COPD includes chronic bronchitis and emphysema, Murray et al has predicted that COPD would become the third most common cause of death and the fourth most important disease leading to disability by 2020 
. PD is considered a novel risk factor, in addition to smoking, chronic exposure to hazardous air pollutants, and genetic conditions 
. Our meta-analysis of one nested case-control study, eight case-control studies, and five cross-sectional studies provides evidence that PD is associated with an increased risk of COPD and can increase a significantly the risk by 2.08 times. When the subjects were stratified by ethnicity, this association did not differ: the ORs were 1.69 for North Americans (95%CI
1.43–2.00), 1.93 for Asians (95%CI
1.15–3.26), and 3.89 for Europeans (95%CI
2.05–7.38). When the analysis was restricted to studies with control for conventional rsik factors, including age, gender, and especially smoking, PD was identified as a probable independent risk factor for COPD (OR
<0.001). When the groups were stratified the group by study design, the results also suggested that PD is a significant risk factor for COPD in both case-control and cross-sectional studies, with the association gaining more powerful from the cross-sectional studies (OR
<0.001) to the case-control studies (OR
<0.001) to the nested case-control study (OR
<0.001). This finding can be attributed to the fact that the cross-sectional study design suffers from more confounding biases compared with the case–control study design and the case–control study design suffers from more confounding biases compared with the nested case–control study design. The prospective cohort study design is the best among observational studies, and it can control confounding biases very well. We therefore suggest that this study design be used in future research.
Oral cavity has been recognized as a potential reservoir for respiratory pathogens 
, and dental plaque may play an important role in its formation, which may also contribute to PD 
. Colonization of dental plaque by respiratory pathogens followed by aspiration has been proposed as a possible mechanism, but data on whether the same pathogens are isolated in PD and COPD exacerbations are limited. Epidemiological studies have found evidence favoring this association; however, debate on this issue has ensued over recent decades. Our meta-analysis detected a significant association between PD and COPD with and without adjustments made on the conventional risk factors. This suggests that an effective oral hygiene regimen would effectively prevent the progression of COPD, and that an effective PD intervention treatment should be able to control COPD. Correct and effective brushing of teeth, use of dental floss, and regular periodontal scaling would be the simplest and most cost-effective actions. To substantiate these findings, we recommend that sufficient relevant randomized controlled trials be carried out to test whether periodontal interventions can affect the progression of COPD. Moreover, we suggest that fundamental studies investigating the true mechanism between PD and COPD be performed, particularly to identify which role or roles would take much of the responsibility and whether the pathogens isolated in PD exacerbations are the same as those isolated in COPD exacerbations — which can give clearer guidelines for clinical practice and make the link between the two diseases more convincing. In addition, a spacer device and cold water for rinsing should be used in COPD patients undergoing treatment that requires steroid inhalation to reduce the accumulation of steroids in the mouth cavity; similarly, when a metered-dose inhaler is used for steroid inhalation, a spacer device should be applied to reduce the possibility for respiratory pathogens in dental plaque to move into the lung.
The main strength of this study was pooling data from individual studies with small sample sizes and a low statistical power via meta-analysis approach. We also collected studies as relevant as possible and used subgroup and sensitivity analyses to test the robustness of the results. This meta-analysis overcame the shortcomings of two pervious systematic reviews (our meta-analysis also included the five studies 
that used in those systematic reviews) 
However, this study also had some limitations. First, although meta-analysis is a useful tool in epidemiology, problems associated with methodology may limit its benefits. Case-control study and cross-sectional studies are not the best designs among observational studies; thus, evidence from these studies is likely to be less accurate and possibly more influenced by recall bias compared with that from cohort studies. In addition, meta-analysis is a secondary analysis approach and has some inevitable biases. Second, some pooled ORs were obtained from heterogeneous studies, although we performed sensitivity analyses. Third, the funnel plot of publication bias showed that it was asymmetrical, and publication bias thus had to be considered. This suggests that we may have missed important unpublished studies with results inconsistent with our findings, although we did our best to collect all relevant studies. The filled funnel plot showed that two additional unpublished studiesare needed to negate the results of our meta-analysis. Fourth, none of the 14 studies were selected in our meta-analysis provided the degrees of PD and risk of COPD such that we could not conduct a dose-response analysis to assess their relationship more precisely. Fifth, the prevalence/incidence of COPD in developing countries (where access to dental care is limited) is presumably much higher than that in developed countries (where access to dental care is better), but we could not obtain current and relevant data to verify this. As PD and COPD share many risk factors, further research should analyze whether the association between them is causal using validated and optimal measurement tools (eg., Community Periodontal Index of Treatment Needs 
for PD and FEV1/FVC for COPD 
), calculate the interval between the onset of each disease, and consider adequate control for the confounding factors.