Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

Choroidal thickness in myopic and non-myopic children assessed with enhanced depth imaging optical coherence tomography

Purpose To examine choroidal thickness (ChT) and its topographical variation across the posterior pole in myopic and non-myopic children. Methods One hundred and four children aged 10-15 years of age (mean age 13.1 ± 1.4 years) had ChT measured using enhanced depth imaging optical coherence tomography (OCT). Forty one children were myopic (mean spherical equivalent -2.4 ± 1.5 D) and 63 non-myopic (mean +0.3 ± 0.3 D). Two series of 6 radial OCT line scans centred on the fovea were assessed for each child. Subfoveal ChT and ChT across a series of parafoveal zones over the central 6mm of the posterior pole were determined through manual image segmentation. Results Subfoveal ChT was significantly thinner in myopes (mean 303 ± 79 µm) compared to non-myopes (mean 359 ± 77 µm) (p<0.0001). Multiple regression analysis revealed both refractive error (r = 0.39, p<0.001) and age (r = 0.21, p = 0.02) were positively associated with subfoveal ChT. ChT also exhibited significant topographical variations, with the choroid being thicker in more central regions. The thinnest choroid was typically observed in nasal (mean 286 ± 77 µm) and inferior-nasal (306 ± 79 µm) locations, and the thickest in superior (346 ± 79 µm) and superior-temporal (341 ± 74 µm) locations. The difference in ChT between myopic and non-myopic children was significantly greater in central foveal regions compared to more peripheral regions (>3 mm diameter) (p<0.001). Conclusions Myopic children have significantly thinner choroids compared to non-myopic children of similar age, particularly in central foveal regions. The magnitude of difference in choroidal thickness associated with myopia appears greater than would be predicted by a simple passive choroidal thinning with axial elongation.