Abstract
The objective of this study was to assess the utility of urinary Clara cell protein (CC16) as a biomarker of increased lung epithelial permeability in non-smokers exposed to outdoor secondhand smoke. Twenty-eight healthy non-smoking adults visited outdoor patios of a restaurant and a bar where non-participants smoked and an open-air control with no smokers on three weekend days in a crossover study; subjects visited each site once for 3 h. Urine samples were collected at baseline, immediately post exposure and next morning, and analyzed for CC16. Changes in CC16 across location types or with cigarette count were analyzed using mixed-effect models, which included all subjects and stratified by gender. Urinary CC16 was higher in males (n=9) compared with females (n=18) at all measurement occasions (P<0.002), possibly reflecting prostatic contamination. Urinary CC16 from pre-exposure to post-exposure was higher following visits to restaurant and bar sites compared with the control among females but this increase did not reach statistical significance. Post-exposure to pre-exposure urinary CC16 ratios among females increased with cigarette count (P=0.048). Exposure-related increases in urinary CC16 were not seen among males. In conclusion, urinary CC16 may be a useful biomarker of increased lung epithelial permeability among female non-smokers; further work will be required to evaluate its applicability to males.
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References
USDHHS. The health consequences of involuntary smoking: a report of the surgeon general. In: Services U.D.o.H.a.H. (Ed.). United States Public Health Service, Office on Smoking and Health, 1986.
Vineis P., Hoek G., Krzyzanowski M., Vigna-Taglianti F., Veglia F., and Airoldi L., et al. Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study. Environ Health 2007: 6 (1): 7–13.
Barnoya J., and Glantz S.A. Cardiovascular effects of secondhand smoke—nearly as large as smoking. Circulation 2005: 111 (20): 2684–2698.
Flouris A.D., Metsios G.S., Carrillo A.E., Jamurtas A.Z., Gourgoulianis K., and Kiropoulos T., et al. Acute and short-term effects of secondhand smoke on lung function and cytokine production. Am J Respir Crit Care Med 2009: 179 (11): 1029–1033.
Flouris A.D., Vardavas C.I., Metsios G.S., Tsatsakis A.M., and Koutedakis Y. Biological evidence for the acute health effects of secondhand smoke exposure. Am J Physiol Lung Cell Mol Physiol 2009: 298 (1): L3–L12.
Bondy S.J., Zhang B., Kreiger N., Selby P., Benowitz N., and Travis H., et al. Impact of an indoor smoking ban on bar workers’ exposure to secondhand smoke. J Occup Environ Med 2009: 51 (5): 612–619.
Herman P.M., and Walsh M.E. Hospital admissions for acute myocardial infarction, angina, stroke, and asthma after implementation of Arizona's comprehensive statewide smoking ban. Am J Public Health 2010: 101 (3): 491–496.
Georgia Smoke-Free Air Act. 2005. SB 90/AP. 148th Georgia General Assembly, Regular Session. 9 May 2005. Available at: http://www1.legis.ga.gov/legis/2005_06/pdf/sb90.pdf (accessed 28 June 2012).
Athens-Clarke County, Georgia. Code of Ordinances, Section 4.3. 5 July 2005. Available: http://library.municode.com/index.aspx?clientId=12400&stateId=10&stateName=Georgia (accessed 28 June 2012)
St.Helen G., Hall D.B., Kudon L.H., Pearce J., Baptiste S., and Ferguson S., et al. Particulate matter (PM2.5) and carbon monoxide from secondhand smoke outside bars and restaurants in downtown Athens, Georgia. J Environ Health 2011: 74 (3): 8–11.
Kaufman P., Zhang B., Bondy S.J., Klepeis N., and Ferrence R. Not just ‘a few wisps’: real-time measurement of tobacco smoke at entrances to office buildings. Tob Control 2010: 20 (3): 212–218.
Klepeis N.E., Ott W.R., and Switzer P. Real-time measurement of outdoor tobacco smoke particles. J Air Waste Manage Assoc 2007: 57 (5): 522–534.
Hall J., Bernert J., Hall D., St Helen G., Kudon L., and Naeher L. Assessment of exposure to secondhand smoke at outdoor bars and family restaurants in athens, georgia, using salivary cotinine. J Occup Env Hyg 2009: 6 (11): 698–704.
Heiss C., Amabile N., Lee A.C., Real W.M., Schick S.F., and Lao D., et al. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function∷ sustained vascular injury and blunted nitric oxide production. J Am Coll Cardiol 2008: 51 (18): 1760–1771.
USDHHS (U.S. Department of Health and Human Services). The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Centers for Disease Control and Prevention, National Centers for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health: Atlanta, GA, 2006.
USEPA. Respiratory health effects of passive smoking: lung cancer and other disorders. U.S. Environmental Protection Agency: Washington D.C., 1992.
WHO. International Consultation on Environmental Tobacco Smoke (ETS) and Child Health, WHO: Geneva, Switzerland, 1974.
Hulka B.S. Epidemiological studies using biological markers: issues for epidemiologists. Cancer Epidemiol Biomarkers Prev 1991: 1 (1): 13–19.
Morrison D., Rahman I., Lannan S., and MacNee W. Epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers. Am J Respir Crit Care Med 1999: 159 (2): 473–479.
Olivera D.S., Boggs S.E., Beenhouwer C., Aden J., and Knall C. Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitro. Inhalation Toxicol 2007: 19 (1): 13–22.
Mason G., Uszler J., Effros R., and Reid E. Rapidly reversible alterations of pulmonary epithelial permeability induced by smoking. Chest 1983: 83 (1): 6–11.
Broeckaert F., Arsalane K., Hermans C., Bergamaschi E., Brustolin A., and Mutti A., et al. Serum Clara cell protein: a sensitive biomarker of increased lung epithelium permeability caused by ambient ozone. Environ Health Persp 2000: 108 (6): 533–537.
Broeckaert F., Clippe A., Knoops B., Hermans C., and Bernard A. Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Ann N Y Acad Sci 2000: 923 (1): 68–77.
Bernard A. Critical review of Clara cell protein: sound science? Biomarkers 2008: 13 (3): 237–243.
Hantson P., Bernard A., and Hermans C. Kinetics and determinants of the changes of CC16, a lung secretory protein in a rat model of toxic lung injury. Clin Toxicol 2008: 46 (3): 230–238.
Arjomandi M., Tager I.B., Bastaki M., Chen C., Holland N., and Balmes J.R. Is there an association between lifetime cumulative exposure and acute pulmonary responses to ozone? J Occup Environ Med 2008: 50 (3): 341–349.
Van Miert E., Dumont X., and Bernard A. CC16 as a marker of lung epithelial hyperpermeability in an acute model of rats exposed to mainstream cigarette smoke. Toxicol Lett 2005: 159 (2): 115–123.
St. Helen G., Bernert J.T., Hall D.B., Sosnoff C.S., Xia Y., and Balmes J.R., et al. Exposure to secondhand smoke outside of a bar and a restaurant leads to increases in tobacco exposure biomarkers in non-smokers. Environ Health Perspect 2012; http://dx.doi.org/10.1289/ehp.1104413 (in press).
Andersson L., Lundberg P.A., and Barregard L. Methodological aspects on measurement of Clara cell protein in urine as a biomarker for airway toxicity, compared with serum levels. J Appl Toxicol 2007: 27 (1): 60–66.
Poortmans J.R., Rampaer L., and Wolfs J.C. Renal protein excretion after exercise in man. Eur J Appl Physiol 1989: 58 (5): 476–480.
Benowitz N.L., Goniewicz M., Eisner M., Lazcano-Ponce E., Zielinska-Danch W., and Koszowski B., et al. Urine cotinine underestimates exposure to tobacco-derived lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in passive compared to active smokers. Cancer Epidemiol Biomarkers Prev 2010: 19 (11): 2795–2800.
Hukkanen J., Jacob P., and Benowitz N.L. Metabolism and disposition kinetics of nicotine. Pharmacol Rev 2005: 57 (1): 79–115.
Otsuka R., Watanabe H., Hirata K., Tokai K., Muro T., and Yoshiyama M., et al. Acute effects of passive smoking on the coronary circulation in healthy young adults. JAMA 2001: 286 (4): 436–441.
Bonetti P.O., Lardi E., Geissmann C., Kuhn M.U., Bruesch H., and Reinhart W.H. Effect of brief secondhand smoke exposure on endothelial function and circulating markers of inflammation. Atherosclerosis 2010: 215 (2011): 218–222.
Cameron M., Brennan E., Durkin S., Borland R., Travers M.J., and Hyland A., et al. Secondhand smoke exposure (PM2.5) in outdoor dining areas and its correlates. BMJ 2010: 19 (1): 19–23.
Eisner M.D., Katz P.P., Yelin E.H., Hammond S.K., and Blanc P.D. Measurement of environmental tobacco smoke exposure among adults with asthma. Environ Health Perspect 2001: 109 (8): 809–814.
Acknowledgements
We thank the 28 study participants as well as Anderson Morris who served as a technician and driver. Thanks also to Pam Olive, Cindy Phan and Veronica Dave for help with analysis of CC16 and urinary creatinine. We further acknowledge Connie Sosnoff and Yang Xia for salivary cotinine and urinary NNAL analyses. This study was funded by the National Institutes of Environmental Health Science, project number 1R21ES017845-01A1. Dr. John Balmes is funded in part by the Flight Attendant Medical Research Institute (FAMRI). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
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JRB was funded in part through a grant from the Flight Attendant Medical Research Institute (FAMRI) that awards competitive grants through requests for proposals, which can be initiated by the board of trustees of FAMRI. Once funded, FAMRI has no role in the design, conduct, interpretation, or publication of the research. The organization does not gain or lose financially through publication of any article. The other authors declare no conflict of interest.
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St Helen, G., Holland, N., Balmes, J. et al. Utility of urinary Clara cell protein (CC16) to demonstrate increased lung epithelial permeability in non-smokers exposed to outdoor secondhand smoke. J Expo Sci Environ Epidemiol 23, 183–189 (2013). https://doi.org/10.1038/jes.2012.68
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DOI: https://doi.org/10.1038/jes.2012.68