Association of Chronic Proton Pump Inhibitor Use in Lung Transplant Recipients with Long-Term Outcomes: A Retrospective Cohort Study

Purpose Proton pump inhibitors (PPI) are widely prescribed long-term for lung transplant recipients in the absence of proven PPI-indicated conditions, despite little evidence supporting this practice. Several adverse effects related to chronic PPI use have been reported in observational studies in the general population. We aimed to assess whether chronic PPI use in lung transplant recipients is associated with benefits in long-term outcomes, specifically chronic lung allograft dysfunction (CLAD) and death/retransplant. Methods All adult lung transplant recipients transplanted between 1999 and 2018 who survived past 1-year post-transplant and had at least 4 pulmonary function tests were included. Patients were classified as on-PPI if there was a recorded prescription in the electronic medical record for dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole before 1-year post-transplant that continued after 1-year post-transplant. All other patients were classified as off-PPI. Cox proportional hazards models were used to determine the associations between PPI use and outcomes. Results 171 patients were off-PPI and 1394 patients were on-PPI. 780 patients developed CLAD and 808 died/were retransplanted. Compared to the on-PPI group, the off-PPI group was younger, had fewer re-transplants, and more transplants before 2010. In univariable analyses, PPI use was protective against CLAD (HR=0.76[0.62-0.94], p=0.01) and death/retransplant (HR=0.82[0.67-0.99], p=0.04). These associations were no longer significant after adjusting for age, sex, transplant type, transplant number, transplant era, primary disease, and CMV mismatch in multivariable analyses for CLAD (HR=0.87[0.70-1.08], p=0.20) and death/retransplant (HR=0.83[0.68-1.02], p=0.07). Conclusion In a retrospective cohort study, chronic PPI use after the first post-transplant year in lung transplant recipients was associated with a non-statistically significant benefit in death/retransplant, independent of potential confounders. As additional unknown confounders may exist, prospective randomized studies are needed to provide higher levels of evidence. Nevertheless, it may be reasonable to re-evaluate the practice of widely prescribing long-term PPIs in lung transplant recipients lacking a clear indication. Proton pump inhibitors (PPI) are widely prescribed long-term for lung transplant recipients in the absence of proven PPI-indicated conditions, despite little evidence supporting this practice. Several adverse effects related to chronic PPI use have been reported in observational studies in the general population. We aimed to assess whether chronic PPI use in lung transplant recipients is associated with benefits in long-term outcomes, specifically chronic lung allograft dysfunction (CLAD) and death/retransplant. All adult lung transplant recipients transplanted between 1999 and 2018 who survived past 1-year post-transplant and had at least 4 pulmonary function tests were included. Patients were classified as on-PPI if there was a recorded prescription in the electronic medical record for dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole before 1-year post-transplant that continued after 1-year post-transplant. All other patients were classified as off-PPI. Cox proportional hazards models were used to determine the associations between PPI use and outcomes. 171 patients were off-PPI and 1394 patients were on-PPI. 780 patients developed CLAD and 808 died/were retransplanted. Compared to the on-PPI group, the off-PPI group was younger, had fewer re-transplants, and more transplants before 2010. In univariable analyses, PPI use was protective against CLAD (HR=0.76[0.62-0.94], p=0.01) and death/retransplant (HR=0.82[0.67-0.99], p=0.04). These associations were no longer significant after adjusting for age, sex, transplant type, transplant number, transplant era, primary disease, and CMV mismatch in multivariable analyses for CLAD (HR=0.87[0.70-1.08], p=0.20) and death/retransplant (HR=0.83[0.68-1.02], p=0.07). In a retrospective cohort study, chronic PPI use after the first post-transplant year in lung transplant recipients was associated with a non-statistically significant benefit in death/retransplant, independent of potential confounders. As additional unknown confounders may exist, prospective randomized studies are needed to provide higher levels of evidence. Nevertheless, it may be reasonable to re-evaluate the practice of widely prescribing long-term PPIs in lung transplant recipients lacking a clear indication.