Pauline Ford

Immunological differences and similarities between chronic periodontitis and aggressive periodontitis.

Chronic periodontitis is an inflammatory response in the periodontal tissues, which is elicited by the microorganisms present in dental plaque. The clinical manifestation of the disease is dependent upon the nature of this response, which, in turn, is determined by the patient s innate susceptibility. Chronic periodontitis in adults typically follows a cyclical course, with some forms remaining stable over many years and other forms progressing with subsequent tooth loss despite extensive treatment (44, 49). The initial immune response in chronic periodontitis occurs following colonization of the gingival sulcus by periodontopathic bacteria. The presence of the bacteria induces the production of cytokines and chemokines by the gingival epithelium. This results in the expression of adhesion molecules, increased permeability of gingival capillaries and chemotaxis of polymorphonuclear neutrophils through the junctional epithelium and into the gingival sulcus. The specific cytokines and chemokines produced by this initial response lead to a perivascular T-cell ⁄ macrophage dominated inflammatory infiltrate in the connective tissues. If this cell-mediated immune response does not control the bacterial challenge, progression to a B-cell ⁄ plasma-cell lesion occurs. The antibodies subsequently produced may be protective and control the infection, or may be nonprotective with resultant connective tissue destruction and bone loss (reviewed in 42,44). The effectiveness of this response varies among individuals and appears to be important in determining disease susceptibility. Currently, however, there is little evidence that aggressive periodontitis, either localized or generalized, follows the typical cyclical course of chronic periodontitis. Additionally, aggressive periodontitis appears to differ from chronic periodontitis in that clinically the gingival lesion is often absent, suggesting that the lesion of aggressive periodontitis may not follow the same sequence of initiation and progression as chronic periodontitis (from gingival T-cell lesion to progressive B-cell lesion). While further investigation of the nature of the immune response in both chronic periodontitis and aggressive periodontitis is clearly required, this review is not a comprehensive analysis of the immunopathology of these conditions but rather will cover only those elements where a direct comparison of similarities or differences is possible or where further work may highlight possible differences.

Characterization of heat shock protein-specific T cells in atherosclerosis.

ABSTRACT A role for infection and inflammation in atherogenesis is widely accepted. Arterial endothelium has been shown to express heat shock protein 60 (HSP60) and, since human (hHSP60) and bacterial (GroEL) HSP60s are highly conserved, the immune response to bacteria may result in cross-reactivity, leading to endothelial damage and thus contribute to the pathogenesis of atherosclerosis. In this study, GroEL-specific T-cell lines from peripheral blood and GroEL-, hHSP60-, and Porphyromonas gingivalis-specific T-cell lines from atherosclerotic plaques were established and characterized in terms of their cross-reactive proliferative responses, cytokine and chemokine profiles, and T-cell receptor (TCR) Vβ expression by flow cytometry. The cross-reactivity of several lines was demonstrated. The cytokine profiles of the artery T-cell lines specific for GroEL, hHSP60, and P. gingivalis demonstrated Th2 phenotype predominance in the CD4 subset and Tc0 phenotype predominance in the CD8 subset. A higher proportion of CD4 cells were positive for interferon-inducible protein 10 and RANTES, with low percentages of cells positive for monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α, whereas a high percentage of CD8 cells expressed all four chemokines. Finally, there was overexpression of the TCR Vβ5.2 family in all lines. These cytokine, chemokine, and Vβ profiles are similar to those demonstrated previously for P. gingivalis-specific lines established from periodontal disease patients. These results support the hypothesis that in some patients cross-reactivity of the immune response to bacterial HSPs, including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may explain the apparent association between atherosclerosis and periodontal infection.

Cardiovascular and oral disease interactions: what is the evidence?

This paper reviews the evidence for the interaction of oral disease (more specifically, periodontal infections) with cardiovascular disease. Cardiovascular disease is a major cause of death worldwide, with atherosclerosis as the underlying aetiology in the vast majority of cases. The importance of the role of infection and inflammation in atherosclerosis is now widely accepted, and there has been increasing awareness that immune responses are central to atherogenesis. Chronic inflammatory periodontal diseases are among the most common chronic infections, and a number of studies have shown an association between periodontal disease and an increased risk of stroke and coronary heart disease. Although it is recognised that large-scale intervention studies are required, pathogenic mechanism studies are nevertheless required so as to establish the biological rationale. In this context, a number of hypotheses have been put forward; these include common susceptibility, inflammation via increased circulating cytokines and inflammatory mediators, direct infection of the blood vessels, and the possibility of cross-reactivity or molecular mimicry between bacterial and self-antigens. In this latter hypothesis, the progression of atherosclerosis can be explained in terms of the immune response to bacterial heat shock proteins (HSPs). Because the immune system may not be able to differentiate between self-HSP and bacterial HSP, an immune response generated by the host directed at pathogenic HSP may result in an autoimmune response to similar sequences in the host. Furthermore, endothelial cells express HSPs in atherosclerosis, and cross-reactive T cells exist in the arteries and peripheral blood of patients with atherosclerosis. Each of these hypotheses is reviewed in light of current research. It is concluded that although atherosclerotic cardiovascular disease is almost certainly a multifactorial disease, there is now strong evidence that infection and inflammation are important risk factors. As the oral cavity is one potential source of infection, it is wise to try to ensure that any oral disease is minimised. This may be of significant benefit to cardiovascular health and enables members of the oral health team to contribute to their patients’ general health.

Malignant transformation of oral epithelial dysplasia: a real-world evaluation of histopathologic grading

OBJECTIVE This study describes the predictive value of oral epithelial dysplasia (OED) grading as an indicator for malignant transformation and progression. STUDY DESIGN The records of an Australian-based pathology laboratory were searched for oral mucosal biopsies with a dysplastic or malignant diagnosis. Examination for an association with progression and malignant transformation without reinterpretation was performed. Analysis was undertaken using hazard ratios and the Fisher exact test. RESULTS A total of 368 patients with a diagnosis of OED were included. Twenty-six patients (7.1%) underwent progression or malignant transformation; the annual malignant transformation rate was 1%. No other characteristics were associated with a heightened risk of progression or transformation. CONCLUSIONS The severity of OED was not associated with risk of malignant transformation, suggesting that the current OED grading system is not useful for predicting patient outcomes or for determining management strategies. Definitive treatment of all OED is recommended, until a more reliable progression/transformation system is developed.

Prevalence and severity of oral disease in adults with chronic kidney disease: a systematic review of observational studies

BACKGROUND Oral disease may be increased in people with chronic kidney disease (CKD) and, due to associations with inflammation and malnutrition, represents a potential modifiable risk factor for cardiovascular disease and mortality. We summarized the prevalence of oral disease in adults with CKD and explored any association between oral disease and mortality. METHODS We used systematic review of observational studies evaluating oral health in adults with CKD identified in MEDLINE (through September 2012) without language restriction. We summarized prevalence and associations with all-cause and cardiovascular mortality using random-effects meta-analysis. We explored for sources of heterogeneity between studies using meta-regression. RESULTS Eighty-eight studies in 125 populations comprising 11 340 adults were eligible. Edentulism affected one in five adults with CKD Stage 5D (dialysis) {20.6% [95% confidence interval (CI), 16.4-25.6]}. Periodontitis was more common in CKD Stage 5D [56.8% (CI, 39.3-72.8)] than less severe CKD [31.6% (CI, 19.0-47.6)], although data linking periodontitis with premature death were scant. One-quarter of patients with CKD Stage 5D reported never brushing their teeth [25.6% (CI, 10.2-51.1)] and a minority used dental floss [11.4% (CI, 6.2-19.8)]; oral pain was reported by one-sixth [18.7% (CI, 8.8-35.4)], while half of patients experienced a dry mouth [48.4% (CI, 37.5-59.5)]. Data for kidney transplant recipients and CKD Stages 1-5 were limited. CONCLUSIONS Oral disease is common in adults with CKD, potentially reflects low use of preventative dental services, and may be an important determinant of health in this clinical setting.

A Systematic Review of Peer-Support Programs for Smoking Cessation in Disadvantaged Groups

The burden of smoking is borne most by those who are socially disadvantaged and the social gradient in smoking contributes substantially to the health gap between the rich and poor. A number of factors contribute to higher tobacco use among socially disadvantaged populations including social (e.g., low social support for quitting), psychological (e.g., low self-efficacy) and physical factors (e.g., greater nicotine dependence). Current evidence for the effectiveness of peer or partner support interventions in enhancing the success of quit attempts in the general population is equivocal, largely due to study design and lack of a theoretical framework in this research. We conducted a systematic review of peer support interventions for smoking cessation in disadvantaged groups. The eight studies which met the inclusion criteria showed that interventions that improve social support for smoking cessation may be of greater importance to disadvantaged groups who experience fewer opportunities to access such support informally. Peer-support programs are emerging as highly effective and empowering ways for people to manage health issues in a socially supportive context. We discuss the potential for peer-support programs to address the high prevalence of smoking in vulnerable populations and also to build capacity in their communities.

Developing information literacy with first year oral health students

CONTEXT In this time of rapid expansion of the scientific knowledge base, subject matter runs the risk of becoming outdated within a relatively short time. Instead of adding more content to already crowded curricula, the focus should be on equipping students to adapt to their changing world. The ability to access, evaluate and apply new knowledge for the benefit of patients has been acknowledged as an important goal for dental education. Information literacy is key to achieving this. METHODS An information literacy programme for first year oral health students was instituted. This was integrated within a biosciences course and linked with its assessment. Small group instruction reinforced by the use of a tailored online Assignment Guide was used in the context of a specific task. Effectiveness was measured in terms of assessment outcome, processes used and student experience. RESULTS Twenty-seven students participated in the intervention which was effective in enhancing foundation literacy skills and confidence of students in accessing and evaluating information sources in the context of a clinical problem. Improvement in higher level literacy skills required to articulate this information in the synthesis of a scientific review was not demonstrated. CONCLUSIONS Integration of this information literacy programme within the learning activities and assessment of a basic sciences course resulted in significantly enhanced information literacy skills. As this is highly relevant for higher education students in general, the wider promotion of information literacy should be encouraged.

A retrospective analysis of clinical features of oral malignant and potentially malignant disorders with and without oral epithelial dysplasia

OBJECTIVE Clinical identification of underlying histopathology of oral mucosal lesions (OMLs) remains difficult. The study aims to identify clinical indicators of underlying histopathology of oral malignant and potentially malignant disorders. STUDY DESIGN All clinical patient records of an oral medicine and pathology clinic over a 12-year period were manually searched. Cases of OMLs with a histopathologic diagnosis of dysplasia (n = 124) and malignancy (n = 27) and a sample of nondysplastic OMLs (n = 109) were analyzed using both univariate and multivariate analysis and odds ratios for an association with clinical characteristics. RESULTS A nonhomogeneous clinical appearance was strongly associated with underlying dysplasia in both univariate and multivariate analysis (P < .001; odds ratio, 4.4). For lesions with homogeneous appearance, dysplasia was associated with lesion location (P = .005; odds ratio, 2.6) and smoking history (P = .04). CONCLUSIONS These findings suggest that a nonhomogeneous mucosal lesion is a significant independent indicator for underlying oral epithelial dysplasia, with location, size, and color as additional contributing factors.

Support needs and quality of life in oral cancer: a systematic review.

PURPOSE This review aims to systematically review the literature describing quality of life (QoL) outcomes and support needs in patients with oral cancer along the cancer trajectory. This is needed to form an evidence base for the design of interventions that enhance outcomes for this group. METHODS Six electronic databases were searched. The results were screened for eligibility, and articles were included if they described patient-reported QoL outcomes that were translatable to support needs in patients with oral cancer. Data were extracted and synthesized according to the support needs identified and their relative impact on QoL. Methodological quality was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool. RESULTS Thirty-one articles met the inclusion criteria. Support needs related to coping with the burden of radiotherapy in both psychosocial and physical aspects, swallowing dysfunction, dry mouth and oral functional deficits. Issues of depression, anxiety and malnutrition were identified as having a significant impact on QoL. CONCLUSIONS Oral cancer support needs are highly subjective and varied in severity across the cancer continuum. Support needs that may warrant further investigation include management of changes to oral health and functioning, swallowing and nutritional compromise and psychological effects of cancer and treatment.

Cardiovascular disease and the role of oral bacteria.

Abstract In terms of the pathogenesis of cardiovascular disease (CVD) the focus has traditionally been on dyslipidemia. Over the decades our understanding of the pathogenesis of CVD has increased, and infections, including those caused by oral bacteria, are more likely involved in CVD progression than previously thought. While many studies have now shown an association between periodontal disease and CVD, the mechanisms underpinning this relationship remain unclear. This review gives a brief overview of the host-bacterial interactions in periodontal disease and virulence factors of oral bacteria before discussing the proposed mechanisms by which oral bacterial may facilitate the progression of CVD.