• Don Vicendese, Stephanie Yerkovich, Keith Grimwood, Patricia C Valery, Catherine A Byrnes, Peter S Morris, Shyamali C Dharmage, and Anne B Chang.
• Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia; School of Engineering and Mathematical Sciences, La Trobe University, Bundoora, VIC, Australia. Electronic address: don.vicendese@unimelb.edu.au.
• Chest. 2023 Jan 1; 163 (1): 526352-63.

BackgroundFollowing evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory 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 MethodsA secondary analysis was conducted of our previous randomized 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.ResultsAzithromycin 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).InterpretationRegular 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 unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice.Clinical Trials RegistrationAustralian New Zealand Clinical Trials Registry; ACTRN12610000383066.Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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