Skip to main content
Erschienen in: Digestive Diseases and Sciences 2/2018

01.11.2017 | Original Article

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation

verfasst von: Wai-Kit Lo, Hilary J. Goldberg, Steve Boukedes, Robert Burakoff, Walter W. Chan

Erschienen in: Digestive Diseases and Sciences | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Yusen RD, Edwards LB, Kucheryavya AY, et al. The registry of the international society for heart and lung transplantation: thirty-first adult lung and heart-lung transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant. 2014;33:1009–1024.CrossRefPubMed Yusen RD, Edwards LB, Kucheryavya AY, et al. The registry of the international society for heart and lung transplantation: thirty-first adult lung and heart-lung transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant. 2014;33:1009–1024.CrossRefPubMed
2.
Zurück zum Zitat Hadjiliadis D, Davis RD, Steele MP, et al. Gastroesophageal reflux disease in lung transplant recipients. Clin Transplant. 2003;17:363–368.CrossRefPubMed Hadjiliadis D, Davis RD, Steele MP, et al. Gastroesophageal reflux disease in lung transplant recipients. Clin Transplant. 2003;17:363–368.CrossRefPubMed
3.
Zurück zum Zitat Young LR, Hadjiliadis D, Davis RD, Palmer SM. Lung transplantation exacerbates gastroesophageal reflux disease. Chest. 2003;124:1689–1693.CrossRefPubMed Young LR, Hadjiliadis D, Davis RD, Palmer SM. Lung transplantation exacerbates gastroesophageal reflux disease. Chest. 2003;124:1689–1693.CrossRefPubMed
4.
Zurück zum Zitat Blondeau K, Mertens V, Vanaudenaerde BA, et al. Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J. 2008;31:707–713.CrossRefPubMed Blondeau K, Mertens V, Vanaudenaerde BA, et al. Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J. 2008;31:707–713.CrossRefPubMed
5.
Zurück zum Zitat Palmer SM, Miralles AP, Howell DN, Brazer SR, Tapson VF, Davis RD. Gastroesophageal reflux as a reversible cause of allograft dysfunction after lung transplantation. Chest. 2000;118:1214–1217.CrossRefPubMed Palmer SM, Miralles AP, Howell DN, Brazer SR, Tapson VF, Davis RD. Gastroesophageal reflux as a reversible cause of allograft dysfunction after lung transplantation. Chest. 2000;118:1214–1217.CrossRefPubMed
6.
Zurück zum Zitat Davis CS, Mendez BM, Flint DV, et al. Pepsin concentrations are elevated in the bronchioalveolar lavage fluid of patients with idiopathic pulmonary fibrosis after lung transplantation. J Surg Res. 2013;185:e101–e108.CrossRefPubMedPubMedCentral Davis CS, Mendez BM, Flint DV, et al. Pepsin concentrations are elevated in the bronchioalveolar lavage fluid of patients with idiopathic pulmonary fibrosis after lung transplantation. J Surg Res. 2013;185:e101–e108.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Hartwig MG, Appel JZ, Li B, et al. Chronic aspiration of gastric fluid accelerates pulmonary allograft dysfunction in a rat model of lung transplantation. J Thorac Cardiovasc Surg. 2006;131:209–217.CrossRefPubMed Hartwig MG, Appel JZ, Li B, et al. Chronic aspiration of gastric fluid accelerates pulmonary allograft dysfunction in a rat model of lung transplantation. J Thorac Cardiovasc Surg. 2006;131:209–217.CrossRefPubMed
8.
Zurück zum Zitat Fisichella PM, Davis CS, Lowery E, Ramirez L, Gamelli RL, Kovacs EJ. Aspiration, localized pulmonary inflammation, and predictors of early-onset bronchiolitis obliterans syndrome after lung transplantation. J Am Coll Surg. 2013;217:90–100.CrossRefPubMedPubMedCentral Fisichella PM, Davis CS, Lowery E, Ramirez L, Gamelli RL, Kovacs EJ. Aspiration, localized pulmonary inflammation, and predictors of early-onset bronchiolitis obliterans syndrome after lung transplantation. J Am Coll Surg. 2013;217:90–100.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Lo W-K, Burakoff R, Goldberg H, Feldman N, Chan WW. Pre-transplant impedance measures of reflux are associated with early allograft injury after lung transplantation. J Heart Lung Transpl. 2015;34:26–35.CrossRef Lo W-K, Burakoff R, Goldberg H, Feldman N, Chan WW. Pre-transplant impedance measures of reflux are associated with early allograft injury after lung transplantation. J Heart Lung Transpl. 2015;34:26–35.CrossRef
10.
11.
Zurück zum Zitat Glanville AR, Aboyoun CL, Havryk A, Plit M, Rainer S, Malouf MA. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation. Am J Respir Crit Care Med. 2008;177:1033–1040.CrossRefPubMed Glanville AR, Aboyoun CL, Havryk A, Plit M, Rainer S, Malouf MA. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation. Am J Respir Crit Care Med. 2008;177:1033–1040.CrossRefPubMed
12.
Zurück zum Zitat Cantu E, Appel JZ, Hartwig MG, et al. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg. 2004;78:1142–1151.CrossRefPubMed Cantu E, Appel JZ, Hartwig MG, et al. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg. 2004;78:1142–1151.CrossRefPubMed
13.
Zurück zum Zitat Lo W-K, Goldberg HJ, Wee J, Fisichella PM, Chan WW. Both pre-transplant and early post-transplant anti-reflux surgery prevent development of early allograft injury after lung transplantation. J Gastrointest Surg. 2016;20:111–118.CrossRefPubMed Lo W-K, Goldberg HJ, Wee J, Fisichella PM, Chan WW. Both pre-transplant and early post-transplant anti-reflux surgery prevent development of early allograft injury after lung transplantation. J Gastrointest Surg. 2016;20:111–118.CrossRefPubMed
14.
Zurück zum Zitat Hoppo T, Jarido V, Pannathur A, et al. Antireflux surgery preserves lung function in patients with gastroesophageal reflux disease and end-stage lung disease before and after lung transplantation. Arch Surg. 2011;146:1041–1047.CrossRefPubMed Hoppo T, Jarido V, Pannathur A, et al. Antireflux surgery preserves lung function in patients with gastroesophageal reflux disease and end-stage lung disease before and after lung transplantation. Arch Surg. 2011;146:1041–1047.CrossRefPubMed
15.
Zurück zum Zitat Davis RD, Lau CL, Eubanks S, et al. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg. 2003;125:533–542.CrossRefPubMed Davis RD, Lau CL, Eubanks S, et al. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg. 2003;125:533–542.CrossRefPubMed
16.
Zurück zum Zitat Fisichella PM, Davis CS, Lowery E, et al. Pulmonary immune changes early after laparoscopic antireflux surgery in lung transplant patients with gastroesophageal reflux disease. J Surg Res. 2012;177:e65–e73.CrossRefPubMedPubMedCentral Fisichella PM, Davis CS, Lowery E, et al. Pulmonary immune changes early after laparoscopic antireflux surgery in lung transplant patients with gastroesophageal reflux disease. J Surg Res. 2012;177:e65–e73.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Fisichella PM, Davis CS, Lundberg PW, et al. The protective role of laparoscopic antireflux surgery against aspiration of pepsin after lung transplantation. Surgery. 2011;150:598–606.CrossRefPubMedPubMedCentral Fisichella PM, Davis CS, Lundberg PW, et al. The protective role of laparoscopic antireflux surgery against aspiration of pepsin after lung transplantation. Surgery. 2011;150:598–606.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Wang W-H, Huang J-Q, Zheng G-F, et al. Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: a meta-analysis. World J Gastroenterol. 2005;11:4067–4077.CrossRefPubMedPubMedCentral Wang W-H, Huang J-Q, Zheng G-F, et al. Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: a meta-analysis. World J Gastroenterol. 2005;11:4067–4077.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Alhazzani W, Alenezi F, Jaeschke RZ, Moayyedi P, Cook DJ. Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2013;41:693–705.CrossRefPubMed Alhazzani W, Alenezi F, Jaeschke RZ, Moayyedi P, Cook DJ. Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2013;41:693–705.CrossRefPubMed
21.
Zurück zum Zitat van Pinxteren B, Sigterman KE, Bonis P, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2010;11:CD002095. van Pinxteren B, Sigterman KE, Bonis P, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2010;11:CD002095.
22.
Zurück zum Zitat Clark K, Lam LT, Gibson S, Currow D. The effect of ranitidine versus proton pump inhibitors on gastric secretions: a meta-analysis of randomised control trials. Anaesthesia. 2009;64:652–657.CrossRefPubMed Clark K, Lam LT, Gibson S, Currow D. The effect of ranitidine versus proton pump inhibitors on gastric secretions: a meta-analysis of randomised control trials. Anaesthesia. 2009;64:652–657.CrossRefPubMed
23.
Zurück zum Zitat Puig I, Calzado S, Suarez D, Sanchez-Delgado J, Lopez S, Calvet X. Meta-analysis: comparative efficacy of H2-receptor antagonists and proton pump inhibitors for reducing aspiration risk during anaesthesia depending on the administration route and schedule. Pharmacol Res. 2012;65:480–490.CrossRefPubMed Puig I, Calzado S, Suarez D, Sanchez-Delgado J, Lopez S, Calvet X. Meta-analysis: comparative efficacy of H2-receptor antagonists and proton pump inhibitors for reducing aspiration risk during anaesthesia depending on the administration route and schedule. Pharmacol Res. 2012;65:480–490.CrossRefPubMed
25.
Zurück zum Zitat Ghebremariam YT, Cooke JP, Gerhart W, et al. Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis. J Transl Med. 2015;1:249.CrossRef Ghebremariam YT, Cooke JP, Gerhart W, et al. Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis. J Transl Med. 2015;1:249.CrossRef
26.
Zurück zum Zitat Ghebre YT, Raghu G. Idiopathic Pulmonary fibrosis: novel concepts of proton pump inhibitors as antifibrotic drugs. Am J Respir Crit Care Med. 2016;193:1345–1352.CrossRefPubMedPubMedCentral Ghebre YT, Raghu G. Idiopathic Pulmonary fibrosis: novel concepts of proton pump inhibitors as antifibrotic drugs. Am J Respir Crit Care Med. 2016;193:1345–1352.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36:405–413.CrossRefPubMed Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36:405–413.CrossRefPubMed
28.
Zurück zum Zitat Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124:519–526.CrossRefPubMedPubMedCentral Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124:519–526.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Khalili H, Huang ES, Jacobson BC, Camargo CA Jr, Feskanich D, Chan AT. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. BMJ. 2012;344:e372.CrossRefPubMedPubMedCentral Khalili H, Huang ES, Jacobson BC, Camargo CA Jr, Feskanich D, Chan AT. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. BMJ. 2012;344:e372.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107:1001–1010.CrossRefPubMed Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107:1001–1010.CrossRefPubMed
31.
Zurück zum Zitat Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11:483–490.CrossRefPubMed Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11:483–490.CrossRefPubMed
32.
Zurück zum Zitat Gavini S, Finn RT, Lo WK, et al. Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non-fibrotic disease among pre-lung transplant patients. Neurogastroenterol Motil. 2015;27:1326–1332.CrossRefPubMed Gavini S, Finn RT, Lo WK, et al. Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non-fibrotic disease among pre-lung transplant patients. Neurogastroenterol Motil. 2015;27:1326–1332.CrossRefPubMed
Metadaten
Titel
Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation
verfasst von
Wai-Kit Lo
Hilary J. Goldberg
Steve Boukedes
Robert Burakoff
Walter W. Chan
Publikationsdatum
01.11.2017
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 2/2018
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4827-0

Weitere Artikel der Ausgabe 2/2018

Digestive Diseases and Sciences 2/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.