Azithromycin and childhood wheeze: Compelling biology, but does it translate into clinical benefit?

Wheezing illnesses are among the most common causes of respiratory morbidity and healthcare utilisation in childhood. Yet wheeze is a clinical symptom rather than a single disease process, arising from heterogeneous combinations of respiratory infection, airway inflammation, altered airway development and underlying susceptibility. This heterogeneity has complicated attempts to identify treatments that can be applied broadly across childhood wheezing disorders. Azithromycin is a particularly interesting example. Beyond its antimicrobial activity, it has well-recognised immunomodulatory effects on inflammatory cytokines, leukocyte recruitment and macrophage function. 1 Increasingly, however, clinical trial evidence challenges the assumption that demonstrating such biological effects necessarily predicts meaningful clinical benefit.