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

Description

This meta-analysis tests a primary hypothesis that azithromycin offers no meaningful clinical benefit for acute wheezing and bronchiolitis in young children when prescribed in routine clinical settings (emergency departments and general hospital wards). 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.

Steps to reproduce

1. Download Analysis - PPR.qmd and DADOS_FINAIS_10ensaios.xlsx; place in same folder. 2. Install R (https://www.r-project.org) and RStudio (https://www.rstudio.com). 3. In RStudio Console, run: install.packages("meta"); install.packages("readxl") 4. Open Analysis - PPR.qmd in RStudio. 5. Click "Render" button. 6. HTML report generates automatically with Table 1 and 5 forest plots (Figures 1, 1S, 2, 3, 4). 7. PNG and PDF figures saved in output/ folder. 8. To update: edit data in Excel, re-render document.

Institutions

• Universidade Federal de São Paulo

  São Paulo, São Paulo

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