Effects of macrolides on airway microbiome and cytokine of children with bronchiolitis: A systematic review and meta-analysis of randomized controlled trials

Macrolides may attenuate airway inflammation of bronchiolitis with anti-inflammatory and antiviral effects. However, the potential mechanisms of action underlying the efficiency of macrolides in treating bronchiolitis are limited. Therefore, we performed a meta-analysis to assess the effects of macrolides on airway microbiome and cytokine of children with bronchiolitis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched until May 2018. The reference lists of included studies and pertinent reviews were investigated for supplementing our search. Randomized controlled trials (RCTs) that compared macrolides with placebo assessing the change of microbiome in airway and cytokine were included. A total of four RCTs were included in this review. Data analysis showed no significant reduction of viruses at 48 hr after azithromycin treatment (p = 0.41). There were significant reductions in Streptococcus pneumoniae (risk ratio [RR] 0.28, 95% confidence interval (CI) 0.14 to 0.6, p < 0.01), Haemophilus influenza (RR 0.35, 95% CI 0.2 to 0.62, p < 0.01), and Moraxella catarrhalis (RR 0.29, 95% CI 0.17 to 0.5, p < 0.01), but no significant reduction of Staphylococcus aureus (p = 0.28) following treatment with macrolides. There was a significant decrease in the serum interleukin-8(IL-8), interleukin-4(IL-4), and eotaxin levels following 3 weeks of clarithromycin therapy. There was no significant difference in the serum IL-8 level at Day 15 after the intervention between the azithromycin and control groups; however, a significant reduction of nasal lavage IL-8 level was found. The macrolides may reduce the IL-8 levels in the airway and plasma, but failed to demonstrate an antiviral effect in children with bronchiolitis.