Abstract
Background: Respiratory exacerbations in children and adolescents with bronchiectasis are treated with antibiotics. However, antibiotics can have variable interindividual effects when treating exacerbations. Research Question: Can phenotypic features associated with symptom resolution after a 14-day course of oral antibiotics for a nonsevere exacerbation of bronchiectasis be identified? Study Design and Methods: Combining data from two multicenter randomized controlled trials, we identified 217 children with bronchiectasis assigned to at least 14 days of oral antibiotics to treat nonsevere (nonhospitalized) exacerbations. Univariable and then multivariable logistic regression were used to identify factors associated with symptom resolution within 14 days of commencing antibiotics. Identified associations were re-evaluated by mediation analysis. Results: Of the 217 study participants (52% male patients), 41% were Indigenous (Australian First Nations, New Zealand Māori, or Pacific Islander). The median age was 6.6 years (interquartile range, 4.0-10.1 years). By day 14, symptoms had resolved in 130 children (responders), but persisted in the remaining 87 children (nonresponders). Multivariable analysis found those who were Indigenous (adjusted OR [AOR], 3.59; 95% CI, 1.35-9.54) or showed new abnormal auscultatory findings (AOR, 3.85; 95% CI, 1.56-9.52) were more likely to be responders, whereas those with multiple bronchiectatic lobes at diagnosis (AOR, 0.66; 95% CI, 0.46-0.95) or higher cough scores when starting exacerbation treatment (AOR, 0.55; 95% CI, 0.34-0.90) were more likely to be nonresponders. Detecting a respiratory virus at the beginning of an exacerbation was not associated with antibiotic failure at 14 days. Interpretation: Children with Indigenous ethnicity, milder bronchiectasis, mild exacerbations (low reported cough scores), or new abnormal auscultatory signs are more likely to respond to appropriate oral antibiotics than those without these features. These patient and exacerbation phenotypes may assist clinical management and development of biomarkers to identify those whose symptoms are more likely to resolve after 14 days of oral antibiotics. Trial Registry: Australian New Zealand Clinical Trials Registry; Nos.: ACTRN12612000011886 and ACTRN12612000010897; URL: https://www.anzctr.org.au
| Original language | English |
|---|---|
| Pages (from-to) | 1378-1386 |
| Number of pages | 9 |
| Journal | Chest |
| Volume | 164 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 2023 |
Bibliographical note
Funding Information:The BEST-1 and BEST-2 were supported by the Australian National Health and Medical Research Council ( NHMRC ) [Grant 1019834] and the NHMRC Centre for Research Excellence ( CRE ) in Lung Health of Aboriginal and Torres Strait Islander Children [Grant GNT1040830]. A. B. C., K. G., I. B. M., and C. A. B. were the recipients of the original grants for the study. V. G. is supported by a Queensland Advancing Research Fellowship and a Royal Australasian College of Physicians’ Early Career Fellowship [Grant 2022REF00054]. J. M. M. is supported by the Lung Foundation Australia Hope Research Fund Andrew Harrison Fellowship in Bronchiectasis Research 2021 and the NHMRC CRE [Grant GNT1040830]. A. B. C. is supported by an NHMRC practitioner fellowship [Grant 1058213]. A. B. C. and K. G. report multiple grants from NHMRC and the Australian Medical Research Futures Fund. C. A. B. is supported by the Health Research Council ( HRC ) of New Zealand [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); health care delivery study [Grant HRC 20/1184; payment to institution]; and prevention of recurrent respiratory-related hospitalizations in young children [Grant APP1157228; payment to institution].
Publisher Copyright:
© 2023 American College of Chest Physicians