Abstract
Background: Following 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 Methods: A 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. 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 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 Registration: Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.
| Original language | English |
|---|---|
| Pages (from-to) | 52-63 |
| Number of pages | 12 |
| Journal | Chest |
| Volume | 163 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2023 |
Bibliographical note
Funding Information:Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. V. is a member of a DSMB on The Palace Study at Austin Health on penicillin allergy (no payment). K. G. holds the following Australian National Health and Medical Research Council (NHMRC) project grants: 1157228, for a randomized control trial (RCT) on azithromycin and preventing acute respiratory illness in high-risk infants (payment to institution); 1169868, for an RCT on azithromycin and mucolytics in primary ciliary dyskinesia (payment to institution); 2014419, for an RCT on azithromycin and mucolytics in bronchiectasis (payment to institution). He is a member of a DSMB for an NHMRC-funded RCT for azithromycin in labor (no payment). C. A. B. holds the following grants: Health Research Council (HRC) of New Zealand feasibility grant HRC 21/166 for the development of study in bronchiectasis (payment to institution); ‘Flu Lab’ not-for-profit organization for viral study (payment to institution); HRC 20/1184 Health care delivery study (payment to institution); APP1157228 Prevention of recurrent respiratory-related hospitalizations in young children (payment to institution). She is a trustee of the Bronchiectasis Foundation (no payment) and chairs the Clinical Advisory Panel for Cystic Fibrosis (no payment). S. C. D. holds: an NHMRC Investigator Grant (payment to institution); an NHMRC Cohort Grant (payment to institution); Investigator Initiated Grant from Global GSK (payment to institution). She is a member of Lancet Respiratory Medicine International Advisory Board (no payment); Australian Institute of Health and Welfare Chronic Respiratory Disease Advisory Board (no payment); Asthma Foundation Research Committee (no payment); Editorial Board of Clinical and Experimental Allergy (no payment). A. B. C. holds the following NHMRC project grants: 1157228, for an RCT on azithromycin and preventing acute respiratory illness in high-risk infants (payment to institution); 1169868, for an RCT on azithromycin and mucolytics in primary ciliary dyskinesia (payment to institution); 2014419, for an RCT on azithromycin and mucolytics in bronchiectasis (payment to institution). She has received royalties from Up-to-Date, for chapters on cough and bronchiectasis (personal payment); BMJ Evidence for asthma (payment to institution). She is a member of a DSMB for unlicensed vaccines (GSK, AZ, and Moderna) (payment to institution). She is a member of NHMRC Health Impact Committee (no payment); NHMRC Women in Science (no payment); and ERS Guideline Committee (no payment). None declared (S. Y., P. C. V., P. S. M.).
Funding Information:
Funding/support: This study was supported by the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in paediatric bronchiectasis grant 1170958. A. B. C. and S. C. D. are supported by NHMRC fellowships. D. V. and S. Y. are funded by the NHMRC Centre of Research Excellence in bronchiectasis. A. B. C. is also supported by the Children’s Hospital Foundation. The original Bronchiectasis Intervention Study was supported by the NHMRC project grant 389837 and the New Zealand Health Research Council project grant 08/158.
Funding Information:
Author contributions: Study concept and design: D. V. A. B. C. K. G. S. C. D. Data collection and collation: A. B. C. P. C. V. S. T. Y. C. B. Data verification: P. C. V. S. T. Y. D. V. Statistical analysis and interpretation: D. V. S. C. D. Drafting of the manuscript: D. V. A. B. C. S. C. D. Input to the manuscript: all. Funding/support: This study was supported by the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in paediatric bronchiectasis grant 1170958. A. B. C. and S. C. D. are supported by NHMRC fellowships. D. V. and S. Y. are funded by the NHMRC Centre of Research Excellence in bronchiectasis. A. B. C. is also supported by the Children's Hospital Foundation. The original Bronchiectasis Intervention Study was supported by the NHMRC project grant 389837 and the New Zealand Health Research Council project grant 08/158. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. V. is a member of a DSMB on The Palace Study at Austin Health on penicillin allergy (no payment). K. G. holds the following Australian National Health and Medical Research Council (NHMRC) project grants: 1157228, for a randomized control trial (RCT) on azithromycin and preventing acute respiratory illness in high-risk infants (payment to institution); 1169868, for an RCT on azithromycin and mucolytics in primary ciliary dyskinesia (payment to institution); 2014419, for an RCT on azithromycin and mucolytics in bronchiectasis (payment to institution). He is a member of a DSMB for an NHMRC-funded RCT for azithromycin in labor (no payment). C. A. B. holds the following grants: Health Research Council (HRC) of New Zealand feasibility grant HRC 21/166 for the development of study in bronchiectasis (payment to institution); ‘Flu Lab’ not-for-profit organization for viral study (payment to institution); HRC 20/1184 Health care delivery study (payment to institution); APP1157228 Prevention of recurrent respiratory-related hospitalizations in young children (payment to institution). She is a trustee of the Bronchiectasis Foundation (no payment) and chairs the Clinical Advisory Panel for Cystic Fibrosis (no payment). S. C. D. holds: an NHMRC Investigator Grant (payment to institution); an NHMRC Cohort Grant (payment to institution); Investigator Initiated Grant from Global GSK (payment to institution). She is a member of Lancet Respiratory Medicine International Advisory Board (no payment); Australian Institute of Health and Welfare Chronic Respiratory Disease Advisory Board (no payment); Asthma Foundation Research Committee (no payment); Editorial Board of Clinical and Experimental Allergy (no payment). A. B. C. holds the following NHMRC project grants: 1157228, for an RCT on azithromycin and preventing acute respiratory illness in high-risk infants (payment to institution); 1169868, for an RCT on azithromycin and mucolytics in primary ciliary dyskinesia (payment to institution); 2014419, for an RCT on azithromycin and mucolytics in bronchiectasis (payment to institution). She has received royalties from Up-to-Date, for chapters on cough and bronchiectasis (personal payment); BMJ Evidence for asthma (payment to institution). She is a member of a DSMB for unlicensed vaccines (GSK, AZ, and Moderna) (payment to institution). She is a member of NHMRC Health Impact Committee (no payment); NHMRC Women in Science (no payment); and ERS Guideline Committee (no payment). None declared (S. Y. P. C. V. P. S. M.). Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript, or any other role beyond financial support. Other contributions: We thank the research coordinators and nurses of the Bronchiectasis Intervention Study who helped to acquire data for the RCT. Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data are not available. Don Vicendese, Stephanie Yerkovich, and Patricia C. Valery are the guarantors of the content of the manuscript, including the data and analysis. Additional information: The e-Appendix and e-Figures are available online under “Supplementary Data.”
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