Risk Factors for Acute Rejection in the First Year after Lung Transplant: A Multicenter Study.
RATIONALE: Acute rejection, manifest 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: Evaluate clinical factors associated with biopsy proven acute rejection during the first posttransplant 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 first AR occurrence. MEASUREMENTS AND MAIN RESULTS: 53.3% of patients experienced at least one AR episode during the first posttransplant year. Multivariable proportional hazards analyses accounting for enrolling center effects identified four or greater HLA mismatches (HR 2.06, p=<0.01) as associated with increased AR hazards, while bilateral transplantation (HR 0.57, p=<0.01) was associated with protection from AR. Additionally, Wilcoxon rank-sum analyses demonstrated bilateral (vs. single) lung recipients and those with fewer than 4 (vs greater than 4) HLA mismatches demonstrated reduced AR frequency and/or severity during the first posttransplant year. CONCLUSIONS: We found a high incidence of AR in a contemporary multicenter lung transplant cohort undergoing consistent biopsy sampling. While not previously recognized, the finding of reduced AR in bilateral lung recipients is intriguing, warranting replication and mechanistic exploration.
Todd, JL; Neely, ML; Kopetskie, H; Sever, ML; Kirchner, J; Frankel, CW; Snyder, LD; Pavlisko, EN; Martinu, T; Tsuang, W; Shino, MY; Williams, N; Robien, MA; Singer, LG; Budev, M; Shah, PD; Reynolds, JM; Palmer, SM; Belperio, JA; Weigt, SS
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