The findings are reported in two main sections. First, the nature of association between oral and pulmonary disease, including whether or not the latter is more likely in patients with oral disease. Second, the evidence from studies that have tested the impact of oral hygiene measures on pulmonary disease incidence and outcomes.
A] Association between oral and pulmonary disease
Overall the literature suggests associations of varying strength between oral health (periodontitis, caries, and plaque) and pulmonary disease (COPD and pneumonia). This was demonstrated by the increased presence of oral disease, or oral pathogens, in those participants who developed pulmonary disease when compared with those who did not. No evidence was discovered regarding any association between oral health and the presence of other conditions, notably lung cancer or tuberculosis. In the next sections, evidence of the associations between individual oral diseases and COPD and pneumonia are presented.
I] Periodontitis and COPD
In the case of periodontitis and COPD, three reviews of moderate methodological quality highlight an association between COPD and periodontal disease. The first, by Azarpazhooh and Leake,35 provided weak evidence of an association between COPD and periodontal disease, suggesting study participants with significantly higher alveolar bone loss (ABL) and loss of clinical attachment had a higher risk of COPD than their counterparts. The second review by Sjogren et al.33 also highlighted a weak association between ABL and dental plaque with COPD. And a third by Zeng et al.34 reviewed fourteen observational studies assessing the relationship between COPD and periodontal disease and included pooled data stratified to control for smoking and other risk factors associated with the two diseases; the stratified results showed an attenuated, but significant, association between COPD and periodontal disease (P <0.001).
II] Periodontitis and pneumonia
Azarpazhooh and Leake (2006)35 reviewed five studies that explored the relationship between pneumonia and oral health, suggesting that periodontal pathogens in saliva are a potentially important risk factor for pneumonia. No evidence was found linking periodontal disease itself with pneumonia.
III] Caries and pneumonia
The presence of caries was linked to the development of pneumonia in one moderate quality review,35 which reported evidence from a nine-year cohort study indicating that decayed teeth (that is, dental caries) ([OR] ∼1.2 per decayed tooth) and cariogenic bacteria in saliva and plaque ([OR] 4 to 9.6) were associated with a higher risk of pneumonia.35
IV] Plaque and pneumonia
Plaque, and its association with pulmonary disease, was examined by one moderate quality review. The evidence to support this was mixed with two prospective cohort studies suggesting that higher plaque scores were associated with a previous history of respiratory tract infection, whilst a third found no such significant association between pneumonia and plaque scores.35
In summary, there is moderate evidence to suggest that patients with caries and plaque have a higher likelihood of developing pneumonia, and weak evidence suggesting an increased likelihood of people with more alveolar bone loss developing COPD than comparable counterparts.
B] Effect of oral hygiene interventions on incidence and outcomes of pulmonary disease
In this section the impact of oral hygiene interventions is reported in two sub-sections: first in relation to community or hospital patients; and, second, in relation to ventilated patients.
I] Effect of oral hygiene interventions on incidence and outcomes of pulmonary disease in community or hospital patients
Several reviews described oral hygiene interventions and their impact on incidence, or outcomes, of pneumonia in non-ventilated patients in community or hospital environments, while no evidence was found regarding any other pulmonary disease (including COPD). Therefore, this section will solely deal with oral hygiene inventions and their effects on pneumonia. These interventions include the use of chlorhexidine with concentrations between 0.12–2.0%, povidone iodine, the cleaning of prostheses, and mechanical interventions such as toothbrushing or professional care involving scaling and polishing.
a) Incidence of pneumonia in community and hospital patients
Seven systematic reviews investigated the relationship between oral hygiene interventions and incidence of pneumonia in these patients, and all suggest there is good evidence that oral hygiene interventions (chlorhexidine, toothbrushing, professional oral care, povidone iodine) reduce the risk of pneumonia.28,29,30,31,32,33,35 The review quality ranged from high,16,26,28 which included a meta-analysis, to moderate.31,32,33,35 Two reviews suggest that there is a reduced risk of pneumonia with combined effect of mechanical and professional care,28,33 and a third by Van der Maarel-Wierink et al.32 suggests that manual toothbrushing, with or without povidone iodine, reduced the risk of pneumonia in frail older people by 67%. Of note, while mechanical plaque removal was shown to reduce pneumonia incidence in non-ventilated patients, this result was not repeated for ventilated patients.
In summary, there is good evidence that oral hygiene interventions reduce the risk of pneumonia in community and hospital patients.
b) Outcomes of pneumonia
Three high to moderate quality reviews found that mortality was reduced by mechanical plaque removal in community and hospital patients.19,28,32 One high quality review by Silvestri et al. suggested no significant impact of chlorhexidine on pneumonia-associated mortality, although this paper included both ventilated and non-ventilated hospital patients.29 Kaneoka et al.28 in a high quality review, suggest that there is moderate evidence from two randomised, controlled trials, that mechanical oral care can lead to a risk reduction in fatal pneumonia but highlight a need for caution due to a risk of possible bias in the included studies.19 Similarly, two studies included in the systematic review by Van der Maarel-Wierink et al.32 found that toothbrushing without povidone iodine reduced pneumonia mortality (RR = 2.40 and 95% CI = 1.54–3.74 and OR = 3.57; 95% CI = 1.13–13.70).
Two high quality reviews suggest that the number of febrile days may be reduced by implementing oral health interventions.17,29 One review found that toothbrushing with 1% iodine, or scaling combined with electric toothbrushing led to a reduction in febrile days.30 These reviews do not include meta-analysis and should therefore be considered with caution.
Use of topical antiseptics and professional oral health care both appear to reduce microbial colonisation of the oral cavity. In a high quality review, Silvestri et al.,29 report that chlorhexidine controls both gram-positive and gram-negative bacteria-related pneumonia as well as most (but not all) specific pneumonia-causing bacteria such as Streptococcus pneumoniae or Haemophilus influenza. However, when micro-organisms are classified into 'normal' and 'abnormal', chlorhexidine significantly reduces pneumonia due to 'normal' flora only.29 One study in the review by Van der Maarel-Wierink et al.32 suggests a reduction in levels of potential respiratory pathogens (Streptococci, Staphylococci, Candida, Pseudomonas, and Black-pigmented Bacteroides species) after weekly professional oral healthcare. Professional oral care being defined as mechanical cleaning by a dentist/hygienist which varied in frequency from one to three times weekly.
A moderate quality review by Van der Maarel-Wierink et al., which examined known risk factors for aspiration pneumonia reported an improvement in four out of five risk factors (swallowing latency time, activities of daily living scale, swallowing reflex, cough reflex sensitivity; but not salivary substance P) associated with regular oral hygiene.32
In summary, good to moderate evidence suggests that oral hygiene interventions reduce many of the outcomes of pneumonia including febrile days, microbial colonisation, and mortality with the latter primarily being reduced by mechanical plaque removal.
II] The effect of oral hygiene interventions on incidence and outcomes of pulmonary disease in ventilated patients
There is a significant body of evidence relating to the effect of oral hygiene interventions on VAP, although no evidence regarding any other pulmonary disease. Again, this section focused on pneumonia and examines their impact on incidence and outcome, as well as cost-effectiveness and the role of different agents.
a) Incidence of VAP
In mechanically ventilated patients there is strong evidence from 13 systematic reviews that use of chlorhexidine (gel or mouthwash), when used in concentrations varying from 0.12–2.0%, reduces the risk of incidence of VAP.14,16,17,18,19,20,21,24,26,27,29,30,31 Only one moderate-quality study,25 the oldest included, did not find a significant reduction. The pooled relative risk of acquiring VAP reduced by approximately 40% when chlorhexidine-based oral decontamination was provided to ventilated patients in comparison to control groups (specifics of control groups varied among studies and included toothbrushing, 'standard oral care', placebo, other oral decontaminants, sterile water. Five reviews (two high, two moderate and one low quality) suggest the number needed to treat (NNT) as between 8 and 21 (with the high quality reviews finding a NNT of 14 and 15); meaning that between 8 and 21 ventilated patients in intensive care need to receive chlorhexidine oral decontamination for one case of VAP to be prevented.20,22,26,27,33 Mechanical toothbrushing in addition to the use of chlorhexidine was not found to reduce the incidence of VAP by three high quality, and one moderate quality reviews.14,15,20,23
In summary, there is strong evidence that regular chlorhexidine use in ventilated patients reduces the risk of VAP; with no evidence to show that mechanical plaque removal in addition to chlorhexidine provides further benefit.
b) Outcomes of VAP
No significant effect on mortality, duration of mechanical ventilation or duration of hospital stay was demonstrated,14,17,18,19,20,22,24,25,26 and no evidence was found of a difference between chlorhexidine and placebo for the outcomes of VAP and mortality in children.20 Other notable outcomes were that the use of chlorhexidine had a greater treatment effect in cardio-surgical patients,24,29,36 and authors postulated that this was related to the planned nature of the intubation and the physical status of the patient at the time.
In relation to the impact of oral interventions on the use of systemic antibiotic therapy, Shi et al.,20 a high quality review based on two randomised clinical trials, reported no significant difference in duration of antibiotic therapy, for the management of VAP, between intervention and control groups. One high quality systematic review, including four randomised-controlled trials, found no significant difference in antibiotic-free days between patients who received oral care and the control group.15
Four reviews,20,23,24,30 of high to medium quality, include evidence regarding oral health indices, in particular plaque scores. El-Rabbany et al.,30 in a high quality review suggest that toothbrushing does improve oral health and has a positive effect on plaque scores when used on ventilated patients. It is suggested that this will reduce VAP, although as mentioned above, four reviews found toothbrushing had no effect. They do clarify that the studies reviewed were of moderate to high risk of bias. Two reviews,23,24 report lower plaque levels in chlorhexidine groups versus controls in five trials, while one trial showed no such difference.
Shi et al.20 reported the effect on plaque scores for toothbrushing versus no brushing and the use of chlorhexidine plus brushing versus a control group with chlorhexidine alone. The studies were of moderate to high risk of bias and presented ambivalent conclusions, when compared. One study indicated that plaque scores were improved, whereas the other three showed no difference.
In relation to microbial colonisation, Shi et al. found insufficient reliable and consistent evidence to confirm whether microbial colonisation of dental plaque varied between intervention and control groups for VAP.20 On adverse effects of the interventions, two high and one moderate quality review18,20,24 considered adverse effects in the evidence from the studies they included. One study reported that three patients receiving chlorhexidine complained of a transient, unpleasant taste and this compared to five patients in the control arm of the study.20 In a further study, 9.8% of patients receiving chlorhexidine complained of mucosal irritation compared with 1% of the control group.20 Snyder et al.18 concurred with the comments from this study but added that further instruction to staff to be more gentle reduced the reports of irritation. Chlebicki et al.24 reported no adverse effects.
Adverse effects/side effects reported were transient in nature and were reported in relation to both the chlorhexidine intervention and the control groups. The adverse effects of chlorhexidine were not unexpected and are those described within the drug proprietary literature. There was no reported evidence on the effect of oral hygiene interventions on the number of febrile days for ventilated patients.
In summary, there is moderate to low quality evidence that chlorhexidine does not have an effect on the following outcomes of VAP: mortality; duration of hospital stay; duration of ventilation; antibiotic use; plaque scores; microbial colonisation; or VAP in children. No unexpected side-effects of chlorhexidine were found.
c) Cost-effectiveness
Three systematic reviews reported on the cost-effectiveness of chlorhexidine as an oral care intervention.16,18,24 Where chlorhexidine reduced the incidence of VAP by 43%, the comparative cost of a ye ar's supply of chlorhexidine (Peridex) was less than 10% of the cost associated with a single case of VAP.16 The cost of chlorhexidine therapy for fourteen patients was suggested to be less than 10% of the cost of antibiotic therapy alone for one case of VAP.16
Snyders et al.18 also included two trials that considered the cost-effectiveness of chlorhexidine. Both suggested that chlorhexidine was cost-effective, and one suggested that the cost-effectiveness may be as much as ten times less per patient than the cost of antibiotics to treat VAP.18 Chlebicki et al.24 quotes studies examining costs of chlorhexidine, but notes no formal cost-effective analysis.
In summary, good evidence suggests that chlorhexidine is cost-effective when used to reduce pneumonia incidence.
d) Other antimicrobial agents
The effectiveness of topical application of povidone iodine for oral disinfection was considered in five systematic reviews of which four were high quality.16,19,27,29 There is weak evidence that povidone iodine reduces the incidence of pneumonia, but this mode of oral disinfection was less effective than the use of chlorhexidine.17,20,28,30,32
In summary, moderate evidence suggests both mechanical and chemical interventions have an impact on the incidence and outcomes of pneumonia in community and hospital patients. In regards to VAP, there is strong evidence that chemical interventions in general reduce incidence but do not affect other patient outcomes.
