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

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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.

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Authors and Affiliations

  1. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Wai-Kit Lo, Robert Burakoff & Walter W. Chan

  2. Department of Gastroenterology, Boston VA Healthcare System, Boston, MA, USA

    Wai-Kit Lo

  3. Harvard Medical School, Boston, MA, USA

    Wai-Kit Lo, Hilary J. Goldberg, Robert Burakoff & Walter W. Chan

  4. Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Hilary J. Goldberg & Steve Boukedes

Authors
  1. Wai-Kit Lo
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  2. Hilary J. Goldberg
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  3. Steve Boukedes
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  4. Robert Burakoff
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  5. Walter W. Chan
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Contributions

WWC and WKL initiated study concepts and design; WKL, HG, and SB contributed to acquisition of data; WWC, WKL, HG, and RB performed analysis and interpretation of data; WWC and WKL drafted the manuscript; WWC, WKL, HG, and RB contributed to critical revision of manuscript for important intellectual content; WWC and WKL performed statistical analyses; WWC and RB provided administrative support and overall study supervision.

Corresponding author

Correspondence to Walter W. Chan.

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All the authors declare that they have no conflict of interest.

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Lo, WK., Goldberg, H.J., Boukedes, S. et al. Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation. Dig Dis Sci 63, 403–410 (2018). https://doi.org/10.1007/s10620-017-4827-0

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  • DOI: https://doi.org/10.1007/s10620-017-4827-0

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