Document Type : Research articles

Author

Abstract

Background: There are many risk factors for childhood tinnitus such as hearing loss, exposure to high pitch sound, and passive smoking. Cotinine (C) is one of the metabolites of nicotine and is an important biochemical marker that reveals the objective and numerical indication of smoking exposure. Although there is a study investigating the role of urinary C levels in the etiology of tinnitus (T), the role of salivary C levels has not yet been elucidated.
Objectives: Therefore, this study aimed to investigate the risk factors of idiopathic subjective T in children in terms of passive smoking and whether the salivary C level can be used as a novel marker for monitoring and follow-up of T.
Methods: We retrospectively studied 1,245 children aged 7 - 15 years with T. We excluded 830 patients (66.5%) whose total tinnitus diagnosis was confirmed due to organic causes such as middle ear pathology and hearing loss. The remaining 415 (33.5%) patients with subjective T and 200 healthy individuals constituted the study and control groups. Complete blood counts, routine biochemical tests, and salivary C levels of children with T and controls were measured and their parents were also evaluated.
Results: In univariate analysis, parents C, childrens C, ALP, and erythrocyte levels were significantly associated with T (P < 0.001 in all). Regarding laboratory values, erythrocyte and serum ALP levels were significantly associated with T (P < 0.001 in both) in univariate analysis (OR, 0.99; 95% CI, 0.98 to 0.99 for erythrocyte and OR, 157.04; 95% CI, 44.7 to 551.6 for serum ALP level). No significant relationships were found between other parameters. These four parameters that were found to be significant in the univariate analysis showed meaningful associations with T in multivariate analysis (P < 0.01 for parents C and P < 0.001 for other parameters). It was also observed that as the C levels increased in the parents, the C level also increased in children.
Conclusions: There is a significant correlation between salivary C levels and parental salivary C levels in children. This suggests that the salivary C be used for evaluating the etiology of T in children and monitoring children with T exposed to cigarette smoke.

Keywords

  1. Baguley D, McFerran D, Hall D. Tinnitus. Lancet. 2013;382(9904):1600-7. doi: 10.1016/S0140-6736(13)60142-7. [PubMed: 23827090].
  2. Smith H, Fackrell K, Kennedy V, Barry J, Partridge L, Hoare DJ. A scoping review to catalogue tinnitus problems in children. Int J Pediatr Otorhinolaryngol. 2019;122:141-51. doi: 10.1016/j.ijporl.2019.04.006. [PubMed: 31029948].
  3. Jastreboff PJ, Gray WC, Mattox DE. Tinnitus and hyperacusis. In: Cummings CW, editor. Otolaryngology head and neck surgery. 3rd ed. New York: Mosby; 1998. p. 3198-222.
  4. Savastano M, Marioni G, de Filippis C. Tinnitus in children without hearing impairment. Int J Pediatric Otorhinolaryngol. 2009;73:S13-5. doi: 10.1016/s0165-5876(09)70003-5.
  5. Rosing SN, Schmidt JH, Wedderkopp N, Baguley DM. Prevalence of tinnitus and hyperacusis in children and adolescents: A systematic review. BMJ Open. 2016;6(6). e010596. doi: 10.1136/bmjopen-2015-010596. [PubMed: 27259524]. [PubMed Central: PMC4893873].
  6. Coelho CB, Sanchez TG, Tyler RS. Tinnitus in children and associated risk factors. Prog Brain Res. 2007;166:179-91. doi: 10.1016/S0079-6123(07)66016-6. [PubMed: 17956782].
  7. Veile A, Zimmermann H, Lorenz E, Becher H. Is smoking a risk factor for tinnitus? A systematic review, meta-analysis and estimation of the population attributable risk in Germany. BMJ Open. 2018;8(2). e016589. doi: 10.1136/bmjopen-2017-016589. [PubMed: 29472253]. [PubMed Central: PMC5855477].
  8. Noell CA, Meyerhoff WL. Tinnitus. Diagnosis and treatment of this elusive symptom. Geriatrics. 2003;58(2):28-34. [PubMed: 12596495].
  9. Shulman A. Epidemiolgy of tinnitus. In: Vernon JA, Moller AR, editors. Tinnitus diagnosis and treatment. Philadelphia: Lea and Febiger Press; 1991. p. 237-45.
  10. Lee DY, Kim YH. Urine cotinine should be involved in initial evaluation of tinnitus in adolescents. Clin Exp Otorhinolaryngol. 2018;11(4):242-9. doi: 10.21053/ceo.2017.01641. [PubMed: 29631390]. [PubMed Central: PMC6222183].
  11. Brunnberg E, Linden-Bostrom M, Berglund M. Tinnitus and hearing loss in 15-16-year-old students: Mental health symptoms, substance use, and exposure in school. Int J Audiol. 2008;47(11):688-94. doi: 10.1080/14992020802233915. [PubMed: 19031227].
  12. Thomson G, Wilson N, Howden-Chapman P. Population level policy options for increasing the prevalence of smokefree homes. J Epidemiol Community Health. 2006;60(4):298-304. doi: 10.1136/jech.2005.038091. [PubMed: 16537345]. [PubMed Central: PMC2577370].
  13. Hukkanen J, Jacob P3, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57(1):79-115. doi: 10.1124/pr.57.1.3. [PubMed: 15734728].
  14. Wall MA, Johnson J, Jacob P, Benowitz NL. Cotinine in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers. Am J Public Health. 1988;78(6):699-701. doi: 10.2105/ajph.78.6.699. [PubMed: 3369604]. [PubMed Central: PMC1350288].
  15. Ziegler UE, Kauczok J, Dietz UA, Reith HB, Schmidt K. Clinical correlation between the consumption of nicotine and cotinine concentrations in urine and serum by competitive enzyme-linked immunosorbent assay. Pharmacology. 2004;72(4):254-9. doi: 10.1159/000080381. [PubMed: 15539886].
  16. Binnie V, McHugh S, Macpherson L, Borland B, Moir K, Malik K. The validation of self-reported smoking status by analysing cotinine levels in stimulated and unstimulated saliva, serum and urine. Oral Dis. 2004;10(5):287-93. doi: 10.1111/j.1601-0825.2004.01018.x. [PubMed: 15315646].
  17. Kuo HW, Yang JS, Chiu MC. Determination of urinary and salivary cotinine using gas and liquid chromatography and enzyme-linked immunosorbent assay. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;768(2):297-303. doi: 10.1016/s1570-0232(01)00613-4. [PubMed: 11888058].
  18. Walker LM, Preston MR, Magnay JL, Thomas PB, El Haj AJ. Nicotinic regulation of c-fos and osteopontin expression in human-derived osteoblast-like cells and human trabecular bone organ culture. Bone. 2001;28(6):603-8. doi: 10.1016/s8756-3282(01)00427-6. [PubMed: 11425648].
  19. Fang MA, Frost PJ, Iida-Klein A, Hahn TJ. Effects of nicotine on cellular function in UMR 106-01 osteoblast-like cells. Bone. 1991;12(4):283-6. doi: 10.1016/8756-3282(91)90077-v. [PubMed: 1793680].
  20. Park B, Choi HG, Lee HJ, An SY, Kim SW, Lee JS, et al. Analysis of the prevalence of and risk factors for tinnitus in a young population. Otol Neurotol. 2014;35(7):1218-22. doi: 10.1097/MAO.0000000000000472. [PubMed: 24914798].
  21. Martines F, Sireci F, Cannizzaro E, Costanzo R, Martines E, Mucia M, et al. Clinical observations and risk factors for tinnitus in a Sicilian cohort. Eur Arch Otorhinolaryngol. 2015;272(10):2719-29. doi: 10.1007/s00405-014-3275-0. [PubMed: 25190254].
  22. Chang J, Ryou N, Jun HJ, Hwang SY, Song JJ, Chae SW. Effect of cigarette smoking and passive smoking on hearing impairment: Data from a population-based study. PLoS One. 2016;11(1). e0146608. doi: 10.1371/journal.pone.0146608. [PubMed: 26756932]. [PubMed Central: PMC4710530].
  23. Mahboubi H, Oliaei S, Kiumehr S, Dwabe S, Djalilian HR. The prevalence and characteristics of tinnitus in the youth population of the United States. Laryngoscope. 2013;123(8):2001-8. doi: 10.1002/lary.24015. [PubMed: 23606449].
  24. Yang S, Weiner BD, Zhang LS, Cho SJ, Bao S. Homeostatic plasticity drives tinnitus perception in an animal model. Proc Natl Acad Sci U S A. 2011;108(36):14974-9. doi: 10.1073/pnas.1107998108. [PubMed: 21896771]. [PubMed Central: PMC3169130].
  25. Langguth B. Treatment of tinnitus. Curr Opin Otolaryngol Head Neck Surg. 2015;23(5):361-8. doi: 10.1097/MOO.0000000000000185. [PubMed: 26261868].
  26. Torre P3, Dreisbach LE, Kopke R, Jackson R, Balough B. Risk factors for distortion product otoacoustic emissions in young men with normal hearing. J Am Acad Audiol. 2007;18(9):749-59. doi: 10.3766/jaaa.18.9.4. [PubMed: 18354884].
  27. Elgayar SA, Hussein OA, Abdel-Hafez AM, Thabet HS. Nicotine impact on the structure of adult male guinea pig auditory cortex. Exp Toxicol Pathol. 2016;68(2-3):167-79. doi: 10.1016/j.etp.2015.11.009. [PubMed: 26686587].
  28. Liang K, Poytress BS, Chen Y, Leslie FM, Weinberger NM, Metherate R. Neonatal nicotine exposure impairs nicotinic enhancement of central auditory processing and auditory learning in adult rats. Eur J Neurosci. 2006;24(3):857-66. doi: 10.1111/j.1460-9568.2006.04945.x. [PubMed: 16848798].
  29. Benowitz NL. Clinical pharmacology of nicotine: Implications for understanding, preventing, and treating tobacco addiction. Clin Pharmacol Ther. 2008;83(4):531-41. doi: 10.1038/clpt.2008.3. [PubMed: 18305452].
  30. Crinnion WJ. The CDC fourth national report on human exposure to environmental chemicals: What it tells us about our toxic burden and how it assist environmental medicine physicians. Altern Med Rev. 2010;15(2):101-9. [PubMed: 20806995].
  31. Jarvis MJ, 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. doi: 10.2105/ajph.77.11.1435. [PubMed: 3661797]. [PubMed Central: PMC1647100].
  32. Abrams DB, Follick MJ, Biener L, Carey KB, Hitti J. Saliva cotinine as a measure of smoking status in field settings. Am J Public Health. 1987;77(7):846-8. doi: 10.2105/ajph.77.7.846. [PubMed: 3592039]. [PubMed Central: PMC1647227].
  33. Jaakkola MS, Ma J, Yang G, Chin MF, Benowitz NL, Ceraso M, et al. Determinants of salivary cotinine concentrations in Chinese male smokers. Prev Med. 2003;36(3):282-90. doi: 10.1016/s0091-7435(02)00037-3. [PubMed: 12634019].
  34. Yamamoto Y, Nishida N, Tanaka M, Hayashi N, Matsuse R, Nakayama K, et al. Association between passive and active smoking evaluated by salivary cotinine and periodontitis. J Clin Periodontol. 2005;32(10):1041-6. doi: 10.1111/j.1600-051X.2005.00819.x. [PubMed: 16174266].
  35. Skorge TD, Eagan TM, Eide GE, Gulsvik A, Bakke PS. The adult incidence of asthma and respiratory symptoms by passive smoking in uterus or in childhood. Am J Respir Crit Care Med. 2005;172(1):61-6. doi: 10.1164/rccm.200409-1158OC. [PubMed: 15805186].
  36. Shiva F, Nasiri M, Sadeghi B, Padyab M. Effects of passive smoking on common respiratory symptoms in young children. Acta Paediatr. 2003;92(12):1394-7. doi: 10.1080/08035250310006638. [PubMed: 14971788].
  37. California Environmental Protection Acency. Health effects of exposure to environmental tobacco smoke. Final report. California Environmental Protection Acency Office of Environmental Health Hazard Assesment; 1997.
  38. Jiao ZX, Ao QL, Xiong M. Cigarette smoke extract inhibits the proliferation of alveolar epithelial cells and induces apoptosis. Sheng Li Xue Bao. 2006;58(3):244-54. [PubMed: 16786109].
  39. Levine AS, Sun L, Tan R, Gao Y, Yang L, Chen H, et al. The oxidative DNA damage response: A review of research undertaken with Tsinghua and Xiangya students at the University of Pittsburgh. Sci China Life Sci. 2017;60(10):1077-80. doi: 10.1007/s11427-017-9184-6. [PubMed: 29067646].
  40. Gencer M, Ceylan E, Aksoy N, Uzun K. Association of serum reactive oxygen metabolite levels with different histopathological types of lung cancer. Respiration. 2006;73(4):520-4. doi: 10.1159/000088895. [PubMed: 16432293].
  41. Lu L, Mackay DF, Newby DE, Pell JP. Association between salivary cotinine and cardiovascular biomarkers among nonsmokers and current smokers: Cross-sectional study of 10,081 participants. Eur J Vasc Endovasc Surg. 2014;48(6):703-10. doi: 10.1016/j.ejvs.2014.09.008. [PubMed: 25454789].