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ObjectiveBronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O2) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology.MethodsChildren aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected.Results97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2 requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours.ConclusionAlthough a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O2 requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.

BackgroundBronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis.MethodsInfants aged ≤24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h.ResultsTwo hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: −6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: −8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p < 0.001), but had no significant effect upon virus detection rates.ConclusionDespite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis.Clinical trial registrationThe trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099.

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Indigenous Australian children hospitalised with bronchiolitis have significantly more severe illness than non-Indigenous children. Points of intervention that can address this and the identified high readmission rate (within 6 months) are required.

Airway pathologies have been comprehensively researched in adult asthma, but in children, the extent of airway inflammation associated with episodic wheeze, often diagnosed as asthma, has not been fully characterized. It is not clear whether persistent airway inflammation is present in the absence of wheezing symptoms, and there is controversy regarding the role of age and atopy. This study assessed cellular and cytokine markers of airway inflammation in asymptomatic children with a history of episodic wheeze. Children with a history of episodic wheeze and cough (study group) and nonasthmatic patients requiring elective surgery (control group) were recruited. All subjects in the study group had a history of significant episodic wheezing (>2 episodes per year), and used only as-needed beta-agonist treatment. Bronchoalveolar lavage (BAL) was obtained using bronchoscopic lavage (study group) and nonbronchoscopic lavage (control group). Differential cell counts of BAL and flow cytometry were performed to identify T-lymphocyte phenotypes, and intracellular cytokine profiles were measured after phorbol-12-myristate 13-acetate (PMA) stimulation of BAL fluid T-cells. Twenty-one children with a history of 2-12 episodes of wheeze per year and 21 nonasthmatic subjects without respiratory symptoms were recruited. Study and control subjects were matched for age (median age, 5 years) and demographic characteristics. Study subjects had higher IgE levels, but their measurements were still within normal range. No significant differences in BAL differential cell counts were noted, and in both groups, the majority of T-cells were CD3+ CD8+, with a median CD4:CD8 ratio of 0.6. There was no significant difference in T-cell expression of the activation markers HLA-DR and CD25 (IL-2 receptor), or in PMA-induced production of the intracellular cytokines IFN-gamma, IL-2, IL-4, IL-5, and IL-10. The results of this study suggest that significant T-cell-driven airway inflammation is absent in mild or nonatopic, asymptomatic children of this age group who have episodic wheeze. Our findings support asthma management guidelines that do not recommend long-term treatment of this group of patients with anti-inflammatory medications.

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There is a high rate of malnutrition among paediatric inpatients at DNH, consistent with results of anthropometric surveys in the newly independent East Timor. Despite the introduction of a standardized protocol following WHO guidelines and associated training on the management of severe malnutrition, the hospital case-fatality rate for severe malnutrition was still high (12.9%).