Long-Term Proton Pump Inhibitors in Lung Transplant Recipients: Near-Universal Use Without Clear Impact on Clinical Outcomes Over a 20-Year Observational Study.
Long-term proton pump inhibitor use became near-universal in lung transplant recipients without observable effect on clinical outcomes including CLAD, death, or retransplant over a 20-year observational period.
Key Findings
Results
PPI use was near-universal among lung transplant recipients and increased over time.
1170 of 1308 LTR (89.4%) were exposed to PPI, defined as ≥8 continuous weeks in the first year, started within 6 months post-transplant.
PPI use increased over the study period and remained above 90% from 2007 onwards.
The study cohort consisted of adult first-time lung transplant recipients between 1999 and 2018 who were alive and CLAD-free at 1-year post-transplant.
Single-center retrospective cohort design was used with n=1308 total LTR included.
Results
PPI exposure was not associated with differences in time to CLAD compared to no PPI use in multivariable analyses.
Multivariable analyses showed LTR on PPI had similar time to CLAD compared to those not on PPI.
CLAD (chronic lung allograft dysfunction) is described as the main barrier to long-term survival in lung transplant recipients.
The comparison was performed in patients who were alive and CLAD-free at 1 year post-transplant, removing early events from the analysis.
Results
PPI exposure was not associated with differences in time to death or retransplant in multivariable analyses.
Multivariable analyses showed LTR on PPI had similar time to death/retransplant compared to those not on PPI.
No observable effect on clinical outcomes was found despite near-universal PPI use over the 20-year observational period.
Results
No differences in clinical outcomes were observed between once-daily and twice-daily PPI dosing regimens.
Comparisons between LTR on once-daily and twice-daily dosing showed no differences in outcomes.
This subgroup analysis was performed within the PPI-exposed group to assess whether dose intensity affected results.
Results
Number of reflux episodes on 24-hour pH-impedance monitoring did not affect clinical outcomes after accounting for PPI use.
No differences in outcomes were observed after accounting for the number of reflux episodes on 24-hour pH-impedance monitoring.
This analysis suggests that objectively measured reflux burden did not modify the relationship between PPI use and clinical outcomes.
Results
Positive bronchoalveolar lavage cultures and acute rejection rates in the first year post-transplant were comparable between PPI-exposed and unexposed groups.
Positive bronchoalveolar lavage (BAL) cultures over the first year post-transplant were comparable between PPI and non-PPI groups.
Acute rejection rates over the first year post-transplant were also comparable between groups.
These findings suggest PPI use did not confer measurable microbiological or immunological differences in the early post-transplant period.
Background
GERD is a known risk factor for CLAD and PPI data in lung transplant recipients were sparse prior to this study.
The authors describe GERD as 'a known risk factor for chronic lung allograft dysfunction (CLAD), the main barrier to long-term survival in lung transplant recipients.'
Prior to this study, 'data are sparse on the prevalence of long-term PPI use and association with clinical outcomes' in LTR.
PPI are described as 'effective for symptomatic treatment of GERD.'
What This Means
This research suggests that proton pump inhibitors (PPIs) — common acid-reducing medications like omeprazole — became nearly standard practice in lung transplant patients over a 20-year period at one transplant center, with over 90% of patients receiving them from 2007 onward. The rationale for widespread use has been that acid reflux (GERD) is thought to harm transplanted lungs and contribute to a serious complication called chronic lung allograft dysfunction (CLAD), which is the leading cause of long-term transplant failure. PPIs are prescribed to reduce stomach acid and potentially protect the transplanted lung from reflux-related damage.
However, this study found that despite near-universal PPI use, patients who took PPIs did not have better outcomes than those who did not. There were no significant differences in rates of CLAD, death, or need for retransplantation between the two groups. Additionally, taking PPIs once daily versus twice daily made no difference, and even accounting for how much acid reflux patients actually had (measured objectively by 24-hour pH monitoring) did not change the findings. Rates of lung infections detected by bronchoalveolar lavage and acute rejection episodes were also similar between groups.
This research suggests that the routine prescription of PPIs to all lung transplant recipients may not provide the clinical benefit that has been assumed. The authors conclude that these findings 'question the routine use of PPI in LTR' and call for further research. This is notable because PPIs are not without potential long-term risks, and their widespread, possibly reflexive use in this population may warrant reconsideration through more rigorous prospective studies.
Zhang C, Ramendra R, Aversa M, Ghany R, Tikkanen J, Huszti E, et al.. (2026). Long-Term Proton Pump Inhibitors in Lung Transplant Recipients: Near-Universal Use Without Clear Impact on Clinical Outcomes Over a 20-Year Observational Study.. Clinical transplantation. https://doi.org/10.1111/ctr.70706