Chlorhexidine oral rinses for symptomatic COPD: a randomized, blind, placebo-controlled preliminary study

Background: Chlorhexidine oral rinses decrease ventilator-associated pneumonia but its effect on COPD is unknown.

Research Question: Will a preliminary study of the effect of twice-daily chlorhexidine oral rinses on oral and lung microbiota biomass and respiratory symptoms, compared to placebo, support the conduct of a larger clinical trial?

Study Design and Methods: Participants aged 40-85 with COPD and chronic respiratory symptoms were randomized 1:1 to twice-daily 0.12% chlorhexidine oral rinses vs. placebo.

Results: Forty-four participants were recruited between September 8, 2014 and May 30, 2019. Our primary outcome was a change in oral and sputum microbiota biomass during the study as assessed by 16S rRNA copy numbers. Neither the oral microbiota nor the sputum microbiota biomass decreased significantly in those using chlorhexidine compared with placebo (oral microbiota mean log10 difference [SE] = -0.103 [0.23], 95% CI: -0.59, 0.38, p=0.665; sputum microbiota 0.80 [0.46], 95% CI: -0.15, 1.75, p=0.096). Chlorhexidine decreased both oral and sputum microbiota alpha (Shannon) diversity (linear regression estimate [SE] oral: -0.349 [0.091], p=0.001; sputum -0.622 [0.169], p=0.001). Chlorhexidine use did not decrease systemic inflammatory markers compared to placebo (CRP [chlorhexidine 1.8 ± 7.5 vs. placebo 0.4 ± 6.8, p=0.467], fibrinogen [22.5 ± 77.8 vs. 10.0 ± 77.0, p=0.406], or leukocytes [0.2 ± 1.8 vs. 0.5 ± 1.8, p=0.560]). Chlorhexidine use decreased St. George's Respiratory Questionnaire scores compared to placebo (chlorhexidine -4.7 ± 8.0 vs. placebo 1.7 ± 8.9, p=0.032).

Interpretation: We did not detect a significant difference in microbiota biomass due to chlorhexidine use. Chlorhexidine decreased oral and sputum microbiota alpha diversity and improved respiratory health-related quality of life compared to placebo. Our results support the performance of a larger clinical trial.