Occurrence and Risk Factors for Acute Lung Injury (ALI) and Organizing Pneumonia (OP) after Lung Transplant

Abstract

Purpose ALI and OP are histologic patterns of lung damage associated with poor long-term outcomes after lung transplantation. Yet the incidence of ALI and OP and associated clinical factors remain poorly understood. Methods The cohort was drawn from CTOT-20 (NCT02631720), a multicenter prospective lung transplant cohort study. The first 200 enrolled, transplanted subjects with ≥ 1 lung biopsy in the first year after transplant were included. Descriptive statistics were used to summarize ALI or OP events in the 1007 biopsies performed over the first posttransplant year in this cohort. Univariate Cox regression models were used to evaluate the impact of recipient factors on the time to first ALI or OP event. Time independent covariates included age, sex, native disease, transplant type, use of induction immunosuppression, type of primary maintenance immunosuppression, HLA mismatch, and grade 3 primary graft dysfunction (PGD) within 72 hours. Time dependent covariates included a positive fungal, bacterial, mycobacterial, or respiratory viral organism on a respiratory specimen and development of a donor specific antibody. Results Forty-eight patients (24%) experienced at least one ALI event over the first posttransplant year (max 4 per patient). Similarly, 50 patients (25%) experienced at least one OP event (max 3 per patient). The median time to first ALI event was 44 (IQR 24,90) days while the time to first OP was somewhat longer at 92 (IQR 35,203) days. Both ALI and OP were identified slightly more often on for cause vs. surveillance biopsies. The majority of ALI and OP events were not concurrent with other histologic findings, such as acute rejection. Cox analyses identified PGD (HR 2.27, p=0.01) and cyclosporine-based maintenance therapy (HR 2.15, p=0.01) as risk factors for ALI. Analyses for the outcome of OP also implicated PGD (HR 1.97, p=0.03) and cyclosporine maintenance (HR 2.59, p Conclusion OP and ALI are common patterns of lung allograft injury. We identified clinical risk factors for ALI and OP that are potentially modifiable. Ongoing analyses will validate these risks over extended cohort follow up using multivariable approaches. As such, this work may identify strategies to mitigate ALI and OP and improve lung recipient outcomes.