Is periodontitis a comorbidity of COPD or can associations be explained by shared risk factors/behaviors?

Abstract

COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes. Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies. As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes. The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites. Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions. However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies. Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis. This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms. It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors. Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid illness and new therapeutic strategies for both the diseases. However, further research is needed to clarify factors that may be directly causal as opposed to confounding relationships.

Keywords: dental health; emphysema; inflammation; neutrophil; smoking.

Figure 1

Probing pocket depth (PPD – distance in millimeter from gingival margin to base of pocket) and clinical attachment loss (CAL – distance in millimeter from cement–enamel junction to base of pocket). Note: Copyright © 2002. Adapted with permission from Quintessence Publishing Co Ltd. Chapple ILC, Gilbert AD, Wilson NHF. Understanding Periodontal Diseases: Assessment and Diagnostic Procedures in Practice: 1 (Quintessentials: Endontics). Quintessence Publishing Co Ltd.

Figure 2

Shared inflammatory mechanisms that might facilitate disease progression in both COPD and periodontitis. Notes: (1) Periodontal bacteria are found in oral secretions and could result in systemic inflammation by two mechanisms. (2a) Inflammation of the periodontium causes production of local cytokines and other biologically active molecules that enter the systemic circulation by diffusion. These activate both the endothelium and circulating immune cells, which contribute to the inflammatory burden by the release of activating and destructive mediators. This process also occurs in the lungs, causing pulmonary inflammation. (3) Protective secretions and mucins are destroyed by neutrophils and hydrolytic salivary enzymes produced by bacteria. (4) Unresolved periodontal inflammation results in damage to periodontal tissue and alveolar bone. (5) Cytokines, bacteria, neutrophils, and other biologically activated mediators are aspirated into the respiratory tree and initiate bronchial inflammation perpetuated by upregulation of the expression of adhesion receptors on mucosal surfaces. (6) Pro-inflammatory mediators serve as an additional inflammatory stimulus and induce a more active response in the lungs. (7) Bronchial inflammation facilitates microbial colonization by oropharyngeal bacteria,,,, and local tissue destruction. (8) Infected and inflamed bronchial secretions increase the inflammatory load in the periodontium following expectoration. An alternative mechanism is represented in (2b). Periodontal pathogens enter gingival vasculature through micro-ulcerations in the epithelium allowing hematogenous dissemination of inflammatory mediators and bacteria. This bypasses stages 3–6 and has a resultant influence at stage 7.