Oral Health Group
Feature

Oral Inflammatory Load – A New Concept For The Understanding of Oral Disease

October 1, 2014
by Dr. Hendrik Doering, Dr. Howard C. Tenenbaum, Dr. Michael Glogauer


PERIODONTAL DIAGNOSIS AND ORAL INFLAMMATORY LOAD
In the process of diagnosis of periodontal disease, the primary goals are to establish the presence or absence of the disease, particularly active disease as well as its severity. An accurate diagnosis is also essential so as to allow the clinician to prognosticate on the risk of disease progression in the future. The traditional clinical periodontal examination includes the assessment of already existing damage to periodontal tissues as well as measures of periodontal inflammation (e.g. bleeding). It is a cost-effective and easy-to-use method in determining the location and severity of diseased periodontal tissues. However, in predicting future periodontal breakdown or even just quantifying current disease activity-especially inflammation, these methods are far from ideal.

With the involvement of dentistry as a part of the medical community, it is important to speak a common language. Therefore, in our understanding, it is a crucial part of our profession to set diagnostic standards that are understood between and within disciplines as well as on the interprofessional platform with other health care providers.

Advertisement






Therefore we want to introduce the concept of Oral Inflammatory Load (OIL), as a reproducible highly standardized value for the characterization and diagnosis of oral diseases. We propose OIL as a future diagnostic marker for the research that investigates the correlation of oral and non-oral diseases. This is based on the fact that OIL and not pocket depths, or periodontal pathogenic bacteria that explain the linkages found so far with systemic disease, cardiovascular disease to name but one. Otherwise how would one explain similar linkages between rheumatoid arthritis (a disease that is decidedly unrelated to infection with periodontal pathogens) and cardiovascular disease? To quantify oral inflammation and determine OIL we have developed an easy to administer an oral rinse test that can be used to measure the number of oral polymorphonuclear leukocytes (oral neutrophils, or oPMN), which are the key cells that play a role in the host inflammatory response and the OIL. In several peer-reviewed articles, we’ve shown, that there is a correlation between the amount of oPMNs and the severity of periodontal disease, which contributes to OIL. In fact we demonstrated that periodontal disease-associated OIL was reduced significantly once the disease was treated (Fig. 1).

FIGURE 1. oPMN counts for different groups of patients.


BACKGROUND OF THE CONCEPT
oPMNs are produced in the bone marrow from pluripotent stem cells from the myeloid lineage. The myeloid stem cells eventually give rise to neutrophils, basophils, eosinophils, and monocytes. A myeloid stem cell first differentiates into a myeloblast, and with several intermediate stages, after approximately two weeks of maturation, to a neutrophil. Approximately 1011 neutrophils are produced in the bone marrow of a healthy adult daily, and approximately 1012 in the presence of acute inflammation.1 The maturation of neutrophils and the other leukocytes is under the control of various factors (called cytokines) such as Interleukin-3, Colony Stimulating Factor and many more. The life in circulation of a mature neutrophil can be up to five days, and one to four days in the tissue.2 In order for a neutrophil to carry out its antimicrobial functions, it must first migrate to its eventual site of activity, typically a site of injury or infection. Upon arrival, in the case of the mouth, to a periodontal pocket (but could be a gingivitis site too), the neutrophils migrate through the extracellular matrix and constantly exit the tissues into the oral cavity. Hence, in the presence of inflammatory disease in the mouth (and we are using periodontal disease as the prime example), a vast amount of oPMNs are recruited and therefore the level oPMNs in the saliva of patients with active periodontal disease is increased dramatically and significantly in comparison to patients without periodontal disease or with controlled/inactive periodontal disease.3,4 The oral rinse assay developed in our laboratory can be used to assess for the levels of oPMN and hence, OIL.

CLINICAL RELEVANCE AND APPLICATION
Applying this concept for periodontitis, we believe that the focus should be on oral inflammation rather than on pocket depths since pockets are indicative of past disease but not current disease activity. In fact, given the current understanding of periodontal disease it would be surprising if oral inflammation correlated too closely with pocket depth readings or even bleeding on probing. We would like to present the concept that OIL is in fact the outcome parameter that needs to be quantified as a risk marker for non-oral diseases as opposed to focusing on specific oral diseases including but not limited to gingivitis, periodontitis and mucocutaneous diseases to name a few. Of course from a practical or clinical perspective, once elevated oral inflammation has been identified, it is then essential to make a diagnosis so that appropriate treatment can be rendered.

As noted above, in order to measure oral inflammation we have established an easy to administer oral rinse test that allows us to count the number of oPMN, which are the key cells in the host inflammatory response. In several peer-reviewed articles, we could show, that there is a correlation between the amount of oPMNs and the severity of periodontal disease.3-5 In fact we could also show, that a subsequent testing before and after treatment has an impact on the oral inflammatory load. (Fig. 1)

As a second goal in the ongoing establishment of this concept we developed a colourimetric test that allows for chair side screening for oral inflammation. It is well known that it is sometimes difficult to convince a patient that he or she might have periodontitis (particularly since it’s generally not painful). A positive colourimetric chair side test provides for the patient an objective indicator that they do indeed have oral inflammatory disease. Once shown such a test result it is more likely that a patient will accept the diagnosis and submit to treatment. Furthermore, the successful implementation of the test in the daily routine gives dental health care providers a cost-effective additional diagnostic aid for longitudinal maintenance of once established oral health. As soon as a positive test result is recorded, the appropriate steps can be rendered to initiate therapy for recurrent disease, which is even more important if routine clinical recall examination did not pick up disease-recurrence (Fig. 2). This of course ensures more favourable treatment outcomes over the longer term.

FIGURE 2. Different levels of oPMNs correlate with different results in our oral rinse test.

THE INCREASED IMPORTANCE OF PERIODONTAL DISEASE
We are shifting towards inflammation as the key risk indicator or even link between periodontitis and other non-oral conditions ranging from cardiovascular diseases to adverse pregnancy outcomes. Because periodont
al disease, the most common of the oral inflammatory conditions has several components, microbial in particular. There has been a clear focus on how periodontal pathogenic bacteria might play a causal role in the link between periodontitis and non-oral diseases, like cardiovascular disease or adverse pregnancy outcomes for example. Yet, as alluded to above, there are several diseases of inflammation where microbiological factors are absent including rheumatoid arthritis, and even osteoarthritis, but which also increase the risk for other non-oral conditions such as cardiovascular diseases, possibly through the effects of inflammation-associated increases in degradative enzymes that destroy an anti-inflammatory cardioprotective protein, fetuin.6-8 Hence, inflammation could be the key causal link between periodontal diseases and the other diseases noted here. Of course we do not suggest that the potential contribution of periodontal pathogenic bacteria to the linkages found between periodontitis and non-oral diseases should be ignored. But on examining of the literature relating to the correlation between diseases of inflammation (which do not have a microbial aetiology) and, for example, cardiovascular disease it is becoming increasingly clear that inflammation is a key element in the relationships between these disease entities and it is less likely related to the presence or absence of periodontal pathogenic bacteria. Hence, the ability to test for OIL is critically important in the search for mechanisms that might explain why oral inflammatory diseases have been linked statistically to non-oral conditions. Moreover, given the simplicity of the test developed for assessment of OIL, it will now be possible to carry out much larger studies using larger population sample sizes since the test does not need to be administered in a dental setting and could be administered in, for example, cardiologists’ offices for rapid assessment of OIL which would then allow us to determine with more certainty how and why periodontal or other oral inflammatory diseases are linked to non-oral diseases.

Within the structure of the emerging modern health care and the involvement of several professions for the overall treatment of dental patients we must understand that the future role of the dentist in the overall healthcare will become increasingly more important. We acknowledge and expect that the medical aspect of our profession will gain an increasing importance in the diagnosis and treatment of non-oral diseases that have a correlation with oral disease. Within this notion, and equally as important is a test for the assessment of the levels of oPMN. Such a simple-to-administer test can alert both the clinician and patient to the presence of oral disease in need of treatment in a manner previously not possible.


Dr. Hendrik Doering is a Resident in Periodontics at the Facutly of Dentistry, Univeristy of Toronto.

Dr. Tenenbaum is a Professor of Periodontology at the Faculty of Dentistry, and Professor of Laboratory Medicine and Pathogiology at the Faculty of Medicine, University of Toronto. He maintains a private practice in Periodontics at Mount Sinai Hospital.

Dr. Glogauer is a Professor at the University of Toronto and a Periodontist at OMGPerio in Hamilton. His research focuses on osteoimmunology and the impact of between the oral infection and systemic inflammation and disease. His research is funded by the Canadian Institutes of Health Research.

Oral Health welcomes this original article.

REFERENCES

1. Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol. 2010 Aug;31(8):318-24.

2. Pillay J, den Braber I, Vrisekoop N, Kwast LM, de Boer RJ, Borghans JA, et al. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood. 2010 Jul 29;116(4):625-7.

3. Bender JS, Thang H, Glogauer M. Novel rinse assay for the quantification of oral neutrophils and the monitoring of chronic periodontal disease. J Periodontal Res. 2006 Jun;41(3):214-20.

4. Landzberg M, Doering H, Aboodi GM, Tenenbaum HC, Glogauer M. Quantifying oral inflammatory load: oral neutrophil counts in periodontal health and disease. J Periodontal Res. 2014 Jul 14.

5. Huda S, Doering H, Tenenbaum H, Whittle W, Sigal M, Glogauer M. Oral Neutrophil Levels: A Screening Test for Oral Inflammatory Load in Pregnancy in a Medical Setting. J Periodontol. 2014;Under review.

6. Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010 Feb;69(2):325-31.

7. Schure R, Costa KD, Rezaei R, Lee W, Laschinger C, Tenenbaum HC, et al. Impact of matrix metalloproteinases on inhibition of mineralization by fetuin. J Periodontal Res. 2013 Jun;48(3):357-66.

8. Wong M, Toh L, Wilson A, Rowley K, Karschimkus C, Prior D, et al. Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation. Arthritis Rheum. 2003 Jan;48(1):81-9.