A collaborative and international study of bronchiectasis in Indigenous children

Aboriginal children have repeated pneumonia episodes; some get better while others develop bronchiectasis (a chronic lung disease). The risk factors associated with progression to bronchiectasis, and the natural history of bronchiectasis in this population is little known. Given the similarities of these diseases among indigenous populations of affluent countries and to increase study size, a collaborative and international study of Indigenous children (Aboriginal and Torres Strait Islander, New Zealand Maori or Pacific Islander and Alaskan Native) has been initiated. We plan to follow up Aboriginal children aged 12 months to 8 years diagnosed with bronchiectasis or chronic moist cough. For those diagnosed with bronchiectasis, after fully informed consent is obtained from the parent(s), the child will be allocated by chance to one of the 2 treatment regimes: (1) Azithromycin nce/week or (2) placebo once/week. Children will receive the medication or the placebo for a period of 24 months. All these children will be clinically seen 2x/year by the study's paediatrician and 2x/year by the research nurse for the duration of the study. The study size and study power calculations were based on our Central Australia data (Valery et al, Paed Inf Dis J, 2004) where Indigenous children diagnosed with bronchiectasis had on average 1 hospitalised episode of pulmonary exacerbation every 6 months (standard deviation=5.4), so the ‘placebo’ group is expected to have 4 episodes during a 24-months follow-up. Assuming we will follow these children for 24 months, if intervention is effective, assuming 50% reduction in the number of pulmonary exacerbation, the intervention group is expected to have 2 episodes vs. 3.4 episodes for the ‘placebo’ group (assuming we have 15% reduction in the placebo group as well due to better medical care due to the study) we have 95% power with 51 children in each group. Importantly, these estimates used hospitalised exacerbation rates as a conservative estimate of total exacerbation rates. In fact, if we determine the sample size required to estimate the difference between the rate parameters of two Poisson distributions over 24 months, 34 observations from each sample (68 child years at risk) are required to have a 90% chance of rejecting the null hypothesis when the true difference over 2 years equals 1.7 using a two-sided test (www.statlets.com/sample_size_rates.htm). By documenting, for the first time, the epidemiology and natural history of children with chronic moist cough and bronchiectasis, the study will provide a much-needed rationale for their management. If we can scientifically show that this is true, that Azithromycin is effective in reducing the number of respiratory infections, this would be an achievable advance in the treatment "in the field" for these children.