Frailty is Associated with Subsequent Development of Chronic Lung Allograft Dysfunction Following Lung Transplantation

Purpose Chronic lung allograft dysfunction (CLAD) is a commonly recognized cause of death after lung transplantation. Frailty is a state of low physiologic reserve that frequently develops after lung transplantation, independent of allograft function. It is associated with increased risks of post-transplant readmission and mortality. Systemic inflammation is thought to be a potential cause of frailty and may contribute to development of CLAD. In this analysis, we hypothesized that the development of frailty after transplant may be associated with later development of CLAD. Methods In 259 lung transplant recipients, we measured frailty using the Short Physical Performance Battery (SPPB) at 3, 6, 12, 18, 24, 30, and 36 months after lung transplantation. Frailty was evaluated as a binary (SPPB ≤ 9) and continuous (1-point incremental worsening in SPPB) predictor (minimal clinically important difference = 1 point). The date of CLAD Grade 1 development was abstracted from our research database. Cox proportional hazards models were used to test the association between post-transplant frailty as a time-varying predictor and development of CLAD. Analyses were adjusted for pre-operative age, sex, race, diagnosis, and body mass index (BMI) measured at each visit. Results In post-transplant follow-up, 115 patients (44%) were frail (SPPB ≤ 9); 129 patients (49%) ever demonstrated at least a 1-point worsening in SPPB. In unadjusted and adjusted analyses, frailty was associated with an increased risk of later developing CLAD. Frailty (SPPB ≤ 9) was associated with a 1.65-fold adjusted increased risk of CLAD. Further, one-point worsening in SPPB score was associated with a 1.08-fold increased risk of CLAD (Table). Conclusion Frailty is associated with increased subsequent risk of developing chronic lung allograft dysfunction following lung transplantation. Future studies should investigate mechanistic links between development of frailty post-transplant and subsequent risk of CLAD.