The Effect of Azithromycin in Adults with Stable Neutrophilic COPD: A Double Blind Randomised, Placebo Controlled Trial

Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive airway disease characterised by airway inflammation or bronchitis. Neutrophilic bronchitis is associated with both bacterial colonisation and lung decline and is common in exacerbations of COPD. Despite current available therapies to control inflammation, bronchitis remains common. This study tested the hypothesis that azithromycin treatment, as an add-on to medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8) levels, as well as load. We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable bronchitis. Methods: Eligible participants (n = 30) were randomised to azithromycin 250 mg daily or placebo for 12 weeks in to their standard respiratory medications. Sputum was induced at screening, randomisation and monthly for a 12 treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment. bacteriology was assessed in sputum samples at randomisation and the end of treatment visit. Severe exacerbations symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and weeks following treatment. A sub-group of participants underwent chest computed tomography scans (n = 15). Results: Nine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the bacterial load of all participants was 5.22 x 10(7) cfu/mL. Azithromycin treatment resulted in a non-significant sputum neutrophil proportion, CXCL8 levels and bacterial load. The mean severe exacerbation rate was 0.33 per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence (95%CI): 0.37 (0.11,1.21), p = 0.062). For participants who underwent chest CT scans, no alterations were observed. Conclusions: In stable COPD with neutrophilic bronchitis, add-on azithromycin therapy showed a trend to reduced exacerbations sputum neutrophils, CXCL8 levels and bacterial load. Future studies with a larger sample size are warranted.