Acute Rejection (AR) and Lymphocytic Bronchiolitis (LB) in a Multicenter Lung Transplant Cohort

Purpose Despite the importance of AR and LB in lung recipients, the incidence and associated clinical factors have not been prospectively studied in a contemporary cohort. We used a multicenter lung transplant cohort to describe the incidence of AR and LB over the first posttransplant year, examine concurrent histology at the time of an AR/LB event, and determine recipient factors associated with AR or LB. Methods The cohort was drawn from CTOT-20 (NCT02631720), an observational study collecting prospective clinical outcome data on lung recipients at 5 North American centers. The first 200 enrolled, transplanted subjects with ≥1 lung biopsy within the first posttransplant year were included. Recipients were managed according to center-specific clinical care practices. Descriptive statistics were used to summarize AR or LB events and concurrent histology. Univariate Cox modeling was used to evaluate the impact of select recipient factors on the time to first occurrence of AR or LB. Results 1007 biopsies were performed over the first posttransplant year in this cohort. 56% and 17% of patients experienced at least one AR or LB episode, respectively. Rates of minimal and mild AR and minimal LB were similar on for cause vs. surveillance biopsies. While a majority of LB events were concurrent with AR, AR events generally occurred in isolation or were concurrent with non-rejection histopathology. Univariate analyses suggested a protective effect of induction immunosuppression on the risk for AR. We also observed a significant decrease in the hazard of AR and LB in bilateral, as compared to single, lung recipients (Figure). Conclusion We observed a higher incidence of AR than that reported by the ISHLT registry. This may, in part, be attributed to the practice of surveillance biopsies in all CTOT-20 centers. While the impact of induction on AR risk is consistent with ISHLT data, the novel association between transplant type and AR/LB will be further validated over extended cohort follow up using multivariable approaches.