Wai-Kit Lo1,2,3, Hilary J Goldberg3,4, Steve Boukedes4, Robert Burakoff1,3, Walter W Chan5,6. 1. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. 2. Department of Gastroenterology, Boston VA Healthcare System, Boston, MA, USA. 3. Harvard Medical School, Boston, MA, USA. 4. Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA. 5. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. wwchan@bwh.harvard.edu. 6. Harvard Medical School, Boston, MA, USA. wwchan@bwh.harvard.edu.
Abstract
BACKGROUND: Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. AIMS: To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. RESULTS: A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. CONCLUSIONS: Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.
BACKGROUND: Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. AIMS: To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. RESULTS: A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. CONCLUSIONS: Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.
Authors: P Marco Fisichella; Christopher S Davis; Erin Lowery; Matthew Pittman; James Gagermeier; Robert B Love; Elizabeth J Kovacs Journal: J Surg Res Date: 2012-04-18 Impact factor: 2.192
Authors: P Marco Fisichella; Christopher S Davis; Erin Lowery; Luis Ramirez; Richard L Gamelli; Elizabeth J Kovacs Journal: J Am Coll Surg Date: 2013-04-28 Impact factor: 6.113
Authors: Denis Hadjiliadis; R Duane Davis; Mark P Steele; Robert H Messier; Christine L Lau; Steve S Eubanks; Scott M Palmer Journal: Clin Transplant Date: 2003-08 Impact factor: 2.863
Authors: Christopher S Davis; Bernardino M Mendez; Diana V Flint; Karen Pelletiere; Erin Lowery; Luis Ramirez; Robert B Love; Elizabeth J Kovacs; P Marco Fisichella Journal: J Surg Res Date: 2013-06-29 Impact factor: 2.192