{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T18:49:54Z","timestamp":1778957394835,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Chronic exposure to tobacco smoke leads to chronic low-grade systemic inflammation; however, little is known about the dose-dependent toxic effect of objective tobacco smoking on systemic inflammation. We examined the dose-dependent toxic effect of cotinine-verified tobacco smoking on leukocyte count in a representative sample of Korean adults, including 8655 men and 10,432 women aged 19\u201365 years from the Korean National Health and Nutrition Examination Survey. The participants were categorized into five groups by the level of urine cotinine (Ucot) as follows: A non-smoker group (&lt;50.00 ng\/mL) and four quartile groups for smokers for both men and women. The odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific high leukocyte count (\u226575th percentile) were calculated across five groups of Ucot concentrations using multiple logistic regression analyses. The mean values of leukocyte count gradually increased according to the grade of Ucot concentration in both sexes. The ORs (95% CIs) for high leukocyte count in the 4th Ucot quartile concentrations versus the non-smokers were 4.09 (3.39\u20134.94) for men and 3.91 (2.82\u20135.41) for women after adjusting for confounding variables. The present study confirmed the dose-response toxic effect of tobacco smoking on chronic low-grade systemic inflammation.<\/jats:p>","DOI":"10.3390\/ijerph16030503","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:18:20Z","timestamp":1549941500000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Dose-Dependent Toxic Effect of Cotinine-Verified Tobacco Smoking on Systemic Inflammation in Apparently Healthy Men and Women: A Nationwide Population-Based Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Won-Jun","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul 06273, Korea"},{"name":"Department of Medicine, Graduate School, Yonsei University, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2666-4249","authenticated-orcid":false,"given":"Ji-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul 06273, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Ra","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul 06273, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-476X","authenticated-orcid":false,"given":"Yong-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul 06273, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1161\/CIRCULATIONAHA.115.017926","article-title":"Relation of smoking with total mortality and cardiovascular events among patients with diabetes: A meta-analysis and systematic review","volume":"132","author":"Pan","year":"2015","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1161\/hc0902.104353","article-title":"Inflammation and atherosclerosis","volume":"105","author":"Libby","year":"2002","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.amjhyper.2003.11.005","article-title":"Relationship between white blood cell count and incident hypertension","volume":"17","author":"Shankar","year":"2004","journal-title":"Am J. Hypertens."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.numecd.2008.02.003","article-title":"Elevated white blood cell count is associated with arterial stiffness","volume":"19","author":"Lee","year":"2009","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1093\/aje\/kwi326","article-title":"White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of koreans","volume":"162","author":"Jee","year":"2005","journal-title":"Am. J. Epidemiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1177\/0022034511421200","article-title":"Cigarette smoking and inflammation cellular and molecular mechanisms","volume":"91","author":"Lee","year":"2012","journal-title":"J. Dental Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/1465-9921-7-132","article-title":"Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells","volume":"7","author":"Kode","year":"2006","journal-title":"Respir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/S0002-9149(02)02284-1","article-title":"Relation between markers of systemic vascular inflammation and smoking in women","volume":"89","author":"Bermudez","year":"2002","journal-title":"Am. J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1093\/ije\/28.5.824","article-title":"Effects of husbands\u2019 smoking on the incidence of lung cancer in korean women","volume":"28","author":"Jee","year":"1999","journal-title":"Int. J. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1093\/eurheartj\/ehi183","article-title":"Associations between cigarette smoking, pipe\/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease","volume":"26","author":"Wannamethee","year":"2005","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/S0195-668X(03)00260-4","article-title":"Independent association of various smoking characteristics with markers of systemic inflammation in menresults from a representative sample of the general population (monica augsburg survey 1994\/95)","volume":"24","author":"Sund","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Park, M.B., Kim, C.-B., Nam, E.W., and Hong, K.S. (2014). Does South Korea have hidden female smokers: Discrepancies in smoking rates between self-reports and urinary cotinine level. BMC Women\u2019s Health, 14.","DOI":"10.1186\/s12905-014-0156-z"},{"key":"ref_13","first-page":"536","article-title":"Hidden female smokers in Asia: A comparison of self-reported with cotinine-verified smoking prevalence rates in representative national data from an Asian population","volume":"21","author":"Khang","year":"2011","journal-title":"Tob. Control"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1006\/pmed.1994.1005","article-title":"An evaluation of the relationship between self-report and biochemical measures of environmental tobacco smoke exposure","volume":"23","author":"Emmons","year":"1994","journal-title":"Prev. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"696","DOI":"10.2105\/AJPH.78.6.696","article-title":"Elimination of cotinine from body fluids: Implications for noninvasive measurement of tobacco smoke exposure","volume":"78","author":"Jarvis","year":"1988","journal-title":"Am. J. Public Health"},{"key":"ref_16","first-page":"5","article-title":"Dose-dependent effect of cotinine-verified tobacco smoking on serum immunoglobulin e levels in korean adult males","volume":"1","author":"Dong","year":"2017","journal-title":"Nicot. Tob. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jcin.2011.09.027","article-title":"Cigarette smoking is associated with a dose-response effect in clopidogrel-treated patients with diabetes mellitus and coronary artery disease: Results of a pharmacodynamic study","volume":"5","author":"Ueno","year":"2012","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.3109\/10826084.2014.912227","article-title":"Dose-related association between urinary cotinine-verified smoking status and dyslipidemia among Korean men: The 2008\u20132010 Korea national health and nutrition examination survey","volume":"49","author":"Nam","year":"2014","journal-title":"Subst. Use Misuse"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/ntr\/ntq237","article-title":"Comparison of urine cotinine and the tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (nnal) and their ratio to discriminate active from passive smoking","volume":"13","author":"Goniewicz","year":"2011","journal-title":"Nicot. Tob. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1080\/13547500701421341","article-title":"Estimation of urinary cotinine cut-off points distinguishing non-smokers, passive and active smokers","volume":"12","author":"Wardas","year":"2007","journal-title":"Biomarkers"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kim, S. (2016). Overview of cotinine cutoff values for smoking status classification. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13121236"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Benowitz, N.L., Jacob III, P., Ahijevych, K., Jarvis, M.J., Hall, S., LeHouezec, J., Hansson, A., Lichtenstein, E., Henningfield, J., and Tsoh, J. (2002). Biochemical verification of tobacco use and cessation. Nicot. Tob. Res., 4.","DOI":"10.1080\/14622200210123581"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1089\/met.2014.0124","article-title":"Association between cotinine-verified smoking status and metabolic syndrome: Analyses of Korean national health and nutrition examination surveys 2008\u20132010","volume":"13","author":"Kang","year":"2015","journal-title":"Metab. Syndr. Related Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6807","DOI":"10.7314\/APJCP.2013.14.11.6807","article-title":"Biochemically-verified smoking rate trends and factors associated with inaccurate self-reporting of smoking habits in Korean women","volume":"14","author":"Kang","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/BF00117476","article-title":"Exposure of nonsmoking women to environmental tobacco smoke: A 10-country collaborative study","volume":"1","author":"Riboli","year":"1990","journal-title":"Cancer Causes Control"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.2169\/internalmedicine.46.0136","article-title":"Association between cigarette smoking, white blood cell count, and metabolic syndrome as defined by the Japanese criteria","volume":"46","author":"Ishizaka","year":"2007","journal-title":"Int. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.arcmed.2004.02.001","article-title":"Smoking-induced leukocytosis can persist after cessation of smoking","volume":"35","author":"Kawada","year":"2004","journal-title":"Arch. Med. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/00039896.1973.10666241","article-title":"Smoking habits and the leukocyte count","volume":"26","author":"Friedman","year":"1973","journal-title":"Arch. Environ. Health: Int. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4082\/kjfm.2017.38.2.75","article-title":"Joint effect of cigarette smoking and body mass index on white blood cell count in Korean adults","volume":"38","author":"Cho","year":"2017","journal-title":"Korean J. Family Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1164\/ajrccm.155.5.9154890","article-title":"Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells","volume":"155","author":"Mio","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/14622200601080299","article-title":"Secondhand smoke exposure and c-reactive protein levels in youth","volume":"9","author":"Wilkinson","year":"2007","journal-title":"Nicot. Tob. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3109\/01902148.2015.1096315","article-title":"Interleukin-10 modulates pulmonary neutrophilic inflammation induced by cigarette smoke exposure","volume":"41","author":"Higaki","year":"2015","journal-title":"Exp. Lung Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/3\/503\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:31:12Z","timestamp":1760185872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/3\/503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,11]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["ijerph16030503"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16030503","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,11]]}}}