The Association Between Frailty and Chronic Lung Allograft Dysfunction After Lung Transplantation

Abstract

Background. After lung transplantation, both frailty and chronic lung allograft dysfunction (CLAD) commonly develop, and when they do, are associated with poorer outcomes. Given their potential shared mechanisms, we sought to explore the temporal relationship between frailty and CLAD onset. Methods. In a single center, we prospectively measured frailty by the short physical performance battery (SPPB) repeatedly after transplant. Because of the nature of the relationship between frailty and CLAD is unknown, we tested the association between frailty, modeled as a time-dependent predictor, and CLAD development as well as CLAD development, modeled as a time-dependent predictor, and frailty development. To do so, we used Cox proportional cause-specific hazards and conditional logistic regression models adjusted for age, sex, race, diagnosis, cytomegalovirus serostatus, posttransplant body mass index, and acute cellular rejection episodes as time-dependent covariates. We tested SPPB frailty as a binary (≤9 points) and continuous predictor (12-point scale); as an outcome, we defined frailty as SPPB ≤9. Results. The 231 participants were a mean age of 55.7 y (SD 12.1). After adjusting for covariates, the development of frailty within 3 y after lung transplant was associated with cause-specific CLAD risk (adjusted cause-specific hazard ratio: 1.76; 95% confidence interval [CI], 1.05-2.92 when defining frailty as SPPB ≤9 and adjusted cause-specific hazard ratio: 1.10, 95% CI, 1.03-1.18 per 1-point worsening in SPPB). CLAD onset did not appear to be a risk factor for subsequent frailty (odds ratio, 4.0; 95% CI, 0.4-197.0). Conclusions. Studying the mechanisms underlying frailty and CLAD could provide new insights into the pathobiology of both and potential targets for intervention.

Association of frailty with postoperative outcomes following thoracic transplantation: A national analysis

“… 30 Neutrophil chemotactic activity is thought to be particularly impaired, leading to reduced defense against bacterial infections. 30 Likewise, a recent work by Singer and colleagues 31 demonstrated frailty, as measured by the short physical performance battery, to be associated with chronic lung allograft dysfunction after LT. Such inflammatory factors may render frail patients more susceptible to post-transplant infections, given their weakened immune response.…”

Advances in lung transplantation: 60 years on

“…The concept of frailty is recognized as an important factor that particularly impacts wait‐list survival, perioperative morbidity and also potentially mortality 13 . While a successful LTx can reverse the frailty phenotype in the short term, recent studies have linked frailty to long term morbidity in the form of fracture risk 14 and CLAD 15 . Given the importance of characterizing frailty‐related LTx outcomes, 16 a consensus Lung Transplant Frailty Scale has just been developed for future detailed frailty evaluation 17 …”

Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients

“…Frailty is linked to delisting and death in lung transplant candidates, and predicts worse quality of life and survival post transplantation ( 62 , 150 ). Intriguingly, incident frailty after lung transplantation is also associated with increased risk for CLAD, suggesting that frailty may be associated with systemic inflammation that can drive chronic rejection ( 151 ). A pro-inflammatory subtype of frailty has been identified, with increased levels of IL-6, CRP, PTX3, TNF-R1, and IL-1RA, mitochondrial stress, sarcopenia, malnutrition, and decreased exercise tolerance ( 152 ).…”