates of nicotine, cotinine, and trans-3'-hydroxycotinine in smokers. Drug Metab Dispos. 1992; 20(2):192-7. View

Bernert Jr J, McGuffey J, Morrison M, Pirkle J . Comparison of serum and salivary cotinine measurements by a sensitive high-performance liquid chromatography-tandem mass spectrometry method as an indicator of exposure to tobacco smoke among smokers and nonsmokers. J Anal Toxicol. 2000; 24(5):333-9. DOI: 10.1093/jat/24.5.333. View

Caraballo R, Giovino G, Pechacek T, Mowery P, Richter P, Strauss W . Racial and ethnic differences in serum cotinine levels of cigarette smokers: Third National Health and Nutrition Examination Survey, 1988-1991. JAMA. 1998; 280(2):135-9. DOI: 10.1001/jama.280.2.135. View

Shahab L, Goniewicz M, Blount B, Brown J, McNeill A, Alwis K . Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study. Ann Intern Med. 2017; 166(6):390-400. PMC: 5362067. DOI: 10.7326/M16-1107. View

Benowitz N . Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev. 1996; 18(2):188-204. DOI: 10.1093/oxfordjournals.epirev.a017925. View

Park M, Choi J . Differences between the effects of conventional cigarettes, e-cigarettes and dual product use on urine cotinine levels. Tob Induc Dis. 2019; 17:12. PMC: 6751982. DOI: 10.18332/tid/100527. View

Nakajima M, Yamamoto T, Nunoya K, Yokoi T, Nagashima K, Inoue K . Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes. J Pharmacol Exp Ther. 1996; 277(2):1010-5. View

Dempsey D, Tutka P, Jacob 3rd P, Allen F, Schoedel K, Tyndale R . Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin Pharmacol Ther. 2004; 76(1):64-72. DOI: 10.1016/j.clpt.2004.02.011. View

Jarvis M, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y . Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health. 1987; 77(11):1435-8. PMC: 1647100. DOI: 10.2105/ajph.77.11.1435. View

10.

Wagener T, Floyd E, Stepanov I, Driskill L, Frank S, Meier E . Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users. Tob Control. 2016; 26(e1):e23-e28. PMC: 5574194. DOI: 10.1136/tobaccocontrol-2016-053041. View

11.

Jarvis M, Giovino G, OConnor R, Kozlowski L, Bernert J . Variation in nicotine intake among U.S. cigarette smokers during the past 25 years: evidence from NHANES surveys. Nicotine Tob Res. 2014; 16(12):1620-8. DOI: 10.1093/ntr/ntu120. View

12.

Hukkanen J, Jacob 3rd P, Benowitz N . Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005; 57(1):79-115. DOI: 10.1124/pr.57.1.3. View

13.

Scherer G, Jarczyk L, Heller W, Biber A, Neurath G, Adlkofer F . Pharmacokinetics of nicotine, cotinine, and 3'-hydroxycotinine in cigarette smokers. Klin Wochenschr. 1988; 66 Suppl 11:5-11. View

14.

Roethig H, Munjal S, Feng S, Liang Q, Sarkar M, Walk R . Population estimates for biomarkers of exposure to cigarette smoke in adult U.S. cigarette smokers. Nicotine Tob Res. 2009; 11(10):1216-25. DOI: 10.1093/ntr/ntp126. View

15.

Goney G, Cok I, Tamer U, Burgaz S, Sengezer T . Urinary cotinine levels of electronic cigarette (e-cigarette) users. Toxicol Mech Methods. 2016; 26(6):414-8. DOI: 10.3109/15376516.2016.1144127. View

16.

Pirkle J, Bernert J, Caudill S, Sosnoff C, Pechacek T . Trends in the exposure of nonsmokers in the U.S. population to secondhand smoke: 1988-2002. Environ Health Perspect. 2006; 114(6):853-8. PMC: 1480505. DOI: 10.1289/ehp.8850. View

17.

Goniewicz M, Smith D, Edwards K, Blount B, Caldwell K, Feng J . Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes. JAMA Netw Open. 2019; 1(8):e185937. PMC: 6324349. DOI: 10.1001/jamanetworkopen.2018.5937. View

18.

Benowitz N, Jacob 3rd P . Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther. 1994; 56(5):483-93. DOI: 10.1038/clpt.1994.169. View

19.

Caudill S, Schleicher R, Pirkle J . Multi-rule quality control for the age-related eye disease study. Stat Med. 2008; 27(20):4094-106. DOI: 10.1002/sim.3222. View

20.

Johnstone E, Benowitz N, Cargill A, Jacob R, Hinks L, Day I . Determinants of the rate of nicotine metabolism and effects on smoking behavior. Clin Pharmacol Ther. 2006; 80(4):319-30. DOI: 10.1016/j.clpt.2006.06.011. View