The effect of oral clarithromycin on bronchial airway inflammation in moderate-to-severe stable COPD: a randomized controlled trial.
BACKGROUND
COPD is characterized by bronchial neutrophilic inflammation. Clarithromycin is a macrolide antibiotic that has antibacterial and anti-inflammatory properties. Macrolide antibiotics have been shown to improve airway inflammation in diffuse pan-bronchiolitis but their role in COPD is undetermined. The aim of the study was to determine if 3 months of therapy with modified-release oral clarithromycin (Klaricid XL) 500 mg/day reduced bronchial airway inflammation in patients with moderate-to-severe stable COPD compared with placebo.


METHODS
A prospective, double-blind controlled trial randomized patients with moderate-to-severe stable COPD to 3 months' therapy with oral modified-release clarithromycin 500 mg/day or placebo. Patients underwent saline sputum induction before and after treatment with clarithromycin. The effects of clarithromycin on sputum total cell and neutrophil counts, supernatant interleukin-8 (IL-8), leukotriene B(4) (LTB(4)), tumor necrosis factor (TNF)-alpha, neutrophil elastase (NE), and neutrophil chemotaxis were assessed in comparison with placebo.


RESULTS
Of a total of 67 patients included in the trial, 31 were treated with clarithromycin and 36 with placebo. The groups were similar in age, body mass index, history of smoking, and spirometry. Of 60 evaluable patients, 26 and 34 completed 3 months' therapy with clarithromycin and placebo, respectively. Clarithromycin had no significant effect on sputum total cell count, neutrophil count, IL-8, LTB(4), TNFalpha levels or neutrophil elastase. However, clarithromycin did cause a small reduction in the neutrophil differential (p = 0.04 relative to placebo) and neutrophil chemotaxis (p = 0.058 relative to placebo).


CONCLUSIONS
Oral clarithromycin 500 mg/day administered for 3 months had no significant effect on sputum neutrophil numbers or cytokine levels in patients with moderate-to-severe stable COPD. However, clarithromycin did cause a small reduction in the neutrophil differential and neutrophil chemotaxis. Further studies may be warranted to determine the clinical significance of these findings.
Banerjee
Dev
D
Department of Respiratory Medicine, City Hospital, Birmingham, UKDepartment of Respiratory Medicine, Birmingham Heartlands Hospital, Birmingham, UK.
Honeybourne
David
D
Khair
Omer A
OA
D000284:Administration, Oral; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D017291:Clarithromycin / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003692:Delayed-Action Preparations; D017291:Clarithromycin