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The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis
  1. Katherine B Frayman1,2,3,
  2. David S Armstrong4,5,
  3. Rosemary Carzino1,2,
  4. Thomas W Ferkol6,7,
  5. Keith Grimwood8,
  6. Gregory A Storch6,
  7. Shu Mei Teo9,
  8. Kristine M Wylie6,10,
  9. Sarath C Ranganathan1,2,3
  1. 1Department of Respiratory and Sleep Medicine, Royal Children's Hospital, Parkville, Victoria, Australia
  2. 2Respiratory Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  3. 3Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  4. 4Department of Respiratory Medicine, Monash Children's Hospital, Clayton, Victoria, Australia
  5. 5Department of Paediatrics, Monash University, Clayton, Victoria, Australia
  6. 6Department of Pediatrics, Washington University, St Louis, Missouri, USA
  7. 7Department of Cell Biology and Physiology, Washington University, St Louis, Missouri, USA
  8. 8Menzies Health Institute Queensland, Griffith University and Gold Coast Health, Gold Coast, Queensland, Australia
  9. 9Centre for System Genomics, University of Melbourne, Melbourne, Victoria, Australia
  10. 10McDonnell Genome Institute, Washington University, St Louis, Missouri, USA
  1. Correspondence to Dr Katherine B Frayman, Department of Respiratory and Sleep Medicine, Royal Children's Hospital, 50 Flemington Road, Parkville, VIC 3052, Australia; katherine.frayman{at}rch.org.au

Abstract

Rationale In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain.

Objectives To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years.

Methods Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records.

Measurements and main results Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2–78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years.

Conclusions In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age.

  • Cystic Fibrosis
  • Bacterial Infection
  • Bronchoscopy
  • Paediatric Lung Disaese

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Footnotes

  • Contributors KBF performed the literature search, was involved in data collection and analysis, wrote the first draft of the manuscript and was involved in preparing the figures. DSA, RC and KG were authors of the previous studies of this birth cohort and were responsible for the initial study design, recruitment, data collection and analysis. SCR was responsible for the design of this study. TWF, GAS and KMW performed the 16S rRNA gene sequencing of the BAL samples. SMT analysed the 16S rRNA gene data and prepared the figures. KBF, DSA, KG, TWF, GAS, KMW, SMT and SCR were all involved in data interpretation. All authors contributed to the editing of subsequent manuscript drafts.

  • Funding 16S rRNA gene sequencing was funded by grants from the MCRI ‘65 km for CF’ and the RCH CF Research Trust (CFRT). KBF was supported by the Thoracic Society of Australia and New Zealand/Vertex CF Paediatric Clinical Fellowship, the RCH CFRT, the Australian CFRT Postgraduate Studentship and an Australian Government Research Training Program Scholarship. TWF, SCR GAS and KMW were supported by the National Institutes of Health (NIH) grant, HL116211 and National Health and Medical Research Council award, NHMRC1043768.

  • Competing interests None declared.

  • Ethics approval Royal Children's Hospital, Melbourne, Human Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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