Azithromycin for acute wheezing and bronchiolitis in children younger than six years: a systematic review and meta-analysis

We further hypothesize that any apparent benefit observed in specific contexts is driven not by the drug itself but by care setting and patient phenotype. Specifically, we postulate that azithromycin's anti-inflammatory properties may reduce symptoms in intensive care settings with high-acuity respiratory failure or in home-managed recurrent episodes, but not in standard acute care for viral bronchiolitis.

The mechanistic rationale rests on macrolide anti-inflammatory activity: inhibition of NF-κB signaling, reduction of pro-inflammatory cytokines (IL-8, TNF-α, MCP-1), and enhancement of airway epithelial barrier function. However, the translation of in vitro anti-inflammatory efficacy to clinical benefit in real patients depends critically on patient phenotype and disease severity. We predicted that high-inflammation phenotypes (PICU respiratory failure, recurrent post-viral wheezing) would demonstrate benefit, while unselected acute presentations would not.