title: FUT2genotype influences lung function, exacerbation frequency and airway microbiota in non-CF bronchiectasis.
abstract: OBJECTIVE
  To assess whetherFUT2(secretor) genotype affects disease severity and airway infection in patients with non-cystic fibrosis bronchiectasis.
  
  
  METHODS
  Induced sputum samples were obtained from 112 adult patients with high-resolution CT scan-proven bronchiectasis and at least two exacerbations in the previous year, as part of an unrelated randomised control trial.
  
  
  METHODS
  Presence of nullFUT2polymorphisms were determined by gene sequencing and verified by endobronchial biopsy histochemical staining. Outcome measures were FEV1% predicted, exacerbation frequency, and bacterial, fungal and viral components of the microbiota (measured by culture independent approaches).
  
  
  RESULTS
  Patients were grouped byFUT2loss-of-function genotype; categorised as non-secretors (n=27,sese), heterozygous secretors (n=54,Sese) or homozygous secretors (n=31,SeSe). FEV1% was significantly lower inSeSepatients compared withsesepatients (mean 61.6 (SD 20.0) vs 74.5 (18.0); p=0.023). Exacerbation frequency was significantly higher inSeSe(mean count 5.77) compared withsese(4.07; p=0.004) andSese(4.63; p=0.026) genotypes. The time until first exacerbation was significantly shorter inSeSecompared withSese(HR=0.571 (95% CI 0.343 to 0.950); p=0.031), with a similar trend forsesepatients (HR=0.577 (0.311 to 1.07); p=0.081).sesehad a significantly reduced frequency ofPseudomonas aeruginosa-dominated airway infection (8.7%) compared withSese(31%; p=0.042) andSeSe(36%; p=0.035). In contrast, fungal, viral and non-dominant bacterial components of the microbiome were not significantly different betweenFUT2genotypes.
  
  
  CONCLUSIONS
  FUT2genotype in patients with non-cystic fibrosis bronchiectasis was significantly associated with disease outcomes, with homozygous secretors exhibiting lower lung function, higher exacerbation number and a higher frequency ofP. aeruginosa-dominated infection.
  
  
  BACKGROUND
  ACTRN12609000578202 (anzctr.org.au); Pre-results.
authors: South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.|SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors: Steven L
authors: http://orcid.org/0000-0003-4357-8243
authors: SL
authors: Taylor
authors: Flinders Centre for Epidemiology and Biostatistics, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors: Richard J
authors: RJ
authors: Woodman
authors: School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors: Alice Ch
authors: AC
authors: Chen
authors: Immunity, Infection, and Inflammation Program, Mater Research Institute, University of Queensland and Translational Research Institute, Woolloongabba, Queensland, Australia.|Mater Health Services, South Brisbane, Queensland, Australia.
authors: Lucy D
authors: LD
authors: Burr
authors: Department of Microbiology and Infectious Diseases, Flinders University, Adelaide, South Australia, Australia.|SA Pathology, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors: David L
authors: DL
authors: Gordon
authors: Immunity, Infection, and Inflammation Program, Mater Research Institute, University of Queensland and Translational Research Institute, Woolloongabba, Queensland, Australia.
authors: Michael A
authors: MA
authors: McGuckin
authors: South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.|SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors: Steve
authors: S
authors: Wesselingh
authors: South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.|SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
authors: Geraint B
authors: GB
authors: Rogers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001987:Bronchiectasis / Q000235:genetics* / Q000382:microbiology* / Q000503:physiopathology*; D001999:Bronchoscopy; D018450:Disease Progression; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013183:Sputum / Q000382:microbiology; D014057:Tomography, X-Ray Computed; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase
keywords: Bacterial Infection; Bronchiectasis; Viral infection