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«EVALUATION OF ORAL NEUTROPHIL LEVELS AS A QUANTITATIVE MEASURE OF PERIODONTAL INFLAMMATORY LOAD IN PATIENTS WITH SPECIAL NEEDS By Anita Moosani BSc, ...»

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The use of PMN quantification to assess periodontal disease status and responses to treatment was first proposed in 1978 (Raeste & Aura, 1978), an idea which seems useful when considering the effect of PMNs on periodontal tissues, and the fact that their levels are naturally elevated during disease (Attstrom, 1970; Schroeder, 1973), and are likely proportional to the extent of disease activity (Attstrom, 1970; Schiött & Löe, 1970).

A simple method for measurement of oral PMNs has been developed and involves the use of a non-invasive oral rinse assay. This was validated at the University of Toronto‟s Department of Periodontology in 2006, and demonstrates promise in allowing the clinician to monitor the activity and severity of periodontal disease as well as its progression (Bender, Thang, & Glogauer, 2006). However, the use of the oral rinse assay is impractical in patients who lack the cooperation and/or coordination required to reliably rinse and expectorate.

This research study will evaluate a novel technique for oral neutrophil quantification, using a PMN assay, as a quantitative measure of periodontal inflammatory load in uncooperative patients with special needs.

GOALS

1. To correlate oral neutrophil counts obtained by the PMN assay with conventional clinical parameters of periodontal health status in uncooperative patients with special

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2. To assess the feasibility of using the PMN assay to provide objective and quantitative data so that gingival inflammation can be quantified and monitored in uncooperative patients with special needs.

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Definitions and Prevalence of Disability Patients with special health care needs are defined as those with a, “physical, developmental, mental, sensory, behavioural, cognitive, or emotional impairment or limiting condition that requires medical management, health care intervention, and/or use of specialized services or programs” (American Academy of Pediatric Dentistry Council on Clinical Affairs [AAPD], 2011/12). Disabilities can be congenital or acquired, as well as either visible (i.e. physical), or invisible (e.g. mental). The International Classification of Functioning, Disability, and Health (ICF), defines disability as a broad term that looks at the interaction of health conditions, environmental, and personal factors on body functions, individual activities, and participation in society (World Health Organization [WHO], 2011). Developmental disability is defined as a mental or physical impairment with onset during the developmental period from birth to 22 years of age, and results in significant functional limitations in three or more areas of major life activities, such as self-care, language, mobility, or capacity for independent living (Accardo & Whitman, 2012). Approximately 1.85 million people or about 15% of the population in Ontario have a disability (Ontario Government, 2010), and disability is reported by about 4.4 million Canadians (14.3%; Government of Canada, 2010).

The World Health Organization estimates that over one billion people, or 15% of the world‟s population, have some form of disability (WHO, 2011).

Oral Health Care Needs for Patients with Special Needs Oral disease, including caries and periodontal disease, is significantly prevalent in the special needs population (Scott, March, & Stokes, 1998; Lopez del Valle, Waldman, & Perlman, 2007; Dellavia, Allievi, Pallavera, Rosati, & Sforza, 2009; Anders & Davis, 2010). Oral health is noted to be especially poor in patients who are unable to cooperate for routine dental care (Anders & Davis, 2010), due to movement disorders, cognitive problems or any number of disabilities. Data are limited regarding oral health care in patients with severe developmental delays. These patients need more supervision and are reliant on caregivers for their daily oral hygiene routine. Further, they are dependent on dentists who are comfortable in treating them despite their special needs, medical health complexity, and lack of cooperation (de Jongh, van Houtem, van der Schoof, Resida, & Broers, 2008).

Unfortunately, persons with disabilities experience significant disparities and unmet oral health care needs from dental professionals (Scott, March, & Stokes, 1998; Loeppky & Sigal, 2007; Sigal, 2009). Reasons cited for this disparity include lack of training in the dental curriculum leading to lack of familiarity with this population, belief that special equipment is required, lack of cooperation or communication leading to difficulty in diagnosis, increased time involvement for treatment, or lack of reimbursement for dental services provided through government programs (Fenton, Hood, Holder, May, & Mouradian, 2003; Loeppky & Sigal, 2007; Lopez del Valle, Waldman, & Perlman, 2007; Koneru & Sigal, 2009). The demands for oral health care are only going to increase in this population with the average lifespan increasing due to advances in medical care, and continued deinstitutionalization and integration of persons with special needs into the community (Scott, March, & Stokes, 1998;

Sigal, 2009). Thus, appropriate diagnosis and provision of dental treatment to adult patients that are uncooperative due to varying degrees of developmental delay is a persistent challenge in dentistry (Ananthanarayan, Sigal, & Godlewski, 1998).

The Mount Sinai Hospital Dental Program for Persons with Disabilities The Mount Sinai Hospital Dental Program for Persons with Disabilities, the largest of its kind in Canada, was established in 1975 and provides comprehensive oral health care to patients with special needs in a hospital setting (Sigal, 2010). Patients are referred by their family physician, dentist, case support worker, or allied institution. The hospital based program plays a vital role in providing dental care to patients who are unable to receive treatment in their local community. The overall need for this program is reflected by the current waiting list for dental treatment under GA, which is approximately twelve months following the initial consultation (Park & Sigal, 2008). The Program also serves to educate undergraduate and graduate students attending the University of Toronto‟s Faculty of Dentistry in conjunction with the Department of Paediatric Dentistry, to familiarize students with this population so that they are comfortable in treating patients with special needs in their future community practice (Sigal, 2010). Dental recall examinations for patients with special needs are provided by dental students supervised by staff, as well as hospital dental residents. Dental treatment is provided by hospital dental staff and residents in the ambulatory dental clinic as well as under GA in the operating room. However, despite attempts to manage behaviour in the clinical setting, many patients with special needs still require dental treatment under GA due to poor cooperation (Hennequin, Faulks, & Roux, 2000; Petrovic, Markovic, & Peric, 2011). The Mount Sinai Hospital Dental Clinic has provisions for uncooperative patients to have comprehensive dental care safely and predictably in one treatment session (Ananthanarayan, Sigal, & Godlewski, 1998), followed by de-sensitization to the dental clinic via subsequent dental recalls without sedation.





However, there are still important limitations related to examination, diagnosis, and treatment in this population that will be described later.

Classification of Periodontal Diseases Periodontal diseases are a group of inflammatory disorders that may be inherited or acquired, and are characterized by progressive destruction of the tissues that surround and support the teeth, known as the periodontium (Armitage, 1999). The periodontium is comprised of root cementum, the periodontal ligament, alveolar bone, and its overlying mucosa (Nanci & Bosshardt, 2006). The prevalence of periodontal diseases as reported in the literature varies between 14 to 65% depending on the definitions used and the population studied (Costa et al., 2009). The most common periodontal diseases are grouped under two broad categories of conditions, called gingivitis and periodontitis (Armitage, 1999).

Gingivitis is defined as inflammation of the gingiva associated with teeth that do not demonstrate attachment loss. Gingivitis is further divided into those conditions which are plaque-induced and those that are not (Armitage, 1999). „Plaque-induced‟ gingivitis is a consequence of the interaction between the pathogens within the dental plaque or biofilm at the tooth/gingival interface, and the host tissues and inflammatory cells within them (Armitage, 2004). This interaction between the plaque and host is influenced by local and epigenetic factors such as smoking and plaque, medical problems including but not limited to diseases such as diabetes mellitus, medications including anticonvulsants, immunosuppressants, oral contraceptives, and calcium channel blockers, and malnutrition (Armitage, 1999; Mariotti, 1999; Kinane & Marshall, 2001). „Non-plaque-induced‟ gingival conditions are caused by specific bacterial, viral, fungal, or genetic factors, or can imply the presence of an underlying medical condition (Armitage, 1999). Clinical signs of gingivitis include enlarged gingival contours due to edema or fibrosis, change in color (erythema), elevated sulcular temperature, bleeding on stimulation, and increased gingival exudate.

These signs are associated with stable attachment levels on a periodontium that may or may not be reduced (Mariotti, 1999). In gingivitis, inflammation is limited to the gingiva and may be reversed by removing the etiological factors (i.e. plaque; Löe, Theilade, & Jensen, 1965).

Persistent inflammation may have a role in the progression to periodontal attachment loss (Mariotti, 1999).

Periodontitis is a condition characterized by gingival inflammation of the periodontium, as with gingivitis, but is also associated with the irreversible destruction of connective tissue apical to the cemento-enamel junction, referred to as periodontal attachment loss (Ranney, 1991). Periodontitis is divided into other categories including chronic, aggressive, or as a manifestation of systemic (i.e. non-oral) disease. These categories are distinguished further based on the extent and severity of disease as follows. Chronic periodontitis can be localized (less than 30% of sites are involved), or generalized (more than 30% of sites are affected).

Severity is characterized by the amount of clinical attachment loss (CAL) as measured by a periodontal probe, as slight (1-2 mm CAL), moderate (3-4 mm CAL), or severe (≥ 5 mm CAL; Armitage, 1999). The primary etiological agent appears to be gram negative bacteria, though the exact spectrum of pathogens contained within the biofilm which initiates periodontitis is not firmly established. Moreover, it has been suggested that these suspected pathogenic bacteria are necessary but not sufficient to trigger periodontitis (Socransky & Haffajee, 1992; Van Dyke, 2008). The tissue destruction in periodontitis is a consequence of an imbalance in the homeostatic relationship between tissue resorption and tissue genesis, such that tissue resorption is favoured under the influence of an unregulated inflammatory response to the pathogenic bacteria within the periodontal crevicular space and as alluded to above, other non-microbial factors (Deas, Mackey, & McDonnell, 2003; Van Dyke, 2008;

Sanz & van Winkelhoff, 2011). Susceptibility to disease, progression, severity, and response to treatment are determined mostly by host-based factors (Kinane, Peterson, & Stathopoulou, 2006). The clinical presentation of chronic periodontitis includes loss of alveolar bone, bleeding upon probing, tooth mobility, and ultimately, if the disease is left untreated, tooth loss (Pihlstrom, Michalowicz, & Johnson, 2005). In addition to effects on the periodontium caused by periodontitis, it is also noteworthy that as a consequence of the disease and its treatment, those with periodontal disease have an increased risk for root caries (Boehm & Scannapieco, 2007). Therefore, periodontitis increases the risk for loss of teeth due to the disease itself, but in the longer term tooth loss is also due to an increased risk for root caries, a form of tooth decay that proceeds rapidly and can have rather devastating effects on the teeth. Premature loss of teeth can lead to several problems including but not limited to the following: loss of masticatory function, malnutrition that could worsen the general health, speech difficulties, and an overall decrease in quality of life (Boehm & Scannapieco, 2007;

Brennan, Spencer, & Roberts-Thomson, 2007).

The Oral and Systemic Health Connection The importance of oral health with respect to overall health and well-being has been recognized by an increasing body of literature illustrating the association between periodontal health and general health in conditions such as diabetes mellitus, cardiovascular disease, and pulmonary infections (Scannapieco, 1999; Rutkauskas, 2000; Kinane & Marshall, 2001; Teng et al., 2002; Scannapieco, 2005a; Azarpazhooh & Leake, 2006;

Raghavendran, Mylotte, & Scannapieco, 2007; Kuo, Polson, & Kang, 2008; Azarpazhooh & Tenenbaum, 2012a). The connection lies at the thin and permeable gingival sulcus, which serves as a barrier between the oral environment and underlying tissues. In fact, this is the only area in the human body where the integumentary system is actually penetrated by another structure. The junctional epithelium is highly porous, as epithelial cells are connected by desmosomes and few gap junctions, resulting in large fluid-filled intracellular spaces (Bosshardt & Lang, 2005). In the presence of inflammation, this barrier may be penetrated easily by microorganisms that enter the underlying vasculature, thereby presenting a biological challenge to other parts of the body (Scannapieco, 2005a). Efforts to establish a causal link between oral and systemic diseases appear to be fading in favor of research focusing on the likely similar inflammatory mechanisms which underlie both oral and nonoral disease pathways (Kantarci & Van Dyke, 2005; Teles & Wang, 2011; Vaishnava, Narayan, & Fuster, 2011), where the term „Inflammatory Syndrome‟ may better and more appropriately describe the connection and commonalities between oral and general health and disease mechanisms (Azarpazhooh & Tenenbaum, 2012b).



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