Jessica E Pittman1, Kristine M Wylie1,2, Kathryn Akers1, Gregory A Storch1, Joseph Hatch3, Jane Quante1, Katherine B Frayman4,5,6, Nadeene Clarke4,5,6, Miriam Davis3, Stephen M Stick7,8,9, Graham L Hall8,10,11, Gregory Montgomery3, Sarath Ranganathan4,5,6, Stephanie D Davis3, Thomas W Ferkol1,12. 1. 1 Department of Pediatrics and. 2. 2 McDonnell Genome Institute, Washington University, St. Louis, Missouri. 3. 3 Department of Pediatrics, Section of Pediatric Pulmonology, Allergy and Sleep Medicine, Riley Children's Health, Indiana University School of Medicine, Indianapolis, Indiana. 4. 4 Department of Paediatrics, University of Melbourne, Melbourne, Australia. 5. 5 Respiratory Diseases Group, Murdoch Children's Research Institute, Melbourne, Australia. 6. 6 Department of Respiratory Medicine, Royal Children's Hospital, Melbourne, Australia. 7. 7 School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. 8. 8 Telethon Kids Institute, Perth, Australia. 9. 9 Princess Margaret Hospital for Children, Perth, Australia. 10. 10 School of Physiotherapy and Exercise Science, Curtin University, Perth, Australia. 11. 11 Centre of Child Health Research, University of Western Australia, Perth, Australia; and. 12. 12 Department of Cell Biology and Physiology, Washington University, St. Louis, Missouri.
Abstract
RATIONALE: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation. OBJECTIVES: To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF. METHODS: Infants with CF from U.S. and Australian centers were enrolled in a prospective, observational study examining the bacterial microbiota and inflammatory profiles of the respiratory tract. Bacterial diversity and density (load) were measured. Lavage samples were analyzed for inflammatory markers (interleukin 8, unbound neutrophil elastase, and absolute neutrophil count) in the epithelial lining fluid. RESULTS: Thirty-two infants (mean age, 4.7 months) underwent bronchoalveolar lavage and oropharyngeal sampling. Shannon diversity strongly correlated between upper and lower airway samples from a given subject, although community compositions differed. Microbial diversity was lower in younger subjects and in those receiving daily antistaphylococcal antibiotic prophylaxis. In lavage samples, reduced diversity correlated with lower interleukin 8 concentration and absolute neutrophil count. CONCLUSIONS: In infants with CF, reduced bacterial diversity in the upper and lower airways was strongly associated with the use of prophylactic antibiotics and younger age at the time of sampling; less diversity in the lower airway correlated with lower inflammation on bronchoalveolar lavage. Our findings suggest modification of the respiratory microbiome in infants with CF may influence airway inflammation.
RATIONALE: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation. OBJECTIVES: To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF. METHODS:Infants with CF from U.S. and Australian centers were enrolled in a prospective, observational study examining the bacterial microbiota and inflammatory profiles of the respiratory tract. Bacterial diversity and density (load) were measured. Lavage samples were analyzed for inflammatory markers (interleukin 8, unbound neutrophil elastase, and absolute neutrophil count) in the epithelial lining fluid. RESULTS: Thirty-two infants (mean age, 4.7 months) underwent bronchoalveolar lavage and oropharyngeal sampling. Shannon diversity strongly correlated between upper and lower airway samples from a given subject, although community compositions differed. Microbial diversity was lower in younger subjects and in those receiving daily antistaphylococcal antibiotic prophylaxis. In lavage samples, reduced diversity correlated with lower interleukin 8 concentration and absolute neutrophil count. CONCLUSIONS: In infants with CF, reduced bacterial diversity in the upper and lower airways was strongly associated with the use of prophylactic antibiotics and younger age at the time of sampling; less diversity in the lower airway correlated with lower inflammation on bronchoalveolar lavage. Our findings suggest modification of the respiratory microbiome in infants with CF may influence airway inflammation.
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