Effect of levofloxacin on neutrophilic airway inflammation in stable COPD: a
randomized, double-blind, placebo-controlled trial.
Author(s): Siva R(1), Bafadhel M(2), Monteiro W(3), Brightling CE(3), Pavord ID(2).
Affiliation(s): Author information:
(1)Department of Respiratory Medicine, Croydon University Hospital, Croydon Health
Services NHS Trust, London, UK.
(2)Department of Respiratory Medicine, Nuffield Department of Clinical Medicine,
University of Oxford, Old Road Campus, Oxford, UK.
(3)Institute for Lung Health, NIHR Respiratory Biomedical Research Unit, Department
of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Publication date & source: 2014, Int J Chron Obstruct Pulmon Dis. , 9:179-86
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.
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