Mouth the mirror of lungs: where does the connection lie?

Abstract

Periodontitis is the chronic destructive disease of the periodontium (Gums) caused by host bacterial interactions. The effect of such host bacterial interactions in oral cavity also evokes a systemic response. Numerous studies have found common mechanisms of destruction for periodontal diseases and other chronic diseases like diabetes mellitus, atherosclerosis, respiratory diseases, and adverse pregnancy outcomes. Oral colonization by respiratory pathogens appears to be a risk factor for development of respiratory diseases and oral interventions aimed at reducing oral bacterial count have resulted in reduced incidence of these reparatory illness. This reflects the importance of oral hygiene among patients with respiratory illness. This review highlights the association between periodontal diseases and respiratory diseases.

Keywords

periodontitis / respiratory diseases / acute pneumonia / COPD

Introduction

The oral systemic link termed as “periodontal medicine” has gained particular attention over the past few decades as it is of great public health significance. Researchers have particularly focused on the relationship between periodontitis and systemic diseases and have found a definitive statistical relationship on how periodontitis aggravates systemic disease [ 1]. American Academy of Periodontology has rightly stated that bacteria from the periodontal region enter systemic circulation and begin new infections in other target organs. They have also stated that the periodontal infections can pose a serious threat to individuals whose health is compromised by other conditions like diabetes mellitus, respiratory disease, or osteoporosis [ 2].

The concept of focal infection with relation to oral diseases dates back to the eighteenth century. Periodontal disease is by far the most common oral infection caused by bacteria in dental plaque. These bacteria start a series of inflammatory events that destroy the periodontium and severe periodontal disease causes bacteria to enter the blood stream.

There are three ways in which periodontal disease poses a threat [ 3]: (1) subgingival biofilm—accumulates bacteria and provides an easy access to general circulation; (2) shared risk factors—age, ethnicity, smoking, stress, etc. are common to periodontal disease as well as other systemic diseases; (3) periodontium—cytokine reservoir—periodontal pathogens secrete wide range of cytokines that exert a generalized systemic effect.

Potential respiratory pathogens (PRPs) — dental plaque as reservoir

The oral cavity is proximal and contiguous with the trachea and therefore a logical portal for respiratory pathogen colonization. The pathogenesis of pneumonia depends on the aspiration of microorganisms from oropharyngeal or oronasal region into the lungs. The upper respiratory tracts were frequently contaminated by the microorganisms from the oropharyngeal region whereas lower respiratory tract is relatively free of them. Once infected by these microorganisms, under normal circumstances, the host defense mechanism will eliminate the infection. But in an immune compromised state, the host response turns destructive and results in lung infection [ 4].

Community acquired pneumonia is mainly caused by inhalation of infectious aerosols. Main infective organisms are Streptococcus pneumonia and Hemophilus influenenzae. So far no association has been found between periodontal diseases and community acquired pneumonia [ 5]. In hospital acquired pneumonia, the main etiological organism is Staphylococcus aureus. It spreads through infected particulate nuclei in air.

In ventilator associated pneumonia, the intubation translocates the oropharyngeal organisms into trachea. The biofilm can also become dislodged and embolize to set up foci of infection [ 6]. Studies have found more significant increase in dental plaque scores in intensive care patients than other normal subjects. Furthermore, these subjects had more PRPs in dental plaque and buccal mucosa as compared to other subjects [ 7].

Studies have reported that respiratory pathogens preferentially colonize the teeth or dentures, rather than soft tissue [ 8– 10]. Fourrier et al. stated that there is a 9.6 fold increase in risk of developing pneumonia when the dental plaque contains PRP between 0-5 days following hospitalization [ 11]. The importance of aspiration of bacteria found in dental plaques in the causation of healthcare-associated pneumonia has been invoked by these studies in which cultures of dental plaques have yielded pathogenic microorganisms that are prevalent etiologic agents of pneumonia [ 7– 11].

Didilescu et al. demonstrated increase in prevalence of respiratory pathogens such as S. aureus, P. aeruginosa, Acinetobacter baumannii, and Enterobacter cloacae in the dental plaque of hospitalized patients [ 12].

In a Japanese study dentate patients with poor oral hygiene showed significantly higher salivary bacterial counts than those with good oral hygiene [ 13]. Poor oral hygiene increases the complexity and mass of the dental plaque which fosters further interactions between indigenous plaque bacteria and respiratory pathogens [ 14]. These interactions result in colonization of the dental plaque by respiratory pathogens which are eventually shed into the saliva which when aspirated can contaminate the respiratory tree. The evidence suggests that dental plaque serves as an important reservoir of respiratory pathogens.

Moreover a variety of oral anaerobes and facultative species have been cultured from infected lung fluids, including Porphyromonas gingivalis, Bacteroides grucilus, Eikenella corrodens, Fusobacterium nucleutum, Fusobacterium necrophorum, Peptostreptococcus, Clostridium, and Actinomyces [ 15, 16].

Link between periodontal infection and lung diseases

Now that it has been established that the dental plaque serves as reservoir for PRPs, the question arises how bacteria from dental plaque is translocated to respiratory tree. Bacteria from the dental plaque are likely to be shed in the saliva. When this is aspirated, the bacteria are translocated to the lower respiratory trees and cause infection [ 17]. Moreover in subjects with high plaque scores, mechanical intubation is one of the main means of translocation of oral bacteria into the lungs [ 18]. It has also been suggested that translocation of oral pathogens via bacteremia is also important means of spread [ 19].

Potential mechanisms of action of oral bacteria in the pathogenesis of respiratory infection

Several mechanisms have been put forth to explain the connection between periodontitis and respiratory infections: (1) oral pathogens aspirated into lungs to cause infection; (2) periodontal disease-associated enzymes in saliva may modify mucosal surfaces to promote adhesion and colonization by respiratory pathogens; (3) periodontal disease-associated enzymes may destroy salivary pellicles on pathogenic bacteria; (4) cytokines originating from periodontal tissue may alter respiratory epithelium to promote infection by respiratory pathogens.

Periodontal disease-associated enzymes in saliva

Saliva contains many hydrolytic enzymes. These enzymes act on the mucosal epithelium and expose the “buried adhesion receptors.” This facilitates the adhesion and colonization of Gram negative respiratory pathogens [ 20].

Destruction of protective salivary pellicles by oral bacteria

The hydrolytic enzymes in the saliva also destroys the protective host components (e.g., mucins), thereby decreasing the nonspecific host defense against respiratory pathogens [ 20].

Cytokine mediated alteration of the respiratory epithelium

In response to the pathogens, the epithelial cells and cells of connective tissue produce a wide array of cytokines. These cytokines alter the adhesion molecules on the epithelium and initiate the bacterial adhesion onto the epithelial surfaces [ 20].

The overall mechanism is illustrated in Fig. 1

Periodontitis and COPD

Chronic obstructive pulmonary disease (COPD) is one of the major chronic debilitating diseases frequently seen in hospital settings. The disease appears usually after the age of 50 years and often predicts a shortened life span [ 21]. COPD primarily includes two entities—chronic bronchitis and emphysema. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines define COPD as a disease state characterized by airflow limitation that is not fully reversible, is usually progressive, and is associated with an abnormal inflammatory response of the lungs to inhaled noxious particles or gases [ 22]. Though numerous environmental factors are attributed to development of COPD, smoking is identified as the primary risk factor [ 23].

COPD and periodontitis share common pathogenic mechanisms

Smoking

Numerous studies suggest that smoking may act as a major effect modifier in the relationship between periodontitis and COPD [ 24]. Smoking is a well known risk factor for COPD and 80% of cases had been current or former smokers [ 25]. Smoking is also an important risk factor for development of periodontitis [ 26, 27].

Role of neutrophils

The key cell in the initiation of inflammation is the neutrophils and they are found in increased numbers in both COPD and periodontitis. Hyper responsive neutrophils and abnormal neutrophils functions in periodontitis influence reactive oxygen species mediated oxidative damage. These hyper responsive leukocytes are generally created in response to products from periodontal pathogens. These polymorphoneutrophils in lungs release various biologically active mediators resulting in mucosal damage and connective tissue destruction.

Clinical evidence

Hayes et al. in a longitudinal study conclude that alveolar bone loss was associated with the risk of COPD [ 28]. Scannapieco and Genco reported that poor oral hygiene and periodontal status are independent risk factors for COPD [ 29]. Scannapieco and Ho also proved that extent of periodontal attachment loss was positively associated with the risk for COPD [ 30, 31]. Prasana et al. in a study comprising of 100 patients demonstrated that all the periodontal parameters and periodontal index for risk of infectiousness was greater among the COPD group than the non COPD group [ 32].

However the evidence is still insufficient to declare an association between periodontitis and COPD. Scannapieco et al. in a systematic review that included 1688 studies stated that the results associating periodontitis and COPD are preliminary and large scale longitudinal and epidemiological studies are needed to come to any consensus [ 33].

Oral care and prevention of respiratory diseases

Effectiveness of oral decontamination to prevent pneumonia is studied extensively. Most of these trials, showed reductions in oral colonization by respiratory pathogens and/or incidence of pneumonia [ 34]. Studies have shown that the decontamination of digestive tract alone does not decrease the incidence of pneumonia, but the decontamination of oropharynx alone greatly decreased its incidence [ 35, 36].

Yoneyama et al. have demonstrated that in patients having constant oral health care, pneumonia, febrile days and death from pneumonia significantly decreases. He concluded that oral health care was beneficial in dentate patients [ 37].

Yoshida et al. found that pneumonia decreased significantly in patients with oral health care and suggested that oral health care may be useful in preventing pneumonia in institutionalised elderly irrespective of dentate or edentate status [ 38].

Ishikawa et al. showed that professional oral health care in dependent elderly patients reduced oropharyngeal bacteria like Streptococci, Staphylococci, Candida, Pseudomonas, and black pigmented rods decreased in a week. These findings indicate that weekly professional mechanical cleaning than daily chemical disinfection is an important strategy to prevent aspiration pneumonia [ 39]. Bassim et al. stated that oral health nursing intervention is an effective risk modifier of mortality from nursing home associated pneumonia [ 40].

On whole oral hygiene interventions reduce the rate of oral colonization by respiratory pathogens, thereby reducing the risk for pneumonia. Centre for Disease Control has included oral health care as an important measure to prevent ventilator associated pneumonia and recommends chlorhexidine usage every 4–6 h [ 41]. In institute for clinical systems improvement protocol for pneumonia prevention in ventilated patients, it is stated that assessing the oral cavity and oral care every 6–8 h and as needed, using a 0.12% or 2% chlorhexidine solution is a necessary measure to prevent ventilator associated pneumonia [ 42]. The hospital implemented oral care program to prevent aspiration pneumonia in ventilated patients includes the following: (1) tooth brushing — 2 – 4 h; (2) swabbing with alcohol free mouth rinse; (3) frequent suctioning of oral and pharyngeal secretions; (4) application of mouth moisturizers.

Conclusions

Oral colonization by respiratory pathogens appears to be a risk factor for development of respiratory diseases and oral interventions aimed at reducing oral bacterial count have resulted in reduced incidence of these reparatory illness. But further multicenter, randomized intervention trials are required to substantiate the present evidence.

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