Elimination of colonizing bacterial pathogens with antibiotics decreases airway inflammation in COPD

Purpose: 'Colonization' of the lower respiratory tract by pathogenic bacteria could contribute to airway inflammation in COPD. Antibiotics that eliminate such 'colonization' should decrease airway inflammation. To test this hypothesis, we measured inflammatory markers in sputum obtained from patients with stable COPD, before and after a course of oral antibiotics. Methods: Eleven patients with COPD were studied every two weeks for four visits. At each visit, clinical evaluation and spirometry were performed, and sputum for culture and measurement of IL-8, TNF α and Elastase activity was collected. In between the second and third visit, 6 patients received oral Ciprofloxacin 750mg bid for 10 days, and five patients received oral Clarithromycin 500mg bid for 10 days Results: Eight patients had a positive sputum culture for pathogenic bacteria (nontypeable Haemophilus influenzae in 6, Moraxella catarrhalis in 1, and both in 1) at the second visit prior to antibiotic therapy. Of these 8 patients, all 4 in the Ciprofloxacin group (100%) and 2 of the 4 in the Clarithromycin group (50%) had a bacteriologic response (negative sputum culture on third visit). Patients who had a bacteriologic response demonstrated a significant decrease in sputum IL-8 after antibiotics (7123pg/ml before vs 1971pg/ml after antibiotics, p=0.01). TNF α and sputum elastase also decreased after antibiotics but the changes were not statistically significant. In the four patients who either had no pathogens prior to antibiotics (2) or were bacteriologic failures (2), there was no significant change in their sputum IL-8 (3305 pg/ml before vs 2330 pg/ml after antibiotics), TNF α or elastase levels. Conclusions: Ciprofloxacin was more effective than Clarithromycin in sterilising sputum in stable COPD. Sputum IL-8 decreased significantly with elimination of bacterial pathogens, supporting the hypothesis that bacterial 'colonization' contributes to airway inflammation in COPD. Clinical Implications: Tracheobronchial bacterial colonization, by inciting airway inflammation, may contribute to the progression of COPD.