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

J Allergy Clin Immunol. 2015 May;135(5):1171-8.e1. doi: 10.1016/j.jaci.2014.10.001. Epub 2014 Nov 18.

Abstract

Background: Respiratory syncytial virus (RSV) bronchiolitis in infancy is a major risk factor for recurrent wheezing and asthma. Because azithromycin attenuated neutrophilic airway inflammation in a murine viral bronchiolitis model, demonstration of similar effects in human subjects might provide a strategy for the prevention of postbronchiolitis recurrent wheezing.

Objectives: We sought to investigate whether azithromycin treatment during RSV bronchiolitis reduces serum and nasal lavage IL-8 levels and the occurrence of postbronchiolitis recurrent wheezing.

Method: We performed 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 fluid 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 with placebo, azithromycin treatment did not reduce serum IL-8 levels at day 8 (P = .6) but resulted in a greater decrease in nasal lavage fluid IL-8 levels by day 15 (P = .03). Twenty-two percent of azithromycin-treated participants experienced at least 3 wheezing episodes compared with 50% of participants in the placebo group (P = .07). Azithromycin treatment resulted in prolonged time to the third wheezing episode (P = .048) and in fewer days with respiratory symptoms over the subsequent year in comparison with placebo (36.7 vs 70.1 days, P = .01).

Conclusion: In this proof-of-concept study azithromycin treatment during RSV bronchiolitis reduced upper airway IL-8 levels, prolonged the time to the third wheezing episode, and reduced overall respiratory morbidity over the subsequent year.

Keywords: Azithromycin; IL-8; respiratory syncytial virus; wheezing.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azithromycin / administration & dosage
  • Azithromycin / therapeutic use*
  • Bronchiolitis, Viral / blood
  • Bronchiolitis, Viral / complications
  • Bronchiolitis, Viral / drug therapy*
  • Bronchiolitis, Viral / metabolism*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukin-8 / blood
  • Interleukin-8 / metabolism*
  • Male
  • Nasal Lavage Fluid
  • Respiratory Sounds / drug effects*
  • Respiratory Sounds / etiology
  • Respiratory Syncytial Virus Infections / blood
  • Respiratory Syncytial Virus Infections / complications
  • Respiratory Syncytial Virus Infections / drug therapy*
  • Respiratory Syncytial Virus Infections / metabolism*
  • Respiratory Syncytial Virus, Human*
  • Risk Factors
  • Treatment Outcome

Substances

  • Interleukin-8
  • Azithromycin