Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation

Abstract

Rationale: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.

Objectives: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates.

Methods: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively.

Measurements and main results: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB.

Conclusions: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

Keywords: biomarker; body composition; disability; frailty; lung transplantation.

Figure 1.

Comparison of the overlap of frailty diagnosis assessed by the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). The rectangle represents the number of subjects with both SPPB and FFP assessments performed. Of the 25 frail subjects ascertained by SPPB, 20 were also frail by FFP (80%; 95% confidence interval, 64–96%). Of the 395 subjects in this study overall, 226 underwent both FFP and SPPB frailty assessments.

Figure 2.

Box plots of (A) IL-6, (B) tumor necrosis factor (TNF) receptor 1, (C) insulin like growth factor (IGF)-1, and (D) leptin levels by frailty status. Horizontal lines within the box plots represent the medians, and borders of box plots represent the interquartile ranges (IQRs). Whiskers represent the highest value within 1.5 IQR of the upper quartile and lowest value within 1.5 IQR of the lower quantile. Dots represent outlier values. FFP = Fried Frailty Phenotype; SPPB = Short Physical Performance Battery. For FFP, comparisons are made between 26 cases and 26 age-, sex-, and diagnosis-matched controls. For SPPB, comparisons are made between 12 cases and 12 age-, sex-, and diagnosis-matched controls.

Figure 3.

Time to delisting or death before lung transplant by (A) Short Physical Performance Battery (SPPB) binary score, (B) Fried Frailty Phenotype (FFP) binary score, (C) Short Physical Performance Battery ordinal score, and (D) Fried Frailty Phenotype ordinal score. Solid lines represent frail, dotted lines represent prefrail, and dashed lines represent not frail. For SPPB, lower scores denote increased frailty; for FFP, higher scores denote increased frailty.