Azithromycin add-on therapy reduces airway inflammation and extracellular DNA: An AMAZES sub-study

Macrolide antibiotics have a range of immunomodulatory properties, which may influence clinical outcomes such as reduced exacerbations or attacks in patients with airways disease. While add-on azithromycin (AZM) reduces asthma attacks, the mechanisms remain unclear. We tested the hypothesis that add-on AZM therapy would reduce innate immune cytokines in sputum following 48 weeks of treatment. Induced sputum was collected at baseline and end of treatment from adults with symptomatic asthma in a randomized double-blind placebo controlled trial of oral AZM (500mg x 3 times weekly). Supernatant was assessed for IL-1β, IL-6, TNF-α and galectin-3 using ELISA and extracellular DNA (eDNA) using SYBR Green absorbance assay. Serum IL-6 was also assessed by ELISA. Despite no change in sputum cell counts, there were significantly lower levels of sputum IL-1β, TNF-α, IL-6 and eDNA following AZM therapy. This reduction was only observed in the non-eosinophilic participants with the exception of sputum IL-6, which was also reduced in those with eosinophilic asthma. Sputum galectin-3 and serum IL-6 were not altered with AZM therapy. AZM reduces innate immune inflammatory markers and eDNA but not systemic inflammation in poorly controlled asthma. Whether this is independent of changes in bacterial composition requires further study.