Katherine B Frayman1,2,3, David S Armstrong4,5, Rosemary Carzino1,2, Thomas W Ferkol6,7, Keith Grimwood8, Gregory A Storch6, Shu Mei Teo9, Kristine M Wylie6,10, Sarath C Ranganathan1,2,3. 1. Department of Respiratory and Sleep Medicine, Royal Children's Hospital, Parkville, Victoria, Australia. 2. Respiratory Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. 3. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia. 4. Department of Respiratory Medicine, Monash Children's Hospital, Clayton, Victoria, Australia. 5. Department of Paediatrics, Monash University, Clayton, Victoria, Australia. 6. Department of Pediatrics, Washington University, St Louis, Missouri, USA. 7. Department of Cell Biology and Physiology, Washington University, St Louis, Missouri, USA. 8. Menzies Health Institute Queensland, Griffith University and Gold Coast Health, Gold Coast, Queensland, Australia. 9. Centre for System Genomics, University of Melbourne, Melbourne, Victoria, Australia. 10. McDonnell Genome Institute, Washington University, St Louis, Missouri, USA.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Jessica E Pittman; Kristine M Wylie; Kathryn Akers; Gregory A Storch; Joseph Hatch; Jane Quante; Katherine B Frayman; Nadeene Clarke; Miriam Davis; Stephen M Stick; Graham L Hall; Gregory Montgomery; Sarath Ranganathan; Stephanie D Davis; Thomas W Ferkol Journal: Ann Am Thorac Soc Date: 2017-10
Authors: Marianne S Muhlebach; Joseph E Hatch; Gisli G Einarsson; Stef J McGrath; Deirdre F Gilipin; Gillian Lavelle; Bojana Mirkovic; Michelle A Murray; Paul McNally; Nathan Gotman; Sonia Davis Thomas; Matthew C Wolfgang; Peter H Gilligan; Noel G McElvaney; J Stuart Elborn; Richard C Boucher; Michael M Tunney Journal: Eur Respir J Date: 2018-07-11 Impact factor: 16.671
Authors: Katherine B Frayman; Kristine M Wylie; David S Armstrong; Rosemary Carzino; Stephanie D Davis; Thomas W Ferkol; Keith Grimwood; Gregory A Storch; Sarath C Ranganathan Journal: J Cyst Fibros Date: 2018-12-21 Impact factor: 5.482
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