Randomized trial to evaluate azithromycin's effects on serum and upper airway IL-8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis

Abstract

Background Respiratory syncytial virus (RSV) bronchiolitis in infancy is a major risk factor for recurrent wheezing and asthma. As azithromycin attenuated neutrophilic airway inflammation in a murine viral bronchiolitis model, demonstration of similar effects in humans may provide a strategy for the prevention of post-bronchiolitis recurrent wheezing. Objectives To investigate whether azithromycin treatment during RSV bronchiolitis reduces serum and nasal lavage IL-8 levels and the occurrence of post-bronchiolitis recurrent wheezing. Method A randomized, double-masked, placebo-controlled, proof-of-concept trial in 40 otherwise healthy infants hospitalized with RSV bronchiolitis who were treated with azithromycin or placebo for 14 days. IL-8 levels were measured in nasal lavage and serum on randomization, day 8, and day 15 (nasal lavage only). The occurrence of wheezing episodes was assessed monthly over the ensuing 50 weeks. Results Compared to placebo, azithromycin treatment did not reduce serum IL-8 levels at day 8 (p=0.6), but resulted in a greater decline in nasal lavage IL-8 by day 15 (p=0.03). 22% of azithromycin-treated participants experienced at least 3 wheezing episodes compared to 50% of participants in the placebo group (p=0.07). Azithromycin treatment resulted in prolonged time to the third wheezing episode (p=0.048), and in fewer days with respiratory symptoms over the subsequent year in comparison to placebo (36.7 vs. 70.1 days; p=0.01). Conclusion In this proof-of-concept study, azithromycin treatment during RSV bronchiolitis reduced upper airway IL-8 levels, prolonged the time to a third wheezing episode, and reduced overall respiratory morbidity over the subsequent year.

Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses

“…Viral infections are associated with neutrophilic airway inflammation and increased expression of the dominant neutrophil chemoattractant IL - 8, 23,24 and azithromycin has recently been demonstrated to reduce IL-8 levels in nasal secretions during respiratory syncytial virus bronchiolitis. 25 However, although polymorphisms in the IL-8 gene also have been shown to modulate IL-8 production, 11 we did not observe a significant interaction between reduced risk of progressing to severe LRTI and the IL-8 rs4073 polymorphism.…”

Azithromycin therapy during respiratory syncytial virus bronchiolitis: Upper airway microbiome alterations and subsequent recurrent wheeze

“…1,2 We recently reported that, in a proof-of-concept randomized trial (the Azithromycin to Prevent Wheezing following RSV Bronchiolitis trial), azithromycin (AZM) therapy during RSV bronchiolitis reduced the probability of developing RW during the subsequent year by approximately 50%. 3 AZM was chosen because it is capable of targeting neutrophilic airway inflammation 4 and based on our results in a mouse model of viral bronchiolitis. 5 In infants hospitalized with RSV bronchiolitis, we demonstrated anti-inflammatory effects of AZM 3 reflected by reduced nasal lavage levels of IL-8, a marker of neutrophilic airway inflammation.…”

“…3 AZM was chosen because it is capable of targeting neutrophilic airway inflammation 4 and based on our results in a mouse model of viral bronchiolitis. 5 In infants hospitalized with RSV bronchiolitis, we demonstrated anti-inflammatory effects of AZM 3 reflected by reduced nasal lavage levels of IL-8, a marker of neutrophilic airway inflammation. However, the mechanism of AZM's anti-inflammatory effects may have reflected direct effects on the immune response, or an indirect effect through antibacterial actions of AZM leading to alteration in bacteria abundance and a reduction in neutrophilic inflammation.…”

Eosinophil cationic protein mRNA expression in children with bronchial asthma

“…ECP is a specific marker of eosinophils (Ursaciuc et al, 2010;Shah et al, 2012;Beigelman, 2014;Smith et al, 2015), which is mainly activated and released by eosinophils and causes neurotoxicity and cytotoxicity. In addition, ECP induces release of histamine by mast cells, causing airway hyperresponsiveness, resulting in bronchial asthma attack (Reed et al, 2007;Choi et al, 2010;Chua et al, 2010;Ursaciuc et al, 2010;Wei et al, 2010;Braga et al, 2011;Olive et al, 2011).…”