title: Bile acids in sputum and increased airway inflammation in patients with cystic fibrosis.
abstract: BACKGROUND
  Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux and aspiration of duodenogastric contents into the lungs. We aimed to assess aspiration in patients with CF by measuring duodenogastric components in induced sputum and to investigate whether the presence of bile acids (BAs) in sputum was correlated with disease severity and markers of inflammation.
  
  
  METHODS
  In 41 patients with CF, 15 healthy volunteers, 29 patients with asthma, and 28 patients with chronic cough, sputum was obtained after inhalation of hypertonic saline. Sputum supernatant was tested for BA and neutrophil elastase. Spirometry and BMI were assessed on the day of sputum collection.
  
  
  RESULTS
  Two of 15 healthy patients (13%), eight of 29 patients (28%) with asthma, four of 28 patients (14%) with chronic cough, and 23 of 41 patients (56%) with CF had BA in sputum. BA concentrations were similar in patients who are positive for BA with genotype F508del homozygote, F508del heterozygote, and other CF mutations and were not related with BMI and age. Patients with CF with BA in sputum had a higher concentration of neutrophil elastase compared with patients without BA in sputum (31.25 [20.33-54.78] μg/mL vs 14.45 [7.11-27.88] μg/mL, P < .05). There was a significant correlation between BA concentrations and dynamic lung volumes (FEV(1) % predicted [r = -0.53, P < .01], FVC% [r = -0.59, P < .01]) as well as with number of days of antibiotic IV treatment (r = 0.58, P < .01).
  
  
  CONCLUSIONS
  BAs are present in the sputum of more than one-half of patients with CF, suggesting aspiration of duodenogastric contents. Aspiration of BA was associated with increased airway inflammation. In patients with BA aspiration, the levels of BA were clearly associated with the degree of lung function impairment as well as the need for IV antibiotic treatment.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Ans
authors.initials: A
authors.lastname: Pauwels
authors.affiliation: Laboratory of Pneumology, University of Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Decraene
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Blondeau
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Mertens
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Ricard
authors.initials: R
authors.lastname: Farre
authors.affiliation: Department of Pediatrics, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Proesmans
authors.affiliation: Adult CF Center, Department of Respiratory Medicine, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: Van Bleyenbergh
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium; Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, England.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sifrim
authors.affiliation: Laboratory of Pneumology, University of Leuven, Leuven, Belgium; Adult CF Center, Department of Respiratory Medicine, University Hospital Gasthuisberg, Leuven, Belgium. Electronic address: lieven.dupont@uzleuven.be.
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism; D001647:Bile Acids and Salts / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002452:Cell Count; D003371:Cough / Q000378:metabolism; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005764:Gastroesophageal Reflux; D006801:Humans; D008297:Male; D008875:Middle Aged; D053120:Respiratory Aspiration / Q000209:etiology; D012129:Respiratory Function Tests; D012307:Risk Factors; D013183:Sputum / Q000737:chemistry* / Q000166:cytology; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers