Advanced Dental Cleaning is Associated with Reduced Risk of COPD Exacerbations - A Randomized Controlled Trial

Abstract

Purpose: Infections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes.

Patients and methods: One-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student's t-test and Mann-Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential confounders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models.

Results: In the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25-0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10-0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723).

Conclusion: Advanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.

Keywords: alpha diversity; beta diversity; health status; lung function; periodontal disease; plaque microbiome.

Figure 1

Flow chart. Adapted CONSORT flow chart of data collection, randomization, and follow-up.

Figure 2

Alpha diversity of microbiome. Alpha diversity as measured by observed richness and Shannon index, with comparison within each randomization group during follow-up and between randomization groups at baseline and at 12-month follow-up using Wilcoxon signed ranks tests.

Figure 3

Beta diversity of microbiome. PCoA plot of beta-diversity samples (small dots) and centroids (large dots). Difference in beta diversity based on per mutational multivariate analysis of variance.

Figure 4

Prediction of change in outcomes based on microbiota. Prediction of binarized outcomes from differences in abundance of microbiological features, using machine learning models with ROC-curves.