Risk Factors for Acute Rejection in the First Year after Lung Transplant. A Multicenter Study

Jamie L. Todd, Megan L. Neely, Heather Kopetskie, Michelle L. Sever, Jerry Kirchner, Courtney W. Frankel, Laurie D. Snyder, Elizabeth N. Pavlisko, Tereza Martinu, Wayne Tsuang, Michael Y. Shino, Nikki Williams, Mark A. Robien, Lianne G. Singer, Marie Budev, Pali D. Shah, John M. Reynolds, Scott M. Palmer, John A. Belperio, S. Sam Weigt

Research output: Contribution to journalArticle

Abstract

Rationale: Acute rejection, manifesting as lymphocytic inflammation in a perivascular (acute perivascular rejection [AR]) or peribronchiolar (lymphocytic bronchiolitis [LB]) distribution, is common in lung transplant recipients and increases the risk for chronic graft dysfunction.Objectives: To evaluate clinical factors associated with biopsy-proven acute rejection during the first post-transplant year in a present-day, five-center lung transplant cohort.Methods: We analyzed prospective diagnoses of AR and LB from over 2,000 lung biopsies in 400 newly transplanted adult lung recipients. Because LB without simultaneous AR was rare, our analyses focused on risk factors for AR. Multivariable Cox proportional hazards models were used to assess donor and recipient factors associated with the time to the first AR occurrence.Measurements and Main Results: During the first post-transplant year, 53.3% of patients experienced at least one AR episode. Multivariable proportional hazards analyses accounting for enrolling center effects identified four or more HLA mismatches (hazard ratio [HR], 2.06; P ≤ 0.01) as associated with increased AR hazards, whereas bilateral transplantation (HR, 0.57; P ≤ 0.01) was associated with protection from AR. In addition, Wilcoxon rank-sum analyses demonstrated bilateral (vs. single) lung recipients, and those with fewer than four (vs. more than four) HLA mismatches demonstrated reduced AR frequency and/or severity during the first post-transplant year.Conclusions: We found a high incidence of AR in a contemporary multicenter lung transplant cohort undergoing consistent biopsy sampling. Although not previously recognized, the finding of reduced AR in bilateral lung recipients is intriguing, warranting replication and mechanistic exploration.

Original languageEnglish (US)
Pages (from-to)576-585
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume202
Issue number4
DOIs
StatePublished - Aug 15 2020

Keywords

  • acute rejection
  • lung transplantation
  • lymphocytic bronchiolitis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Todd, J. L., Neely, M. L., Kopetskie, H., Sever, M. L., Kirchner, J., Frankel, C. W., Snyder, L. D., Pavlisko, E. N., Martinu, T., Tsuang, W., Shino, M. Y., Williams, N., Robien, M. A., Singer, L. G., Budev, M., Shah, P. D., Reynolds, J. M., Palmer, S. M., Belperio, J. A., & Weigt, S. S. (2020). Risk Factors for Acute Rejection in the First Year after Lung Transplant. A Multicenter Study. American journal of respiratory and critical care medicine, 202(4), 576-585. https://doi.org/10.1164/rccm.201910-1915OC