A nonlinear relationship between visceral adipose tissue and frailty in adult lung transplant candidates

Abstract

Frailty is a state of decreased physiologic reserve associated with poor outcomes before and after lung transplantation. Obesity, particularly central obesity characterized by excess proinflammatory visceral adipose tissue (VAT), is associated with incident frailty in middle-aged and older adults. The association between VAT and frailty in advanced lung disease, however, is unknown. In two, nonoverlapping multicenter cohorts of adults listed for lung transplantation, we measured VAT area on bioelectrical impedance assay (BIA) in one cohort and cross-sectional VAT and subcutaneous adipose tissue (SAT) areas on abdominal computed tomography (CT) in the other. We identified a nonlinear relationship between greater VAT by BIA and frailty. In fully adjusted piecewise regression models, every 20 cm 2 increase in VAT area was associated with 50% increased odds of frailty in subjects with high VAT (95% CI 1.2-1.9, P < .001), and 10% decreased odds of frailty (95% CI 0.7-1.04, P = .12) in subjects with low VAT. Compared to frail subjects with low VAT, those with high VAT were more likely to have low grip strength and less likely to have weight loss, suggesting that mechanisms of frailty may differ by VAT. Further investigation of mechanisms linking VAT and frailty may identify new targets for prevention and treatment. K E Y W O R D Sclinical research/practice, lung transplantation/pulmonology, obesity, quality of life (QOL)

Clinical outcomes associated with computed tomography‐based body composition measures in lung transplantation: a systematic review

“…[21] observed that increased SAT from a single thoracic axial slice was associated with improved post‐transplant three‐year survival, whereas Gonzalez et al observed a lower three‐year survival with increased mediastinal fat volume, and no association was seen in the other two studies evaluating SAT and VAT [22,56]. In two of the studies, increased SAT on abdominal CT and increased mediastinal fat volumes were associated with a higher risk of developing PGD [33,56]. This supports the notion that abdominal SAT and mediastinal adipose tissue is associated with an increased inflammatory milieu [57] characterized by increased reactive oxygen species and decreased clearance of circulating fatty acids, both risk factors for accumulation of ectopic adiposity and PGD [58,59].…”

“…The analysis of CT morphometrics beyond muscle mass measurements is gaining increased recognition, as obesity has been shown to be associated with increased levels of inflammation, adipokines, and cellular senescence [54–56]. In the present review, four studies evaluated the association of adiposity tissue with post‐transplant survival with heterogeneous results.…”

“…Pienta et al . [21] observed that increased SAT from a single thoracic axial slice was associated with improved post‐transplant three‐year survival, whereas Gonzalez et al observed a lower three‐year survival with increased mediastinal fat volume, and no association was seen in the other two studies evaluating SAT and VAT [22,56]. In two of the studies, increased SAT on abdominal CT and increased mediastinal fat volumes were associated with a higher risk of developing PGD [33,56].…”

“…This supports the notion that abdominal SAT and mediastinal adipose tissue is associated with an increased inflammatory milieu [57] characterized by increased reactive oxygen species and decreased clearance of circulating fatty acids, both risk factors for accumulation of ectopic adiposity and PGD [58,59]. However, our understanding of the adipose tissue stores is evolving as abdominal VAT has been conceptualized as the more metabolically active tissue previously associated with increased cardio‐metabolic risk factors [60,61], increased frailty in LTx candidates [56], and increased limb muscle adiposity [62,63]. This accumulation of adiposity in the limb muscles may result in diminished protein synthesis, regenerative capacity, and decreased function [64–66].…”

“…Despite the heterogeneity across the included studies, this was the first comprehensive review and descriptive synthesis of CT body composition measures in LTx patients performed in accordance with the PRISMA guidelines [24]. Secondly, the studies included were all retrospective, single‐center studies with CT performed for clinical purposes, with the exception of one prospective multi‐centered study [56]. Thirdly, it is difficult to extrapolate some of these techniques across all pretransplant diagnoses as transplant indications such as cystic fibrosis or pulmonary hypertension were underrepresented across studies.…”