• Jamie L Todd, S Sam Weigt, Megan L Neely, Maria V Grau-Sepulveda, Kristen Mason, Michelle L Sever, Karen Kesler, Jerry Kirchner, Courtney W Frankel, Tereza Martinu, Michael Y Shino, Annette M Jackson, Elizabeth N Pavlisko, Nikki Williams, Mark A Robien, Lianne G Singer, Marie Budev, Wayne Tsuang, Pali D Shah, John M Reynolds, Laurie D Snyder, John A Belperio, and Scott M Palmer.
• Duke University School of Medicine, Durham, North Carolina, United States.
• Am. J. Respir. Crit. Care Med. 2024 Oct 29.

RationaleChronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain.ObjectivesDetermine the prognosis and clinical risks for probable CLAD in a prospective multicenter cohort.MethodsClinical Trials in Organ Transplantation-20 included 745 CLAD-eligible adult lung recipients at 5 centers and applied rigorous methods to prospectively adjudicate probable CLAD. The impact of probable CLAD on graft loss was determined using a Cox model that considered CLAD as a time-dependent covariate. Regularized Cox modeling with LASSO penalty was used to evaluate donor or recipient characteristics and the occurrence and timing of posttransplant events as probable CLAD risks. Similar analyses were performed for definite CLAD.Measurements And Main ResultsProbable CLAD occurred in 29.7% of patients at 3 years posttransplant and conferred a marked increase in risk for graft loss (unadjusted HR 4.38, p<0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and specifically late presence (>90 days posttransplant) of donor-specific alloantibodies, acute rejection, acute lung injury, or organizing pneumonia contributed the greatest independent information about probable CLAD risk. Definite CLAD risks were similar.ConclusionsProbable CLAD identifies patients at high risk for graft loss, supporting prospective identification of this condition for early initiation of CLAD-directed interventions. More effective strategies to prevent posttransplant cytomegalovirus, inhibit allospecific immunity, and reduce tissue injury are needed to reduce probable CLAD and improve lung recipient survival.

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