title: High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations.
abstract: BACKGROUND
  Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated.
  
  
  METHODS
  This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes.
  
  
  RESULTS
  The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status.
  
  
  CONCLUSIONS
  Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.
authors.affiliation: Respiratory Research Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. paul.mcnally@olchc.ie
authors.forename: P
authors.initials: P
authors.lastname: McNally
authors.forename: E
authors.initials: E
authors.lastname: Ervine
authors.forename: M D
authors.initials: MD
authors.lastname: Shields
authors.forename: B D
authors.initials: BD
authors.lastname: Dimitrov
authors.forename: B
authors.initials: B
authors.lastname: El Nazir
authors.forename: C C
authors.initials: CC
authors.lastname: Taggart
authors.forename: C M
authors.initials: CM
authors.lastname: Greene
authors.forename: N G
authors.initials: NG
authors.lastname: McElvaney
authors.forename: P
authors.initials: P
authors.lastname: Greally
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000032:analysis*; D008297:Male; D010434:Pepsin A / Q000032:analysis*; D053120:Respiratory Aspiration / Q000175:diagnosis / Q000209:etiology
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D010434:Pepsin A