title: Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation.
abstract: BACKGROUND
  Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Department of Medicine and.
authors.forename: Jonathan P
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authors.lastname: Singer
authors.affiliation: 2 Department of Medicine and.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Diamond
authors.affiliation: 3 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Cynthia J
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authors.lastname: Gries
authors.affiliation: 4 Department of Medicine.
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authors.lastname: Shah
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authors.forename: Monica Y
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authors.lastname: Dean
authors.affiliation: 3 Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
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authors.lastname: Tokman
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authors.lastname: Arcasoy
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authors.lastname: Ramphal
authors.affiliation: 1 Department of Medicine and.
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authors.lastname: Greenland
authors.affiliation: 5 Department of Surgery, College of Physicians and Surgeons, and.
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authors.affiliation: 5 Department of Surgery, College of Physicians and Surgeons, and.
authors.forename: Pricilla
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authors.lastname: Heffernan
authors.affiliation: 4 Department of Medicine.
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authors.lastname: Shah
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authors.lastname: Shrestha
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authors.lastname: Sonett
authors.affiliation: 1 Department of Medicine and.
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authors.lastname: Hays
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authors.lastname: Oyster
authors.affiliation: 1 Department of Medicine and.
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Katz
authors.affiliation: 4 Department of Medicine.
authors.forename: Hilary
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authors.lastname: Robbins
authors.affiliation: 2 Department of Medicine and.
authors.forename: Melanie
authors.initials: M
authors.lastname: Brown
authors.affiliation: 1 Department of Medicine and.
authors.forename: Lorriana E
authors.initials: LE
authors.lastname: Leard
authors.affiliation: 6 Department of Surgery, University of California, San Francisco, San Francisco, California.
authors.forename: Jasleen
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authors.lastname: Kukreja
authors.affiliation: 5 Department of Surgery, College of Physicians and Surgeons, and.
authors.forename: Matthew
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authors.lastname: Bacchetta
authors.affiliation: 6 Department of Surgery, University of California, San Francisco, San Francisco, California.
authors.forename: Errol
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authors.lastname: Bush
authors.affiliation: 5 Department of Surgery, College of Physicians and Surgeons, and.
authors.forename: Frank
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authors.lastname: D'Ovidio
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authors.forename: Melanie
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authors.lastname: Rushefski
authors.affiliation: 4 Department of Medicine.
authors.forename: Kashif
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authors.lastname: Raza
authors.affiliation: 2 Department of Medicine and.|7 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Christie
authors.affiliation: 4 Department of Medicine.|8 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
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authors.lastname: Lederer
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D006233:Persons with Disabilities / Q000706:statistics & numerical data*; D005260:Female; D016330:Frail Elderly; D015577:Geriatric Assessment / Q000379:methods* / Q000706:statistics & numerical data*; D006801:Humans; D007334:Insulin-Like Growth Factor I; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D015995:Prevalence; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D015203:Reproducibility of Results; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D020738:Leptin; D018124:Receptors, Tumor Necrosis Factor; D007334:Insulin-Like Growth Factor I
keywords: biomarker; body composition; disability; frailty; lung transplantation