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Aspiration and Allograft Injury Secondary to Gastroesophageal Reflux Occur in the Immediate Post–Lung Transplantation Period (Prospective Clinical Trial)

Griffin, S. Michael MD, FRCS*; Robertson, Andrew G. N. PhD, MRCS*; Bredenoord, Albert J. PhD; Brownlee, Iain A. PhD; Stovold, Rachel PhD; Brodlie, Malcolm PhD§; Forrest, Ian PhD, FRCP§; Dark, John H. FRCS§,¶; Pearson, Jeff P. PhD; Ward, Chris PhD§

doi: 10.1097/SLA.0b013e3182a6589b
Original Articles From the ESA Proceedings

Objectives: 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.

Lung transplant recipients can be assessed for reflux/aspiration within the first month posttransplant. Gastroesophageal reflux disease can be present early postoperatively and proximal reflux events correlated with bronchoalveolar lavage fluid neutrophilia, which is linked to allograft dysfunction and mortality. These results support the need for early assessment, which may then inform fundoplication.

*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.

Reprints: S. Michael Griffin, MD, FRCS, Gastrointestinal Surgery, Northern Oesophago-Gastric Unit, Royal Victoria Infirmary, Queen Victoria Rd, Newcastle upon Tyne, NE1 4LP, United Kingdom. E-mail:

Disclosure: Supported by funds from European Society for Organ Transplantation (A.G.N.R.), British Lung Foundation (A.G.N.R.), Medical Research Council (P.C., C.W.), and Biotechnology and Biological Sciences Research Council Diet and Health Research Industry Club (I.A.B.). The authors declare no conflicts of interest.

© 2013 by Lippincott Williams & Wilkins.