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Do smokers have a different gingival crevicular fluid cytokine/chemokine profile than nonsmokers in clinically healthy periodontal sites? A systematic review and meta-analysis

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Abstract

Objectives

Assessing the evidence and comparing the levels of cytokines in gingival crevicular fluid (GCF) of periodontal healthy sites of smokers and nonsmokers.

Materials and methods

Seven databases were surveyed for observational studies up to April 8, 2021. Studies comparing cytokine levels on GCF in periodontally healthy sites of smokers vs. nonsmokers were included in the study. The risk of bias was evaluated using NIH (2014) tool. For meta-analyses, levels in GCF were analyzed, followed by evidence certainty assessment using the GRADE approach.

Results

Eighteen studies were included for qualitative evaluation, and eight were included in meta-analysis. Qualitatively, despite high heterogeneity and risk of bias observed among the studies, most of them presented no significant difference in the gingival crevicular cytokine fluid levels between groups. Regarding meta-analyses, interleukin-8 (IL-8) and superoxide dismutase (SOD) levels in GCF were analyzed. The significant difference was observed only in SOD levels, where heavy smokers had lower levels compared to nonsmokers (MD − 30.06 [− 40.17, − 19.96], p = 0.07, 95%CI), as well as light smokers had lower levels compared to nonsmokers (MD − 15.22 [− 16.05, − 14.39], p < 0.00001, 95%CI).

Conclusion

No distinct GCF cytokine profiles were detected for smokers and non-smokers. However, despite the limitations observed in the included studies, lower levels of SOD were identified in smokers.

Clinical relevance.

Indicating a distinct GCF profile of cytokines in periodontal healthy smokers may help to understand the mechanism whereby smoking may affect the host response.

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References

  1. World Health Organization. Tobacco (2021) https://www.who.int/health-topics/tobacco#tab=tab_1. Accessed 26 April 2021

  2. GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396 (10258):1223–1249. https://doi.org/10.1016/S0140-6736(20)30752-2.

  3. Chaffee BW, Couch ET, Vora MV, Holliday RS (2021) Oral and periodontal implications of tobacco and nicotine products. Periodontol 2000 87(1):241–253. https://doi.org/10.1111/prd.12395

    Article  PubMed  PubMed Central  Google Scholar 

  4. Nociti FH Jr, Casati MZ, Duarte PM (2015) Current perspective of the impact of smoking on the progression and treatment of periodontitis. Periodontol. 67(1):187–210. https://doi.org/10.1111/prd.12063

    Article  Google Scholar 

  5. Tonetti MS, Greenwell H, Kornman KS (2018) Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol 89(Suppl 1):S159–S172. https://doi.org/10.1002/JPER.18-0006.Erratum.In:JPeriodontol.2018Dec;89(12):1475

    Article  PubMed  Google Scholar 

  6. Pindborg JJ (1947) Tobacco and gingivitis: statistical examination of the significance of tobacco in the development of ulceromembranous gingivitis and in the formation of calculus. J Dent Res. 26(3):261–264. https://doi.org/10.1177/00220345470260030901

    Article  PubMed  Google Scholar 

  7. Buduneli N (2021) Environmental factors and periodontal microbiome. Periodontol 2000. 85(1):112–125. https://doi.org/10.1111/prd.12355

    Article  PubMed  Google Scholar 

  8. Leite FRM, Nascimento GG, Scheutz F, López R (2018) Effect of smoking on periodontitis: a systematic review and meta-regression. Am J Prev Med 54(6):831–841. https://doi.org/10.1016/j.amepre.2018.02.014

    Article  PubMed  Google Scholar 

  9. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS (2018) Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol 89(Suppl 1):S173–S182. https://doi.org/10.1002/JPER.17-0721

    Article  PubMed  Google Scholar 

  10. Chang J, Meng HW, Lalla E, Lee CT (2021) The impact of smoking on non-surgical periodontal therapy: A systematic review and meta-analysis. J Clin Periodontol 48(1):60–75. https://doi.org/10.1111/jcpe.13384

    Article  PubMed  Google Scholar 

  11. Kumar PS (2020) Interventions to prevent periodontal disease in tobacco-, alcohol-, and drug-dependent individuals. Periodontol 2000 84(1):84–101. https://doi.org/10.1111/prd.12333

    Article  PubMed  Google Scholar 

  12. Scannapieco FA, Gershovich E (2020) The prevention of periodontal disease-an overview. Periodontol 2000. 84(1):9–13. https://doi.org/10.1111/prd.12330

    Article  PubMed  Google Scholar 

  13. Haffajee AD, Socransky SS (2001) Relationship of cigarette smoking to the subgingival microbiota. J Clin Periodontol 28:377–388

    Article  Google Scholar 

  14. Johnson GK, Guthmiller JM (2000) The impact of cigarette smoking on periodontal disease and treatment. Periodontol 2007(44):178–194. https://doi.org/10.1111/j.1600-0757.2007.00212.x (PMID: 17474933)

    Article  Google Scholar 

  15. Al Kawas S, Al-Marzooq F, Rahman B, Shearston JA, Saad H, Benzina D, Weitzman M (2021) The impact of smoking different tobacco types on the subgingival microbiome and periodontal health: a pilot study. Sci Rep 11(1):1113. https://doi.org/10.1038/s41598-020-80937-3

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bostrom L. Linder LE. Bergstrotn J: Clinical expression of TNF-a in smoking associated periodontal disease. J din Periodontol 1998: 25: 767–773. © Munksgaard, 1998

  17. Bostro¨m L, Linder LE, Bergstro¨m J: Smoking and crevicular fluid levels of IL-6 and TNF-a in periodontal disease. J Clin Periodontol 1999; 26: 352–357. C Munksgaard, 1999

  18. Giannopoulou C, Kamma JJ, Mombelli A (2003) Effect of inflammation, smoking and stress on gingival crevicular fluidcytokine level. J Clin Periodontol 30:145–153. https://doi.org/10.1034/j.1600-051x.2003.300201.x

    Article  PubMed  Google Scholar 

  19. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 29(372):n71. https://doi.org/10.1136/bmj.n71

    Article  Google Scholar 

  20. Ryan R, Hills S (2016) How to GRADE the quality of the evidence. Cochrane Consumers and Communication Group. Available from: https://cccrg.cochrane.org/author-resources [Accessibility verified at April 2021]

  21. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A (2016) Rayyan — a web and mobile app for systematic reviews. Syst Rev 5:210. https://doi.org/10.1186/s13643-016-0384-4

    Article  PubMed  PubMed Central  Google Scholar 

  22. National Institutes of Health (2014) Quality assessment tool for observational cohort and cross-sectional studies. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Acessed 10 March 2021.

  23. GRADEpro GDT: GRADEpro guideline development tool [Software]. McMaster University, 2020 (developed by Evidence Prime, Inc.). Available from gradepro.org

  24. Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from guidelinedevelopment.org/handbook

  25. Balshem H et al (2011) GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 64:401–406

    Article  Google Scholar 

  26. Ramesh KSV, Swetha P, Mohan Kumar P, Sruthima NVS., Naresh Kumar C. Estimation of superoxide dismutase levels in saliva and gingival crevicular fluid among smokers and non-smokers in periodontitis patients - an observational study. Niger Med J. 2019;60(3):133–137. https://doi.org/10.4103/nmj.NMJ_56_19.

  27. Patel RP, Amirisetty R, Kalakonda B, Penumatsa NV, Koppolu P (2018) Influence of smoking on gingival crevicular fluid interleukin 1β and interleukin-8 in patients with severe chronic periodontitis among a rural population in India. Niger Med J. 59(4):33–38. https://doi.org/10.4103/nmj.NMJ_142_17

    Article  PubMed  PubMed Central  Google Scholar 

  28. Eren G, Türkoğlu HO, Atmaca H, Atilla FG (2015) Evaluation of GCF MMP-1, MMP-8, TGF-β1, PDGF-AB, and VEGF levels in periodontally healthy smokers. Turk J Med Sci 45(4):850–856

    Article  Google Scholar 

  29. Lütfioğlu M, Aydoğdu A, Sakallioğlu EE, Alaçam H, Pamuk F (2016) Gingival crevicular fluid interleukin-8 and lipoxin A4 levels of smokers and nonsmokers with different periodontal status: a cross-sectional study. J Periodontal Res 51(4):471–480. https://doi.org/10.1111/jre.12324

    Article  PubMed  Google Scholar 

  30. Haytural O, Yaman D, Ural EC, Kantarci A, Demirel K (2015) Impact of periodontitis on chemokines in smokers. Clin Oral Investig 19(5):979–986. https://doi.org/10.1007/s00784-014-1314-2

    Article  PubMed  Google Scholar 

  31. Agnihotri Rupali, Pandurang Pratibha, Kamath Shobha U, Goyal Rahul, Ballal Suhas, Shanbhogue Ashwini Y, Kamath Ullas, Bhat GS, Bhat KM (2009) Association of cigarette smoking with superoxide dismutase enzyme levels in subjects with chronic periodontitis. J Periodontol 80(4):657–662. https://doi.org/10.1902/jop.2009.080545

    Article  PubMed  Google Scholar 

  32. Buduneli N, Buduneli E, Kardeşler L, Lappin D, Kinane DF (2005) Plasminogen activator system in smokers and non-smokers with and without periodontal disease. J Clin Periodontol 32(4):417–424. https://doi.org/10.1111/j.1600-051X.2005.00694.x

    Article  PubMed  Google Scholar 

  33. Persson LP, Bergström J, Gustafsson A, Âsman B (1999). Tobacco smoking and gingival neutrophil activity in young adults. , 26(1), 9–13. https://doi.org/10.1034/j.1600-051x.1999.260102.x

  34. Bozkurt FY, Yetkin Ay Z, Sütçü R, Delibaş N, Demirel R (2006) Gingival crevicular fluid leptin levels in periodontitis patients with long-term and heavy smoking. J Periodontol 77(4):634–640. https://doi.org/10.1902/jop.2006.050277

    Article  PubMed  Google Scholar 

  35. Gajendran PL, Parthasarathy H, Tadepalli A (2018) Comparative evaluation of cathepsin K levels in gingival crevicular fluid among smoking and nonsmoking patients with chronic periodontitis. Indian J Dent Res. 29(5):588–593. https://doi.org/10.4103/ijdr.IJDR_95_17

    Article  PubMed  Google Scholar 

  36. N Guruprasad C, R Pradeep A. Influence of smoking on interleukin-34 levels in gingival crevicular fluid and plasma in periodontal health and disease: a clinico-biochemical study. Bull Tokyo Dent Coll. 2018;59(4):247–255. https://doi.org/10.2209/tdcpublication.2017-0051

  37. Kamma JJ, Giannopoulou C, Vasdekis VG, Mombelli A (2004) Cytokine profile in gingival crevicular fluid of aggressive periodontitis: influence of smoking and stress. J Clin Periodontol 31(10):894–902. https://doi.org/10.1111/j.1600-051X.2004.00585.x

    Article  PubMed  Google Scholar 

  38. Sakallioğlu EE, Sakallioğlu U, Lütfioğlu M, Pamuk F, Kantarci A (2015) Vascular endothelial cadherin and vascular endothelial growth factor in periodontitis and smoking. Oral Dis 21(2):263–269. https://doi.org/10.1111/odi.12261

    Article  PubMed  Google Scholar 

  39. Seri M, D'Alessandro A, Seri S. The effect of cigarette smoking on vitamin C and vitamin E levels of gingival crevicular fluid. Boll Soc Ital Biol Sper. 199;75(3–4):21–25.

  40. Srinivasan, S.; Krishnan, V.; Sivakamasundari, I.; Cynthia, R.A.J.; Kavitha, J.; Lakshmisree, S. Estimation and comparison of the levels of elastase in saliva, GCF & serum of smokers and non-smokers with chronic periodontitis - a clinico-biochemical study. Journal of Global Pharma Technology. 2020.

  41. Yadav VS., Mir RA, Bhatia A, Yadav R, Shadang M, Chauhan SS, Dhingra K, Kharbanda OP, Yadav R, Garg R. Metallothionein levels in gingival crevicular fluid, saliva and serum of smokers and non-smokers with chronic periodontitis. J Periodontol. 2020. https://doi.org/10.1002/JPER.20-0314.

  42. Ye D, Gajendra S, Lawyer G, Jadeja N, Pishey D, Pathagunti S, Lyons J, Veazie P, Watson G, McIntosh S, Rahman I (2020) Inflammatory biomarkers and growth factors in saliva and gingival crevicular fluid of e-cigarette users, cigarette smokers, and dual smokers: a pilot study. J Periodontol 91(10):1274–1283. https://doi.org/10.1002/JPER.19-0457

    Article  PubMed  Google Scholar 

  43. Özdemir B, Özmeric N, Elgün S, Barış E (2016) Smoking and gingivitis: focus on inducible nitric oxide synthase, nitric oxide and basic fibroblast growth factor. J Periodontal Res 51(5):596–603. https://doi.org/10.1111/jre.12338

    Article  PubMed  Google Scholar 

  44. Pinto JR, Bosco AF, Okamoto T, Guerra JB, Piza IG (2002) Effects of nicotine on the healing of extraction sockets in rats. A histological study Braz Dent J 13:3–9

    PubMed  Google Scholar 

  45. Nociti FH Jr, Nogueira-Filho GR, Tramontina VA, Machado MA, Barros SP, Sallum EA, Sallum AW (2001) Histometric evaluation of the effect of nicotine administration on periodontal breakdown: an in vivo study. J Periodontal Res 36(6):361–366. https://doi.org/10.1034/j.1600-0765.2001.360603.x (PMID: 11762871)

    Article  PubMed  Google Scholar 

  46. Lagdive SS, Marawar PP, Byakod G, Lagdive SB. Evaluation and comparison of interleukin-8 (IL-8) level in gingival crevicular fluid in health and severity of periodontal disease: a clinico-biochemical study. Indian J Dent Res. 2013 Mar-Apr;24(2):188–92. doi: https://doi.org/10.4103/0970-9290.116675. PMID: 23965444.

  47. Akalin FA, Toklu E, Renda N (2005) Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls. J Clin Periodontol 32(3):238–243. https://doi.org/10.1111/j.1600-051X.2005.00669.x (PMID: 15766365)

    Article  PubMed  Google Scholar 

  48. Trombelli L, Tatakis DN, Scapoli C, Bottega S, Orlandini E, Tosi M. Modulation of clinical expression of plaque-induced gingivitis. II. Identification of "high-responder" and "low-responder" subjects. J Clin Periodontol. 2004 Apr;31(4):239–52. doi: https://doi.org/10.1111/j.1600-051x.2004.00478.x.

  49. Oliver RC, Holm-Pederen P, Löe H (1969) The correlation between clinical scoring, exudate measurements and microscopic evaluation of inflammation in the gingiva. J Periodontol 40(4):201–209. https://doi.org/10.1902/jop.1969.40.4.201

    Article  PubMed  Google Scholar 

  50. Scott AE, Milward M, Linden GJ, Matthews JB, Carlile MJ, Lundy FT, Naeeni MA, Martin SL, Walker B, Kinane D, Brock GR, Chapple ILC (2012) Mapping biological to clinical phenotypes during the development (21 days) and resolution (21 days) of experimental gingivitis. J Clin Periodontol 39:123–131. https://doi.org/10.1111/j.1600-051X.2011.01825.x

    Article  PubMed  Google Scholar 

  51. Rosa GM, Lucas GQ, Lucas ON (2000) Study of the crevicular fluid flow rate in smokers. Acta Odontol Latinoam 13(1):51–60 (PMID: 11885468)

    PubMed  Google Scholar 

  52. Apatzidou DA, Riggio MP, Kinane DF (2005) Impact of smoking on the clinical, microbiological and immunological parameters of adult patients with periodontitis. J Clin Periodontol 32:973–983. https://doi.org/10.1111/j.1600-051X.2005.00788.x

    Article  PubMed  Google Scholar 

  53. Hugoson A, Rolandsson M (2011) Periodontal disease in relation to smoking and the use of Swedish snus: epidemiological studies covering 20 years (1983–2003). J Clin Periodontol 38(9):809–816. https://doi.org/10.1111/j.1600-051X.2011.01749.x

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was funded by the São Paulo Research Foundation, grant number 2019/01522-7, and by the Latin American Oral Health Association. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES), financial code: 001. The authors thank Heloísa Maria Ceccoti (H.M.C) for her assistance in the search strategy development. The authors also would like to thank Dr. FY Bozkurt from the Faculty of Dentistry, Süleyman Demirel University, Isparta, Turkey, for providing additional information related to their articles. Their time and assistance are greatly appreciated.

Funding

This study was founded  by the São Paulo Research Foundation, grant number 2019/01522–7 and 2019/17238–6, by the Latin American Oral Health Association, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES), financial code: 001.

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TPD and CMS conceived and designed the study and contributed to data collection, data interpretation, and drafting, editing, and revising of the manuscript. BEN contributed to data collection, preparation of tables and figures, and drafting, editing, and revising of the manuscript. GAMV contributed to data interpretation, preparation of figures, and editing and revising of the manuscript. MBM contributed to editing and revising of the manuscript. LCM, EAS, and KGSR conceived and designed the study and contributed to data analysis, data interpretation, and drafting, editing, and revising of the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Tamires Pereira Dutra.

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Dutra, T.P., Sacramento, C.M., Nagay, B.E. et al. Do smokers have a different gingival crevicular fluid cytokine/chemokine profile than nonsmokers in clinically healthy periodontal sites? A systematic review and meta-analysis. Clin Oral Invest 26, 1183–1197 (2022). https://doi.org/10.1007/s00784-021-04267-y

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