Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease

Abstract

Rationale: Inflammation is now recognized as an integral part of the pathogenesis of chronic obstructive pulmonary disease (COPD). In contrast to the sterile airways of normal lungs, bacterial pathogens are often isolated from the airways in stable COPD. This "colonization" of the tracheobronchial tree, currently believed to be innocuous, could serve as an inflammatory stimulus, independent of current tobacco smoke exposure.

Objective: To test the hypothesis that bacterial colonization is associated with airway inflammation in stable COPD.

Methods: Bronchoscopy with bronchoalveolar lavage (BAL) was performed in three groups of subjects: 26 ex-smokers with stable COPD (COPD), 20 ex-smokers without COPD (ex-smokers), and 15 healthy nonsmokers (nonsmokers). Quantitative bacterial cultures, cell counts, chemokine, cytokine, proteinase/antiproteinase, and endotoxin levels in the BAL fluid were compared.

Results: Potentially pathogenic bacteria were recovered at > or = 100 cfu/ml in 34.6% of COPD, 0% of ex-smokers, and in 6.7% of nonsmokers (p = 0.003). All values are expressed as median (interquartile range). Subjects with colonized COPD had significantly greater relative (12.0 [28.4] vs. 3.0 [7.8]%, p = 0.03) and absolute (4.98 [5.26] x 10(4)/ml vs. 3.04 [2.82] x 10(4)/ml, p = 0.02) neutrophil counts, interleukin 8 (33.8 [189.8] vs. 16.9 [20.1] pg/ml, p = 0.005), active matrix metalloproteinase-9 (2.16 [4.30] vs. 0.84 [0.99] U/ml, p = 0.03), and endotoxin (36.0 [72.6] vs. 3.55 [7.17] mEU/ml, p = 0.004) levels in the BAL than the subjects with noncolonized COPD. These inflammatory constituents of BAL were also significantly elevated in subjects with colonized COPD when compared with ex-smokers and nonsmokers.

Conclusions: Bacterial colonization is associated with neutrophilic airway lumen inflammation in ex-smokers with COPD and could contribute to progression of airway disease in COPD.

Figure 1.

Comparison of bronchoalveolar lavage (BAL) fluid measurements among patients with chronic obstructive pulmonary disease (COPD) colonized (COPD, PPB+) and not colonized with potential pathogenic bacteria (COPD, PPB−), ex-smokers, and nonsmokers. The horizontal lines represent median values, the boxes represent 25th–75th quartiles, and the vertical lines represent 10th–90th percentile values. Significant differences between groups are represented by double-sided arrows with associated p values by Mann-Whitney U rank test. (A) Relative neutrophil count (PMN%); (B) absolute neutrophil count (PMN); (C) interleukin-8 (IL-8) level (pg/ml); (D) active matrix metalloproteinase-9 (MMP-9) level (U/ml); (E) endotoxin level (mEU/ml).

Figure 1.

Comparison of bronchoalveolar lavage (BAL) fluid measurements among patients with chronic obstructive pulmonary disease (COPD) colonized (COPD, PPB+) and not colonized with potential pathogenic bacteria (COPD, PPB−), ex-smokers, and nonsmokers. The horizontal lines represent median values, the boxes represent 25th–75th quartiles, and the vertical lines represent 10th–90th percentile values. Significant differences between groups are represented by double-sided arrows with associated p values by Mann-Whitney U rank test. (A) Relative neutrophil count (PMN%); (B) absolute neutrophil count (PMN); (C) interleukin-8 (IL-8) level (pg/ml); (D) active matrix metalloproteinase-9 (MMP-9) level (U/ml); (E) endotoxin level (mEU/ml).

Figure 1.

Comparison of bronchoalveolar lavage (BAL) fluid measurements among patients with chronic obstructive pulmonary disease (COPD) colonized (COPD, PPB+) and not colonized with potential pathogenic bacteria (COPD, PPB−), ex-smokers, and nonsmokers. The horizontal lines represent median values, the boxes represent 25th–75th quartiles, and the vertical lines represent 10th–90th percentile values. Significant differences between groups are represented by double-sided arrows with associated p values by Mann-Whitney U rank test. (A) Relative neutrophil count (PMN%); (B) absolute neutrophil count (PMN); (C) interleukin-8 (IL-8) level (pg/ml); (D) active matrix metalloproteinase-9 (MMP-9) level (U/ml); (E) endotoxin level (mEU/ml).