Frailty after lung transplantation is associated with impaired health-related quality of life and mortality

Abstract

Background: Lung transplantation and related medications are associated with pathobiological changes that can induce frailty, a state of decreased physiological reserve. Causes of persistent or emergent frailty after lung transplantation, and whether such transplant-related frailty is associated with key outcomes, are unknown.

Methods: Frailty and health-related quality of life (HRQL) were prospectively measured repeatedly for up to 3 years after lung transplantation. Frailty, quantified by the Short Physical Performance Battery (SPPB), was tested as a time-dependent binary and continuous predictor. The association of transplant-related frailty with HRQL and mortality was evaluated using mixed effects and Cox regression models, respectively, adjusting for age, sex, ethnicity, diagnosis, and for body mass index and lung function as time-dependent covariates. We tested the association between measures of body composition, malnutrition, renal dysfunction and immunosuppressants on the development of frailty using mixed effects models with time-dependent predictors and lagged frailty outcomes.

Results: Among 259 adults (56% male; mean age 55.9±12.3 years), transplant-related frailty was associated with lower HRQL. Frailty was also associated with a 2.5-fold higher mortality risk (HR 2.51; 95% CI 1.21 to 5.23). Further, each 1-point worsening in SPPB was associated, on average, with a 13% higher mortality risk (HR 1.13; 95% CI 1.04 to 1.23). Secondarily, we found that sarcopenia, underweight and obesity, malnutrition, and renal dysfunction were associated with the development of frailty after transplant.

Conclusions: Transplant-related frailty is associated with lower HRQL and higher mortality in lung recipients. Abnormal body composition, malnutrition and renal dysfunction may contribute to the development of frailty after transplant. Confirming the role of these potential contributors and developing interventions to mitigate frailty may improve lung transplant success.

Keywords: lung transplantation.

Figure 1.. Conceptual model of the relationship of frailty with key outcomes.

The pathological changes caused by both advanced lung disease and lung transplantation lead to functional limitations, which are impairments in physical or mental performance that are quantifiable in a laboratory-based setting (i.e., measures of frailty or lung function). Functional limitations, in turn, can result in disability, reduced health-related quality of life (HRQL), and death. Pathological changes that could induce frailty after transplant include changes in body composition with development of sarcopenia and increased adiposity, nutritional deficiency, and renal dysfunction. These changes can be caused or exacerbated by chronic immunosuppression, in particular calcineurin inhibitors and steroids.

Figure 2.. Box plots of health-related quality of life (HRQL) by the presence of frailty after lung transplant.

Frailty was assessed with the Short Physical Performance Battery, which ranges from 0 to 12. Recipients with SPPB ≤ 7 were categorized as frail (white boxes), and those with SPPB >7 were categorized as not frail (gray boxes). HRQL was assessed by the SF12-Physical Component Score (generic-physical), the SF12-Mental Component Score (generic-mental), the Airway Questionnaire 20-Revised (respiratory specific), and the EuroQOL-5D (health utility).

Figure 3.. Survival after lung transplant by frailty change.

Kaplan Meier plots stratified by three different groups of changes in frailty measured by the Short Physical Performance Battery (SPPB) from 6- to 36-months or the participant’s last study visit. We defined the three groups as “unchanged” (participants who had no change in SPPB frailty); “improved” (SPPB score improved by ≥1 point); and “worsened” (SPPB score worsened by ≥1 point).