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Randomized Controlled Trial
. 2014 Feb 7:9:179-86.
doi: 10.2147/COPD.S55419. eCollection 2014.

Effect of levofloxacin on neutrophilic airway inflammation in stable COPD: a randomized, double-blind, placebo-controlled trial

Roshan Siva  1 , Mona Bafadhel  2 , William Monteiro  3 , Christopher E Brightling  3 , Ian D Pavord  2
Affiliations
Randomized Controlled Trial

Effect of levofloxacin on neutrophilic airway inflammation in stable COPD: a randomized, double-blind, placebo-controlled trial

Roshan Siva et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Rationale: Airway inflammation persists after smoking cessation in established chronic obstructive pulmonary disease (COPD), suggesting that other factors drive the airway inflammatory response.

Objectives: We tested the hypothesis that high levels of bacterial colonization are associated with increased levels of neutrophilic airway inflammation in stable COPD by examining the cross-sectional relationship between these measurements and by conducting a randomized, double-blind, placebo-controlled study of the effect of levofloxacin in patients with stable COPD.

Methods: Patients were randomized to receive either levofloxacin 500 mg daily or placebo for 7 days and underwent sputum induction for a differential cell count and quantitative bacterial analysis at baseline and at days 7, 14, and 28.

Results: Sputum percentage neutrophil count correlated with airway bacterial load at baseline (r=0.56; P=0.003). Levofloxacin reduced bacterial load compared with placebo by 4.9-fold (95% confidence interval, 1.4-25.7; P=0.02) at day 7 but had no effect at any point on any marker of neutrophilic airway inflammation. In patients with a baseline bacterial load of more than 10(6) cfu/mL, levofloxacin treatment was associated with a 26.5% (95% confidence interval, 1.8%-51.3%; P=0.04) greater reduction in the percentage neutrophil count compared with placebo at day 7. Change in percentage neutrophil count correlated significantly with baseline airway bacterial load and change in airway bacterial load.

Conclusion: In stable COPD, levofloxacin treatment causes a short-term reduction in bacterial load. This is associated with a reduction in neutrophilic airway inflammation in patients with high bacterial loads. Further studies are required to investigate whether this effect is clinically advantageous.

Keywords: antibiotics; bacteria; sputum.

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Figures

Figure 1
Figure 1
Assessments at each visit: pre- and postbronchodilator spirometry, sputum induction, and symptoms.
Figure 2
Figure 2
Relationship between airway bacterial load and percentage neutrophil count at baseline. Notes: r=0.56; P=0.003. Abbreviations: O, nonsignificant growth; X, potentially pathogenic microorganisms.
Figure 3
Figure 3
Change in percentage neutrophil count in patients with airway bacterial load of more than 106 cfu/mL. Notes: Data presented as mean (standard error of the mean). Open circles represent placebo, closed circles represent levofloxacin. Abbreviation: SEM, standard error of the mean.
Figure 4
Figure 4
Mean change in percentage neutrophil count after (A) placebo and (B) levofloxacin, according to log baseline airway bacterial load. Abbreviations: O, nonsignificant growth; X, potentially pathogenic microorganism.
See this image and copyright information in PMC

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