32 research outputs found

    Three clinically distinct chronic pediatric airway infections share a common core microbiota

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    Copyright © 2014 by the American Thoracic Society. Rationale: DNA-based microbiological studies are moving beyond studying healthy human microbiota to investigate diverse infectious diseases, including chronic respiratory infections, such as those in the airways of peoplewith cystic fibrosis (CF) and non-CF bronchiectasis. The species identified in the respiratory secretionmicrobiota fromsuch patients can be classified into those that are common and abundant among similar subjects (core) versus those that are infrequent and rare (satellite). This categorization provides a vital foundation for investigating disease pathogenesis and improving therapy. However, whether the core microbiota of people with different respiratory diseases, which are traditionally associated with specific culturable pathogens, are unique or shared with other chronic infections of the lower airways isnotwell studied. Little is also known about how these chronic infection microbiota change from childhood to adulthood. Objectives: We sought to compare the core microbiota in respiratory specimens from children and adults with different chronic lung infections. Methods: We used bacterial 16S rRNA gene pyrosequencing, phylogenetic analysis, and ecological statistical tools to compare the core microbiota in respiratory samples from three cohorts of symptomatic children with clinically distinct airway diseases (protracted bacterial bronchitis, bronchiectasis,CF), and from four healthy children.Wethen compared the core pediatric respiratory microbiota with those in samples from adults with bronchiectasis and CF. Measurements and Main Results: All three pediatric disease cohorts shared strikingly similar core respiratory microbiota that differed from adult CF and bronchiectasis microbiota. The most common species in pediatric disease cohort sampleswere also detected in those from healthy children. The adult CF and bronchiectasis microbiota also differed from each other, suggesting common early infection airwaymicrobiota that diverge by adulthood.The shared core pediatric microbiota included both traditional pathogens and many species not routinely identified by standard culture. Conclusions: Our results indicate that these clinically distinct chronic airway infections share common early core microbiota, which are likely shaped by natural aspiration and impaired clearance of the same airway microbes, but that disease-specific characteristics select for divergent microbiota by adulthood. Longitudinal and interventional studies will be required to define the relationships between microbiota, treatments, and disease progression

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

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    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; 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
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