Oral Health Group
Feature

Calm the Raging “Cs”

November 15, 2021
by Jo-Anne Jones, President, RDH Connection Inc.


The “Cs” (or cytokines) are making headline news frequently. The most unfavourable outcomes in COVID-19 patients’ risk profile repeatedly directs our attention to an over-expression of immune response termed a “cytokine storm.”

Today’s global research focuses on further understanding the potential role of cytokine storms in dictating the severity of the SARS-CoV-2 viral infection. The presence of a cytokine storm was identified in research by Channappanavar et al. of highly pathogenic coronavirus outbreaks previously seen in SARS-CoV and MERS-CoV. The exaggerated cytokine response was associated with pulmonary inflammation, lung damage, and multiple organ infection.1

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What is a Cytokine?
A cytokine is a signaling messenger involved in both the immunologic and inflammatory response. Thus, cytokines have the capability of mediating and regulating both reactions. When our body experiences a transient condition, cytokines play a crucial role in immune response, recovery, and healing. A well-coordinated innate immune response is the first line of defense against viral infection. However, when a transient infection becomes chronic, our immune system is directed to continually release pro-inflammatory mediators or cytokines to a pathologically excessive level. The over-expression of these pro-inflammatory mediators wreaks havoc, turning an inward attack on the body itself.

IL-6 (Interleukin-6) is one of the key cytokines identified and confirmed as a target promoter of COVID severity. “What shocked us was the discovery of the protein’s devastating, life-threatening impact to patients once they’re hospitalized. One tiny inflammatory protein [IL-6] robbed them of their ability to breathe.”2 It appears that elevated IL-6 levels can predict respiratory complications in COVID-19 patients. This acquired knowledge presents an opportunity to guide treatment decision-making in patients with the related hyperinflammatory syndrome.3 Once IL-6 has been activated, a series of acute-phase proteins are secreted, further amplifying the inflammatory response. One of these proteins is C-reactive protein or CRP, produced by the liver.4 High levels of IL-6, followed by CRP (C-reactive protein), were highly predictive of the requirement for mechanical ventilation.

In addition, tumor necrosis factor-alpha (TNF-α) is an essential mediator of cytokine production, having a distinct role in both acute and chronic inflammatory responses. The presence of TNF-α can be found in saliva and gingival crevicular fluid (GCF) with increased concentrations in periodontitis associated with tissue destruction and immune response.5,6 Elevated levels of TNF-α were associated with COVID-19 severity.7

Why Should We Be Concerned?
Chronic inflammation is a silent killer, and periodontitis is the sixth most prevalent chronic inflammatory disease recognized globally. The most compelling research to emerge over the last eighteen months has connected poor oral health with an increased incidence of COVID-19 complications. Periodontitis was associated with a higher risk of COVID-19 severity, complications, ICU admission, and death.

A multi-national study (McGill, Madrid, and Qatar University) published in the Journal of Clinical Periodontology of over 500 subjects highlighted the importance of good oral health in preventing and managing COVID-19 complications. The study found that COVID-19 patients with periodontitis were 3.5 times more likely to be admitted to intensive care, 4.5 times more likely to need a ventilator, and almost nine times more likely to die than those without periodontal disease. “There is a very strong correlation between periodontitis and disease outcome,” stated Dr. Belinda Nicolau, study co-author, Faculty of Dentistry, McGill University.8

The identification of inflammatory mediators such as IL-6, CRP and TNF-α associated with periodontitis alert our profession to further understand the importance of oral health in today’s world. In addition, a bacterial co-infection became another predictive factor for COVID-19 critical illness significantly influencing the mortality rate. According to study results by Liu et al., 80% of COVID-19 patients admitted into the ICU present with extremely high bacterial loads.9 This was demonstrated by elevated neutrophils, which are customarily associated with a bacterial infection and a significantly lower count of lymphocytes. Lymphocytes are the primary defender against viral infection. Therefore, the combination of elevated neutrophils and reduced lymphocytes reflects functional exhaustion of lymphocytes due to a bacterial superinfection impacting the original viral infection.10,11 The microbial exchange of periodontal pathogens such as P. intermedia, F. nucleatum and P. gingivalis from the oral cavity to the lungs present an elevated risk.12,13

Herein lies the connection with COVID-19 susceptibility and severity. The burden of an ongoing inflammatory disease and migration of periodontopathic organisms impact an individual’s resistance to disease, healing and recovery.

What is Our Essential Role and Responsibility?
As a dental hygienist, we play a significant role in reducing inflammation and meeting the needs of today’s population. A two-pronged etiologic approach drives this; the first addresses the bacterial component of periodontitis, and the second addresses the host response. There is substantial evidence to support a significant lowering of bacterial load, serum IL-6 levels, and systemic inflammation following periodontal treatment. However, we need to go one step further.

Our most current guidelines based on a “Systematic Review and Meta-analysis on the Non-surgical Treatment of Chronic Periodontitis by Means of Scaling and Root Planing With or Without Adjuncts”14 was “in favor of” evidence supporting one clinical recommendation as an adjunct to scaling and root planing, and that was subantimicrobial-dose doxycycline.15 Although the grade of evidence in this meta-analysis was measured by clinical attachment gain primarily, subantimicrobial-dose doxycycline also has been scientifically proven to significantly reduce inflammatory mediators, C-reactive protein (CRP), and IL-6.16,17 The reduction of these inflammatory mediators is a critical component of our role and responsibility. Subantimicrobial-dose doxycycline, 20 mg twice daily for three to nine months, is recommended as an adjunct to periodontal therapy for those with chronic periodontitis.

Self-care measures need to focus on inflammation reduction as well. We understand the superiority of a power toothbrush versus a manual toothbrush, yet a segment of our client population is hesitant to make the leap. A chairside trial capability, provided by Philips Sonicare In-Office Trial Program and the Oral-B Test Drive Program, bridges the gap between an objective recommendation to an authentic, internally motivated, and more meaningful experience. Any enhancement to aid in helping our clients maintain periodontal stability between professional visits is time well spent.

And what about the supporting science? As dental professionals, we need to have the confidence to make recommendations that are truly evidence-based. A six-month in-vivo study was conducted to compare the effects of scaling and root planing, plus twice-daily toothbrushing, in a stage I/II periodontitis population. The objective of the research was to enable study participants to manage stage I/II periodontitis at home by comparing the effects of daily self-care with a manual toothbrush (MTB) on both plaque, and periodontal inflammation or a Philips Sonicare powered toothbrush, following scaling and root planing, up to six months.18 This was a randomized, parallel, single-blind clinical trial. Results demonstrated that the Philips Sonicare powered toothbrush offers significant benefits to patients managing stage I/II periodontitis at home:

  • At 4 months interview, 15X more subjects converted to “healthy gingival status”
  • At 20 weeks, gingival bleeding was reduced up to 106x better than the MTB
  • Up to 6 months, 93% of subjects had reduced bleeding by 20% or more
  • At 6 months, 90x more subjects had reduced their pocket depths
  • The conclusive results of the study supported the powered toothbrush was statistically and significantly more effective in reducing plaque and symptoms of periodontal inflammation, as evidenced by BOP and PPD compared to the use of the manual toothbrush

Interdental cleaning is of paramount importance. The historical recommendation of “string flossing” remains an industry gold standard; however, poor compliance and limited manual dexterity result in a small percentage of our population deriving any significant benefit over brushing alone. A literature search conducted by Ng E, et al., using PubMed, yielded 105 articles between 1974 and 2018 related to the efficacy of interdental cleaning aids.19

The literature search revealed that several studies support the efficacy of oral irrigators as compared with any other interdental devices. Of significant importance in our world today is the ability of oral irrigators to reduce inflammation by reducing pro-inflammatory cytokines in the gingival crevicular fluid (GCF) of patients with periodontitis.20,21

Early research by Cobb et al. confirmed the removal of subgingival biofilm up to 6 mm using oral irrigators, with concurring studies reporting subgingival penetration on average to be about half the pocket depth.22,23

Most of the later studies in the literature search used commercially available products like Waterpik and Philips Sonicare AirFloss. What’s new in the oral irrigator space? Philips Sonicare has recently launched the Power Flosser. The unique “quad stream” nozzle directed by pulse wave technology sends out an X-shaped water stream designed to cover more surface area for a faster, deeper clean versus manual floss. Clinical studies support a statistically significant reduction in gingival inflammation and bleeding compared to traditional means of flossing or the use of an interdental brush.24-26

What does all this mean to us, our clinical practice, and to our clients? Sustainable and predictable outcomes and a daily self-care regiment that will focus on inflammation reduction and support our clients between professional visits.

In Conclusion
Looking at the big picture, we have an opportunity to mitigate the risk of systemic disease by helping our clients attain oral health. We can contribute significantly to the calming of the “Cs”. Are we cleaning teeth or impacting lives? It’s our conscious choice every day.

Jo-Anne Jones is a Key Opinion Leader for several leading corporations within the dental industry, including Philips Oral Healthcare.

References: 

  1. Channappanavar R, Perlman S. Pathogenic human infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 39, 529–539 (2017).
  2. Molayem S, Pontes CC. The Mouth-COVID Connection.  IL-6 Levels in Periodontal Disease – Potential Role in COVID-19 Related Respiratory Complication.  Published online ahead of print July 30, 2020.  J Calif Dent Assoc.
  3. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, Klein M, Weinberger T. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4.
  4. Vatansever HS, Becer E. Relationship between IL-6 and COVID-19: to be considered during treatment. Future Virology 2020 15:12, 817-822
  5. Rossomando EF, White L. A novel method for the detection of TNF-alpha in gingival crevicular fluid. J Periodontol. 1993;64:445–9.
  6. Teles RP, Likhari V, Socransky SS, Haffajee AD. Salivary cytokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: A cross-sectional study. J Periodontal Res. 2009;44:411–7.
  7. Singh P, Gupta ND, Bey A, Khan S. Salivary TNF-alpha: A potential marker of periodontal destruction. J Indian Soc Periodontol. 2014;18(3):306-310.
  8. Marouf N, Cai W, Said KN, et al. Association between periodontitis and severity of COVID-19 infection: A case-control study. J Clin Periodontol. 2021;48(4):483-491.
  9. Liu J, Liu Y, Xiang P et al. Neutrophil to Lymphocyte Ratio Predicts Critical Illness Patients with 2019 Coronavirus Disease in the Early Stage. J Transl Med 2020; 18: 206.
  10. Chen T, Wu D, Chen H et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 368, m1091 (2020).
  11. Wang D, Hu B, Hu C et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 323, 1061–1069 (2020).
  12. Mathieu E, Escribano-Vazquez U, Descamps D, et al. Paradigms of lung microbiota functions in health and disease, particularly, in asthma. Front Physiol. 2018;9:1168.
  13. Scannapieco FA, Genco RJ. Association of periodontal infections with atherosclerotic and pulmonary diseases. J Periodontal Res. 1999;34(7):340–5.
  14. Smiley CJ, Tracy SL, Abt E, et al. Systematic review and meta-analysis on the non-surgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts.  JADA 146(7):508-524.  July 2015.
  15. Smiley CJ, Tracy SL, Abt E, et al. Evidence-based clinical practice guideline on the non-surgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. JADA 2015;146(7):525-535.
  16. Brown DL, Desai KK, Vakili BA, et al. Clinical and Biochemical Results of the Metalloproteinase Inhibition with Subantimicrobial Doses of Doxycycline to Prevent Acute Coronary Syndromes (MIDAS) Pilot Trial.  Arterioscler Thromb Vasc Biol. 2004;24:733-738.
  17. Koppikar RS, Agrawal SV. The effect of sub-antimicrobial dose-doxycycline periodontal therapy on serum inflammatory biomarker C-reactive protein levels in post-menopausal Women: A 2-year, double-blinded, randomized clinical trial. Contemp Clin Dent. 2013;4(1):71-73.
  18. Milleman K, Milliman J, Starke M, et al. A comparison of the effects of scaling and root planing, plus twice-daily toothbrushing, in a stage I/II periodontitis population.   Salus Research Inc. Indiana, USA.  Study completed in 2020.
  19. Ng E, Lim LP. An Overview of Different Interdental Cleaning Aids and Their Effectiveness. Dent J (Basel). 2019;7(2):56.
  20. Cutler CW, Stanford TW, Abraham C, et al. Clinical benefits of oral irrigation for periodontitis are related to reduction of pro-inflammatory cytokine levels and plaque.  J Clin Periodontol. 2000 Feb; 27(2):134-43.
  21. Al-Mubarak S, Ciancio S, Aljada A, et al. Comparative evaluation of adjunctive oral irrigation in diabetics. J Clin Periodontol. 2002 Apr; 29(4):295-300.
  22. Cobb CM, Rodgers RL, Killoy WJ. Ultrastructural examination of human periodontal pockets following the use of an oral irrigation device in vivo. J Periodontol. 1988 Mar; 59(3):155-63.
  23. Eakle WS, Ford C, Boyd RL. Depth of penetration in periodontal pockets with oral irrigation.  J Clin Periodontol. 1986 Jan; 13(1):39-44.
  24. Milleman J, Milleman K, Wang P, et al. A study to assess the effects of adjunctive use of Philips Sonicare Power Flosser on plaque and gingival inflammation.   Data on file, 2019.
  25. Amini P, Imtiaz U, Li J, et al. A randomized, parallel study to compare Philips Sonicare Power Flosser and interdental brush on reducing gingival bleeding and plaque.  2020 Data on file.
  26. Gottenbos B, Suntjens W, Hotzl S. In-vitro biofilm removal from human enamel using a Philips Sonicare Power Flosser.  Philips Research Europe, 2019.

About the Author

An international, award-winning speaker, she has done over 1,000 presentations across Canada, the U.S., England, Ireland and Bermuda. Jo-Anne has been selected as one of DPR’s Top 25 Women in Dentistry and joins the 2021 Dentistry Today CE Leaders for the 11th consecutive year. A frank and open lecture style complemented by the provision of educational and clinical resources has earned Jo-Anne many loyal followers both nationally and internationally. To contact Jo-Anne, email at jjones@jo-annejones.com


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