title: Pre-transplant impedance measures of reflux are associated with early allograft injury after lung transplantation.
abstract: BACKGROUND
  Acid reflux has been associated with poorer outcomes after lung transplantation. Standard pre-transplant reflux assessment has not been universally adopted. Non-acid reflux may also induce a pulmonary inflammatory cascade, leading to acute and chronic rejection. Esophageal multichannel intraluminal impedance and pH testing (MII-pH) may be valuable in standard pre-transplant evaluation. We assessed the association between pre-transplant MII-pH measures and early allograft injury in lung transplant patients.
  
  
  METHODS
  This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant MII-pH at a tertiary center from 2007 to 2012. Results from pre-transplant MII-pH, cardiopulmonary function testing, and results of biopsy specimen analysis of the transplanted lung were recorded. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods to assess the associations between MII-pH measures and development of acute rejection or lymphocytic bronchiolitis.
  
  
  RESULTS
  Thirty patients (46.7% men; age, 54.2 years) met the inclusion criteria. Pre-transplant cardiopulmonary function and pulmonary diagnoses were similar between outcome groups. Prolonged bolus clearance (hazard ratio [HR], 4.11; 95% confidence interval [CI], 1.34-12.57; p = 0.01), increased total distal reflux episodes (HR, 4.80; 95% CI, 1.33-17.25; p = 0.02), and increased total proximal reflux episodes (HR, 4.43; 95% CI, 1.14-17.31; p = 0.03) were significantly associated with decreased time to early allograft injury. Kaplan-Meier curves also demonstrated differences in time to rejection by prolonged bolus clearance (p = 0.01) and increased total distal reflux episodes (p = 0.01). Sub-group analysis including only patients with MII-pH performed off proton pump inhibitors (n = 24) showed similar results.
  
  
  CONCLUSIONS
  Prolonged bolus clearance, increased total distal reflux episodes, and increased total proximal reflux episodes on pre-transplant MII-pH were associated with decreased time to early allograft injury after lung transplantation. Routine pre-transplant MII-pH may provide clinically relevant data regarding transplant outcomes and peri-transplant care.
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts; Department of Gastroenterology, Boston VA Healthcare System, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Wai-Kit
authors.initials: WK
authors.lastname: Lo
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Burakoff
authors.affiliation: Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Goldberg
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Natan
authors.initials: N
authors.lastname: Feldman
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: wwchan@partners.org.
authors.forename: Walter W
authors.initials: WW
authors.lastname: Chan
mesh_terms: D000208:Acute Disease; D064591:Allografts; D017097:Electric Impedance; D050782:Esophageal pH Monitoring; D005260:Female; D005500:Follow-Up Studies; D005764:Gastroesophageal Reflux / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D006084:Graft Rejection / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015994:Incidence; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D011379:Prognosis; D012131:Respiratory Insufficiency / Q000150:complications / Q000601:surgery*; D012189:Retrospective Studies; D013997:Time Factors
keywords: acute rejection; early allograft injury; esophageal multichannel intraluminal impedance; gastroesophageal reflux disease; lung transplantation; lymphocytic bronchiolitis; pre-transplant evaluation