Effect of azithromycin on epithelial antiviral immunity in patients with asthma (AZIMUNE-study)

<bold>Background:</bold> Respiratory viral infections can significantly exacerbate asthma. Although azithromycin (AZM) reduces these episodes in asthmatic patients, its effects on epithelial immunity to viral infections are unknown. <bold>Objectives:</bold> To examine the effect of systemic AZM treatment on IFN-β protein and pro-inflammatory cytokine (IL-6) and chemokine (IL-8) expression in rhinovirus (RV1B)-challenged bronchial epithelial cells (BECs) of uncontrolled asthmatics with a history of exacerbation. <bold>Methods:</bold> In this double-blind randomized controlled trial (AZIMUNE), adults with uncontrolled asthma were treated with AZM or placebo for 12 weeks. Bronchoscopy was performed at baseline and week 12, and BECs were collected and cultured at baseline and week 12. BECs were then stimulated in vitro with Rhinovirus (RV1B). Protein quantification of IFN-β and pro-inflammatory cytokines and chemokines was measured after 48h post infection by MSD S-Plex and U-Plex before and after infection with RV1B. Wilcoxon signed-rank test was used for statistical analyses. <bold>Results:</bold> Thirty-two patients were analyzed for intention to treat where (n=16) received AZM and (n=16) received placebo. AZM treatment increased RV1B-induced expression of IFN-β protein 48h post infection (p=0.04). On the other hand, IL-6 (p=0.76) and IL-8 (p=0.49) levels did not change comparing before and after treatment with AZM or placebo (Figure 1A-C). <bold>Conclusions:</bold> Systemic treatment with AZM augments FN-β response of BECs to RV1B infection in patients with uncontrolled asthma. AZM did not alter RV1B-induced IL-6 and Il-8 expression.