Comparison of Nicotine Dependence and Biomarker Levels among Traditional Cigarette, Heat-Not-Burn Cigarette, and Liquid E-Cigarette Users: Results from the Think Study

Int J Environ Res Public Health. 2021 Apr 29;18(9):4777. doi: 10.3390/ijerph18094777.


This study aimed to compare Korean smokers' smoking-related biomarker levels by tobacco product type, including heat-not-burn cigarettes (HNBC), liquid e-cigarettes (EC), and traditional cigarettes (TC). Nicotine dependence levels were evaluated in Korean adult study participants including TC-, EC-, HNBC-only users and nonsmokers (n = 1586) from March 2019 to July 2019 in Seoul and Cheonan/Asan South Korea using the Fagerström Test Score. Additionally, urine samples (n = 832) were collected for the measurement of urinary nicotine, cotinine, OH-cotinine, NNAL(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), CYMA(N-acetyl-S-(2-cyanoehtyl)-L-cysteine), or CEMA (2-cyanoethylmercapturic acid) using LC-MS/MS. The median(interquartile range) nicotine dependence level was not different among the three types of smokers, being 3.0 (2.0-5.0) for TC- (n = 726), 3.0 (1.0-4.0) for EC- (n = 316), and 3.0 (2.0-4.0) for HNBC- (n = 377) only users. HNBC-only users presented similar biomarker levels compared to TC-only users, except for NNAL (HNBC: 14.5 (4.0-58.8) pg/mL, TC: 32.0 (4.0-69.6) pg/mL; p = 0.0106) and CEMA (HNBC: 60.4 (10.0-232.0) ng/mL, TC: 166.1 (25.3-532.1) ng/mL; p = 0.0007). TC and HNBC users showed increased urinary cotinine levels as early as the time after the first smoke of the day. EC users' biomarker levels were possibly lower than TC or HNBC users' but higher than those of non-smokers.

Keywords: biomarker; electronic cigarette; heat-not-burn cigarette; nicotine dependence; smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Chromatography, Liquid
  • Cotinine
  • Electronic Nicotine Delivery Systems*
  • Hot Temperature
  • Humans
  • Republic of Korea
  • Seoul
  • Tandem Mass Spectrometry
  • Tobacco Products*
  • Tobacco Use Disorder*


  • Biomarkers
  • Cotinine