Long-term Azithromycin in Children With Bronchiectasis Unrelated to Cystic Fibrosis Treatment Effects Over Time

BACKGROUND: Following evidence from randomized controlled trials, patients with bron-chiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respi-ratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown. RESEARCH QUESTIONS: (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects? STUDY DESIGN AND METHODS: A secondary analysis was conducted of our previous ran-domized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect. RESULTS: Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P < .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P < .001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P = .012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P = .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P = .012). INTERPRETATION: Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis un-related to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice.

Automated summary

This study aimed to determine the most effective period of azithromycin and explore factors that may modify its effects in patients with bronchiectasis unrelated to cystic fibrosis. The results showed that the most effective period of azithromycin was between weeks 17 and 62 after starting treatment. Additionally, factors such as nasopharyngeal carriage of bacterial pathogens, New Zealand children, and higher weight-for-height z scores were associated with greater reduction in exacerbations, while being born preterm was associated with lower reduction. These findings provide guidance for the treatment of patients with bronchiectasis unrelated to cystic fibrosis.