title: Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation.
abstract: BACKGROUND
  Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation.
  
  
  METHODS
  Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.
  
  
  RESULTS
  BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α.
  
  
  CONCLUSIONS
  Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research-University of Qld, Translational Research Institute, Woolloongabba, Qld, Australia.
authors.forename: Alice C-H
authors.initials: AC
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Mater Adult Hospital, South Brisbane, Qld, Australia.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Martin
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research-University of Qld, Translational Research Institute, Woolloongabba, Qld, Australia; Department of Anatomical Pathology, Mater Health Services, South Brisbane, Qld, Australia.
authors.forename: Rohan
authors.initials: R
authors.lastname: Lourie
authors.affiliation: Infection and Immunity Theme, South Australia Health and Medical Research Institute, North Terrace, Adelaide, Australia; School of Medicine, Flinders University, Bedford Park, Adelaide, Australia.
authors.forename: Geraint B
authors.initials: GB
authors.lastname: Rogers
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research-University of Qld, Translational Research Institute, Woolloongabba, Qld, Australia; Department of Respiratory Medicine, Mater Adult Hospital, South Brisbane, Qld, Australia.
authors.forename: Lucy D
authors.initials: LD
authors.lastname: Burr
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research-University of Qld, Translational Research Institute, Woolloongabba, Qld, Australia.
authors.forename: Sumaira Z
authors.initials: SZ
authors.lastname: Hasnain
authors.affiliation: Department of Respiratory Medicine, Mater Adult Hospital, South Brisbane, Qld, Australia.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Bowler
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research-University of Qld, Translational Research Institute, Woolloongabba, Qld, Australia; School of Biomedical Science, The University of Queensland, Qld, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McGuckin
authors.affiliation: Immunity, Infection and Inflammation Program, Mater Research-University of Qld, Translational Research Institute, Woolloongabba, Qld, Australia; Department of Respiratory Medicine, Mater Adult Hospital, South Brisbane, Qld, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Serisier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001987:Bronchiectasis / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000382:microbiology; D016022:Case-Control Studies; D005260:Female; D006193:Haemophilus influenzae / Q000302:isolation & purification; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D058504:Th17 Cells / Q000378:metabolism*
chemical_list: D007378:Interleukins
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