Comparison of Profiles of First Nations and Non-First Nations Children With Bronchiectasis Over Two 5-Year Periods in the Northern Territory, Australia.

BACKGROUND: Although the burden of bronchiectasis is recognized globally, pediatric data are limited, particularly on trends over the years. Also, no published data exists regarding whether vitamin D deficiency or insufficiency and human T-cell lymphotropic virus type 1 (HTLV-1) infection, both found to be related to severe bronchiectasis in First Nations adults, also are important in children with bronchiectasis. RESEARCH QUESTION: Among children with bronchiectasis, (1) have the clinical and BAL profiles changed between two 5-year periods (period 1, 2007-2011; period 2, 2012-2016) and (b) are vitamin D deficiency or insufficiency, HTLV-1 infection, or both associated with radiologic severity of bronchiectasis? STUDY DESIGN AND METHODS: We analyzed the data from children with bronchiectasis prospectively enrolled at Royal Darwin Hospital, Australia, at the first diagnosis; that is, no child was included in both periods. Data collected include demographics, BAL, routine investigation bloods, and high-resolution CT scan of the chest evaluated using the Bhalla and modified Bhalla scores. RESULTS: The median age of the 299 children was 2.2 years (interquartile range, 1.5-3.7 years). One hundred sixty-eight (56%) were male and most were First Nations (92%). Overall, bronchiectasis was high over time, particularly among First Nations children. In the later period, numbers of non-First Nations children more than tripled, but did not reach statistical significance. In period 2 compared with period 1, fewer First Nations children demonstrated chronic cough (period 1, 61%; period 2, 47%; P = .03), and were younger, First Nations children were less likely to have received azithromycin (period 1, 42%; period 2, 21%; P < .001), and the BAL fluid of First Nations children showed lower Haemophilus influenzae and Moraxella catarrhalis infection. HTLV-1 infection was not detected, and vitamin D deficiency or insufficiency did not correlate with severity of bronchiectasis. INTERPRETATION: Bronchiectasis remains high particularly among First Nations children. Important changes in their profiles that arguably reflect improvements were present, but overall, the profiles remained similar. Although vitamin D deficiency was uncommon, its role in children with bronchiectasis requires further evaluation. HTLV-1 infection was nonexistent and is unlikely to play any role in First Nations children with bronchiectasis.

Do combined upper airway cultures identify lower airway infections in children with chronic cough?

BACKGROUND: Obtaining lower airway specimens is important for guiding therapy in chronic lung infection but is difficult in young children unable to expectorate. While culture-based studies have assessed the diagnostic accuracy of nasopharyngeal or oropharyngeal specimens for identifying lower airway infection, none have used both together. We compared respiratory bacterial pathogens cultured from nasopharyngeal and oropharyngeal swabs with bronchoalveolar lavage (BAL) cultures as the "gold standard" to better inform the diagnosis of lower airway infection in children with chronic wet cough. METHODS: Nasopharyngeal and oropharyngeal swabs and BAL fluid specimens were collected concurrently from consecutive children undergoing flexible bronchoscopy for chronic cough and cultured for bacterial pathogens. RESULTS: In cultures from 309 children (median age, 2.3 years) with chronic endobronchial suppuration, all main pathogens detected (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis) were more prevalent in nasopharyngeal than oropharyngeal swabs (37%, 34%, and 23% vs 21%, 6.2%, and 3.2%, respectively). Positive and negative predictive values for lower airway infection by any of these three pathogens were 63% (95% confidence interval [95% CI] 55, 70) and 85% (95% CI, 78, 91) for nasopharyngeal swabs, 65% (95% CI, 54, 75), and 66% (95% CI, 59, 72) for oropharyngeal swabs, and 61% (95% CI, 54,68), and 88% (95% CI, 81, 93) for both swabs, respectively. CONCLUSIONS: Neither nasopharyngeal nor oropharyngeal swabs, alone or in combination, reliably predicted lower airway infection in children with chronic wet cough. Although upper airway specimens may be useful for bacterial carriage studies and monitoring antimicrobial resistance, their clinical utility in pediatric chronic lung disorders of endobronchial suppuration is limited.

Australasian bronchiolitis guideline.

AIM: Bronchiolitis is the most common lower respiratory tract disorder in infants aged less than 12 months, and research has demonstrated that there is substantial variation in practice patterns despite treatment being well defined. In order to align and improve the consistency of the management of bronchiolitis, an evidence-based guideline was developed for the Australasian population. METHODS: The guideline development committee included representation from emergency and paediatric specialty medical and nursing personnel in addition to geographical representation across Australia and New Zealand - rural, remote and metropolitan. Formulation of the guideline included identification of population, intervention, comparator, outcomes and time questions and was associated with an extensive literature search from 2000 to 2015. Evidence was summarised and graded using the National Health and Medical Research Council and Grading of Recommendations Assessment, Development and Evaluation methodology, and consensus within the guideline group was sought using nominal group technique principles to formulate the clinical practice recommendations. The guideline was reviewed and endorsed by key paediatric health bodies. RESULTS: The guideline consists of a usable clinical interface for bedside functionality supported by evidence summary and tables. The Grading of Recommendations Assessment, Development and Evaluation and National Health and Medical Research Council processes provided a systematic and transparent process to review and assess the literature, resulting in a guideline that is relevant to the management of bronchiolitis in the Australasian setting. CONCLUSION: This is the first robust Australasian acute paediatric guideline and provides clear guidance for the management of the vast majority of patients seen in Australasian emergency departments and general paediatric wards with bronchiolitis.

Clinical presentation and medical management of melioidosis in children: a 24-year prospective study in the Northern Territory of Australia and review of the literature.

BACKGROUND: Melioidosis is less common in children than adults. The clinical spectrum of disease varies greatly between the 2 groups. Treatment guidelines are currently based on adult studies, and revision of existing guidelines is necessary to instruct specific pediatric management. METHODS: Culture-confirmed cases of melioidosis in the Northern Territory between 1989 and 2013 were identified from the Prospective Melioidosis Study. The epidemiology and clinical spectrum of disease for children aged ≤ 16 years were analyzed and compared with the adult data. RESULTS: Forty-five pediatric patients were identified, representing 5% of the total 820 melioidosis cases over 24 years. Most children (84%) had no recognized risk factors for melioidosis, and 80% presented during the wet season. Primary cutaneous melioidosis was the commonest presentation in children (60% vs 13%; P < .001), whereas pneumonia predominated in adults (54% vs 20%; P < .001). Bacteremia was less common in children than in adults (16% vs 59%; P < .001). Brainstem encephalitis occurred in 3 children without risk factors. Children were more likely to report an inoculating event (42%; P < .001). There was no difference in mortality between the groups (P = .178), with 3 children dying (7%); all had identifiable risk factors. Four children with cutaneous melioidosis were successfully treated with oral therapy alone, while 2 had skin lesions that resolved spontaneously. CONCLUSIONS: Pediatric melioidosis commonly manifests as localized cutaneous disease in immunocompetent hosts. The disease can be fatal, especially in individuals with risk factors for disease. Melioidosis with encephalomyelitis can result in severe residual disability. Prompt diagnosis requires a high index of clinical suspicion in endemic areas.

Bronchoscopy contributes to the clinical management of indigenous children newly diagnosed with bronchiectasis.

BACKGROUND: Some pediatric centers perform flexible bronchoscopy (FB) routinely when bronchiectasis is suspected. However, there are no published data evaluating this practice. OBJECTIVE: To evaluate the contribution of FB and bronchoalveolar lavage (BAL) to the initial management of children newly diagnosed with non-cystic fibrosis (CF) bronchiectasis. METHOD: We examined FB and BAL data collected prospectively in 56 children aged 0.8-9.8 years during initial investigations for bronchiectasis. Investigations contributed to management if any of the following were identified: (1) airway obstruction requiring additional intervention, (2) lower airway eosinophilia (BAL eosinophils >2.5%), or (3) BAL fluid culture >10(4) colony-forming units/ml of a respiratory bacterial pathogen requiring change from usual empiric antibiotics. RESULTS: Of the 56 children undergoing FB, there were 25 occasions in 23 children where these procedures altered empiric treatment. Lower airway eosinophilia was identified in 19 (34%) children, BAL microbiology results led to antibiotic changes in 5 (9%) and an unsuspected foreign body was found in another (2%). Strongyloides serology was performed in 38 children, including 12 of the 19 with airway eosinophilia, and was positive in 5 of these 12 children (42%). CONCLUSION: Contrary to some expert recommendations that FB should only be performed when bronchiectasis is localized, our data suggest that FB with BAL should at least be included in the initial investigations of Indigenous children with non-CF bronchiectasis.

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. FUNDING: National Health and Medical Research Council (Australia) and Health Research Council (New Zealand).

Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial.

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.

Rates of radiologically confirmed pneumonia as defined by the World Health Organization in Northern Territory Indigenous children.

OBJECTIVE: To determine the burden of hospitalised, radiologically confirmed pneumonia (World Health Organization protocol) in Northern Territory Indigenous children. DESIGN, SETTING AND PARTICIPANTS: Historical, observational study of all hospital admissions for any diagnosis of NT resident Indigenous children, aged between > or = 29 days and < 5 years, 1 April 1997 to 31 March 2005. INTERVENTION: All chest radiographs taken during these admissions, regardless of diagnosis, were assessed for pneumonia in accordance with the WHO protocol. MAIN OUTCOME MEASURE: The primary outcome was endpoint consolidation (dense fluffy consolidation [alveolar infiltrate] of a portion of a lobe or the entire lung) present on a chest radiograph within 3 days of hospitalisation. RESULTS: We analysed data on 24,115 hospitalised episodes of care for 9492 children and 13,683 chest radiographs. The average annual cumulative incidence of endpoint consolidation was 26.6 per 1000 population per year (95% CI, 25.3-27.9); 57.5 per 1000 per year in infants aged 1-11 months, 38.3 per 1000 per year in those aged 12-23 months, and 13.3 per 1000 per year in those aged 24-59 months. In all age groups, rates of endpoint consolidation in children in the arid southern region of NT were about twice that of children in the tropical northern region. CONCLUSION: The rates of severe pneumonia in hospitalised NT Indigenous children are among the highest reported in the world. Reducing this unacceptable burden of disease should be a national health priority.

The Royal Darwin Hospital as a centre of excellence for clinical training in Aboriginal health: still a dream.

Strong leadership is required to overcome the bureaucratic and financial obstacles.