title: The relationship between cotinine concentrations and inflammatory markers among highly secondhand smoke exposed non-smoking adolescents.
abstract: BACKGROUND
  Secondhand smoke (SHS) exposure is a risk factor of respiratory, cardiovascular and inflammatory diseases, however its association with inflammatory markers among highly SHS exposed adolescents has not yet been explored.
  
  
  METHODS
  Participants included in this study were a subset of 68 non-smoking adolescents, aged 12.5-17.5 from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, recruited from Crete Greece. Smoking and SHS exposure was assessed via serum cotinine concentrations. Cytokines (Interleukin-1β, 2, 4, 5 and 6, tumor necrosis factor-α, interferon-γ, tumor growth factor-β1), immunoglobulins IgG, IgA, IgM, complement factors C3, C4, high sensitivity C-reactive protein, and endothelial inflammatory markers [soluble E-selectin, soluble L-selectin, soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecules-1 (sVCAM-1)] were assessed. Inflammatory markers in the lower 25th percentile and upper 75th percentile groups of cotinine levels were compared and multivariate linear regression analysis was performed controlling for age, sex and BMI.
  
  
  RESULTS
  Cotinine concentrations were notably elevated (geometric mean 0.82ng/ml, 95%CI 0.62-1.07) in this study population. A significant decrease in IL-4 (130.09 vs. 25.77pg/ml, p=0.014) and IL-6 (19.52 vs. 5.52pg/ml, p=0.008) concentrations between the upper 75th percentile cotinine level group and lower 25th percentile cotinine level group was observed. In a multivariate linear regression analysis, cotinine concentrations had a weak inverse association with IL-4 and IL-6 (p=0.028 and p=0.06) which was not statistically significant when adjusted for multiple comparisons (modified Bonferroni, p>0.016). No differences in the other variables was noted.
  
  
  CONCLUSIONS
  Among highly SHS exposed adolescents, cotinine levels had weak inverse association with IL-4 and IL-6, which did not achieve statistical significance. However, our results potentially indicate an immunosuppressive role of SHS. Further research is warranted to explore this hypothesis.
authors.affiliation: Center for Global Tobacco Control, Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, USA. Electronic address: yum892@mail.harvard.edu.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: Center for Global Tobacco Control, Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, USA; Department of Social Medicine, University of Crete, Greece.
authors.forename: Constantine I
authors.initials: CI
authors.lastname: Vardavas
authors.affiliation: Department of Social Medicine, University of Crete, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Plada
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Spain; Unit for Nutrition Epidemiology, Department of Preventive Medicine, University of Málaga, Málaga, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Wärnberg
authors.affiliation: Immunonutrition Research Group, Instituto de Ciencia y Tecnología de los alimentos y Nutrición, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Gómez-Martinez
authors.affiliation: Centre of Toxicology Science and Research, University of Crete, Greece.
authors.forename: Manolis N
authors.initials: MN
authors.lastname: Tzatzarakis
authors.affiliation: Centre of Toxicology Science and Research, University of Crete, Greece.
authors.forename: Aristeidis M
authors.initials: AM
authors.lastname: Tsatsakis
authors.affiliation: Immunonutrition Research Group, Instituto de Ciencia y Tecnología de los alimentos y Nutrición, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Esperanza-Ligia
authors.initials: EL
authors.lastname: Díaz
authors.affiliation: Immunonutrition Research Group, Instituto de Ciencia y Tecnología de los alimentos y Nutrición, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Ascensión
authors.initials: A
authors.lastname: Marcos
authors.affiliation: Department of Social Medicine, University of Crete, Greece.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Kafatos
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D003367:Cotinine / Q000097:blood*; D004781:Environmental Exposure; D005260:Female; D006115:Greece; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D012907:Smoking; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D014028:Tobacco Smoke Pollution; D003367:Cotinine
keywords: Adolescent; Cotinine; HELENA study; Inflammatory marker; Secondhand smoke exposure