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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. (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects? 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. 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). 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. Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. [ABSTRACT FROM AUTHOR]

Objective: The sole prospective longitudinal study of children with either chronic suppurative lung disease (CSLD) or bronchiectasis published in the current era was limited to a single center. We sought to extend this study by evaluating the longer-term clinical and lung function outcomes and their associated risk factors in Indigenous children of adolescents from Australia, Alaska, and New Zealand who participated in our previous CSLD or bronchiectasis studies during 2004-2010., Methods: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans., Results: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values., Conclusion: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed., (© 2020 Wiley Periodicals, Inc.)

Objective: Indigenous children in developed countries are at increased risk of chronic suppurative lung disease (CSLD), including bronchiectasis. We evaluated sociodemographic and medical factors in indigenous children with CSLD/bronchiectasis from Australia, United States (US), and New Zealand (NZ)., Methods: Indigenous children aged 0.5-8 years with CSLD/bronchiectasis were enrolled from specialist clinics in Australia (n = 97), Alaska (n = 41), and NZ (n = 42) during 2004-2009, and followed for 1-5 years. Research staff administered standardized parent interviews, reviewed medical histories and performed physical examinations at enrollment., Results: Study children in all three countries had poor housing and sociodemographic circumstances at enrollment. Except for increased household crowding, most poverty indices in study participants were similar to those reported for their respective local indigenous populations. However, compared to their local indigenous populations, study children were more often born prematurely and had both an increased frequency and earlier onset of acute lower respiratory infections (ALRIs). Most (95%) study participants had prior ALRI hospitalizations and 77% reported a chronic cough in the past year. Significant differences (wheeze, ear disease and plumbed water) between countries were present., Discussion: Indigenous children with CSLD/bronchiectasis from three developed countries experience significant disparities in poverty indices in common with their respective indigenous population; however, household crowding, prematurity and early ALRIs were more common in study children than their local indigenous population. Addressing equity, especially by preventing prematurity and ALRIs, should reduce risk of CSLD/bronchiectasis in indigenous children., (© 2013 Wiley Periodicals, Inc.)

Background: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis., Methods/design: We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV(1); for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms., Discussion: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.