title: Aspiration and allograft injury secondary to gastroesophageal reflux occur in the immediate post-lung transplantation period (prospective clinical trial).
abstract: OBJECTIVE
  To provide novel pilot data to quantify reflux, aspiration, and allograft injury immediately post-lung transplantation.
  
  
  BACKGROUND
  Asymptomatic reflux/aspiration, associated with allograft dysfunction, occurs in lung transplant recipients. Early fundoplication has been advocated. Indications for surgery include elevated biomarkers of aspiration (bile salts) in bronchoalveolar lavage fluid (BALF). Measurements have been mostly documented after the immediate posttransplant period. We report the first prospective study of reflux/aspiration immediately posttransplantation to date.
  
  
  METHODS
  Lung transplant recipients were recruited over 12 months. At 1 month posttransplantation, patients completed a Reflux Symptom Index questionnaire and underwent objective assessment for reflux (manometry and pH/impedance). Testing was performed on maintenance proton pump inhibitor. BALF was assessed for pepsin, bile salts, interleukin-8 and neutrophils.
  
  
  RESULTS
  Eighteen lung transplant recipients, median age of 46 years (range: 22-59 years), were recruited. Eight of 18 patients had abnormal esophageal peristalsis. Five of 17 patients were positive on Reflux Symptom Index questionnaire. Twelve of 17 patients had reflux. Three patients exclusively had weakly acid reflux. Median acid exposure was 4.8% (range: 1%-79.9%) and median esophageal volume exposure was 1.6% (range: 0.7-5.5). There was a median of 72 reflux events (range: 27-147) per 24 hours. A correlation existed between Reflux Symptom Index score and proximal reflux (r = 0.533, P = 0.006). Pepsin was detected in 11 of 15 BALF samples signifying aspiration (median: 18 ng/mL; range: 0-43). Bile salts were undetectable, using spectrophotometry and rarely detectable using dual mass spectrometry (2/15) (levels 0.2 and 1.2 μmol/L). Lavage interleukin-8 and neutrophil levels were elevated. A correlation existed between proximal reflux events and neutrophilia (r = 0.52, P = 0.03).
  
  
  CONCLUSIONS
  Lung transplant recipients should be routinely assessed for reflux/aspiration within the first month posttransplant. Reflux/aspiration can be present early postoperatively. Pepsin was detected suggesting aspiration. Bile salts were rarely detected. Proximal reflux events correlated with neutrophilia, linked to allograft dysfunction and mortality. These results support the need for early assessment of reflux/aspiration, which may inform fundoplication.
authors.affiliation: *Northern Oesophago-Gastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom †Department of Gastroenterology, Sint Antonius Hospital, Nieuwegein, The Netherlands ‡Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom §Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom ¶Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: S Michael
authors.initials: SM
authors.lastname: Griffin
authors.forename: Andrew G N
authors.initials: AG
authors.lastname: Robertson
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Bredenoord
authors.forename: Iain A
authors.initials: IA
authors.lastname: Brownlee
authors.forename: Rachel
authors.initials: R
authors.lastname: Stovold
authors.forename: Malcolm
authors.initials: M
authors.lastname: Brodlie
authors.forename: Ian
authors.initials: I
authors.lastname: Forrest
authors.forename: John H
authors.initials: JH
authors.lastname: Dark
authors.forename: Jeff P
authors.initials: JP
authors.lastname: Pearson
authors.forename: Chris
authors.initials: C
authors.lastname: Ward
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005764:Gastroesophageal Reflux / Q000453:epidemiology*; D006084:Graft Rejection / Q000453:epidemiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016040:Lung Transplantation; D008297:Male; D008365:Manometry; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications / Q000453:epidemiology*; D011446:Prospective Studies; D053120:Respiratory Aspiration / Q000453:epidemiology*; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers