Microbiologic Determinants of Exacerbation in Chronic Obstructive Pulmonary Disease

Abstract

Background The culture of bronchial secretions from the lower airway has been reported to be positive for potentially pathogenic microorganisms (PPMs) in patients with stable chronic obstructive pulmonary disease (COPD), but the determinants and effects of this bacterial load in the airway are not established. Methods To determine the bronchial microbial pattern in COPD and its relationship with exacerbation, we pooled analysis of crude data from studies that used protected specimen brush sampling, with age, sex, smoking, lung function, and microbiologic features of the lower airway as independent variables and exacerbation as the outcome, using logistic regression modeling. Results Of 337 study participants, 70 were healthy, 181 had stable COPD, and 86 had exacerbated COPD. Differences in the microbial characteristics in the participating laboratories were not statistically significant. A cutoff point of 10² colony-forming units (CFU) per milliliter or greater for the identification of abnormal positive culture results for PPMs was defined using the 95th percentile in the pooled analysis of healthy individuals. Bronchial colonization of 10² CFU/mL or greater by PPMs was found in 53 patients with stable COPD (29%) and in 46 patients with exacerbated COPD (54%) (P<.001, χ² test), with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher microbial loads were associated with exacerbation and showed a statistically significant dose-response relationship after adjustment for covariates (odds ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a statistically significant risk factor after adjustment for microbial load (odds ratio, 11.12; 95% confidence interval, 1.17-105.82). Conclusions One quarter of the patients with COPD are colonized by PPMs during their stable periods. Exacerbation is associated with the overgrowth of PPMs and with the appearance of P aeruginosa in the lower airway, which is associated with exacerbation symptoms independent of load.