Azithromycin therapy in infants hospitalized for RSV bronchiolitis: airway MMP-9 levels and subsequent recurrent wheeze

BACKGROUND:Early-life RSV bronchiolitis is a significant risk factor for childhood asthma. In-vitro and in-vivo studies suggested that decreasing airway matrix metalloprotease (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. OBJECTIVE:We aimed to investigate if azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, if upper airway MMP-9 levels correlate with upper airway IL-8 levels, and whether MMP-9 levels reduction is associated with reduced post-RSV recurrent wheeze (RW). METHODS:Two hundred otherwise healthy 1-18 month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10mg/kg daily for seven days followed by 5mg/kg daily for seven days) or placebo. Infants were followed for 2-4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of study treatment), and six months later. RESULTS:Upper airway MMP-9 levels were highly correlated with IL-8 levels at all three-time points: randomization, day 14, and six months (r=0.80; p<0.0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (p=0.0085), but no longer different six months later. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (p=0.49, 0.39, respectively). CONCLUSION:Azithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV.