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Frailty and Clinical Benefits with Lung Transplantation
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The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
Medicine, Alfred Hospital, Melbourne, Australia; 2Physiotherapy, Alfred Hospital, Melbourne, Australia. Purpose: There are accepted criteria for selection of candidates for LTx, however predicting who is likely to obtain a sustained benefit from this procedure is an evolving process. The concept of Frailty as a risk factor for poor outcome has been raised in the last few years. Frailty has been shown to be associated with poor outcome in other areas such as cardiac surgery and heart failure. We hypothesised that a higher frailty score would predict a worse outcome. Aim: To evaluate the Edmonton Frail Scale (EFS), six minute walk distance (6MWD) and grip strength as predictors of survival to transplant and outcome post LTx. Methods: Patients listed for LTx at a single institution were enrolled prospectively to undergo assessment with the EFS (previously validated in an Australian population), 6MWD and grip strength (with hand held dynamometer). These measurements were repeated every 3 months until transplantation or death on the waiting list. Outcome measures of ICU and hospital length of stay were used. Results were analysed using non parametric statistics. Results: 122 patients were recruited from February 2013 to July 2015. 91 patients were transplanted (58 COPD, 19 ILD, 6 CF, 4 PAH, 3 CLAD, 6 bronchiectasis), 14 died on the waiting list and 17 remain on the list. Survival post transplant was excellent with 100% at 3 months and 99% at 12 months. Higher Frailty score, lower 6MWD and lower grip strength were all predictive of death on the waiting list. Results are expressed as median and interquartile range. EFS: Transplanted (Tx) 6.0 (IQR 4-7) vs died prior (DP) 7.5 (IQR 5-9) p= 0.032. 6MWD: Tx 291 (IQR 201-369) vs DP 195 (IQR 162-240), p= 0.010. Grip strength: Tx 28.3 (IQR 21-36.5) vs DP 20.6 (IQR 14-29.1), p= 0.011. On univariate analysis none of these measures predicted ICU length of stay: Frailty score (p= 0.955), 6MWD (p= 0.853), and grip strength (p= 0.647) Nor total hospital stay: Frailty score (p= 0.797), 6MWD (p= 0.221), and grip strength (p= 0.541) Conclusion: The presence of frailty as defined by a higher EFS score, lower 6MWD and lower grip strength is associated with failure to survive to LTx, but not with early outcomes post LTx. This likely reflects the extremely complex nature of lung transplantation, and the many factors affecting early outcome. This study suggests the presence of frailty should not be a reason to reject listing for transplant, but rather a reason to expedite the process. 5( 7) Frailty and Clinical Benefits with Lung Transplantation D. Rozenberg ,1 S. Mathur,2 L. Wickerson,3 N.A. Chowdhury,4 L.G. Singer.1 1Medicine, Respirology, Lung Transplant Program, University of Toronto, University Health Network, Toronto, ON, Canada; 2Physical Therapy, University of Toronto, Toronto, ON, Canada; 3Physical Therapy, Lung Transplant Program, University of Toronto, University Health Network, Toronto, ON, Canada; 4Lung Transplant Program, University Health Network, Toronto, ON, Canada. Purpose: Fried frailty index (FFI) is a validated measure in lung transplant (LTx) candidates and is associated with pre-tx outcomes, but its association with post-tx outcomes is unknown. FFI contains parameters not readily available to clinicians. Study aims were: 1)To validate two alternate frailty phenotype models in LTx candidates. 2)To assess associations between pre-tx frailty and post-tx exercise capacity (6MWD), quality of life (HRQL) and 1 year mortality. Methods: For aim 1, 50 LTx candidates were prospectively evaluated for each of the 5 frailty attributes using the FFI and two clinical models(Table 1). Model 1 was from variables readily available to clinicians and Model 2 was from an existing dataset. Frailty was defined if ≥ 3 of 5 elements were present with agreement assessed using Kappa statistics. Construct validity was assessed using the London Chest Activity of Daily Living (LCADL) and Short-Physical Performance Battery (SPPB). Model 2 was then applied retrospectively to 226 LTx candidates listed from 1/04-6/09 who had both pre-tx rehab and HRQL (St.George’s Respiratory Questionnaire, SGRQ). Post-tx outcomes were compared between frail and non-frail patients using t-tests and regression analysis adjusting for age, sex, and diagnosis. Results: Frailty prevalence was 28-38% among the three indices. Kappa agreement between FFI and alternate models ranged from 0.34-0.41. All three indices were moderately correlated with LCADL (r= 0.42-0.60) and SPPB (r= -0.42 to -0.51). Frail candidates had worse Total SGRQ (72 ± 12 vs. 62 ± 13), p < 0.001. At 3-6 months post-LTx, frail candidates had a larger improvement with LTx in Total SGRQ (-47 ± 19 vs. -39 ± 20, p < 0.01) and 6MWD (153 ± 106
vs. 112 ± 104 m, p < 0.01), with differences persisting after adjustment. There was no difference in 1 year mortality (9% vs. 13%, p= 0.42). Conclusion: There was good construct validity and fair agreement among the frailty models. Despite significant disability pre-tx, frail LTx candidates demonstrated significant functional and HRQL benefit with transplantation.
Table 1: Fried and Clinical Frailty Models FRAILTY CHARACTERISTICS **Percentiles and ROC curves used for cut-offs.
Fried Frailty
Clinical Model 1
Shrinking Weakness
Weight Loss Grip Strength
Exhaustion
CES-D Depression Scale
Slowness
Gait Speed
Low activity
Physical Activity Questionnaire
BMI or Albumin BMI or Albumin Difficulty Opening Biceps Training Jar (Yes/No) Volumes Single Exhaustion SF-36 Vitality score Question (Yes/ No) Six-minute Walk Six-minute Walk Distance Distance Relative Physical SF-36 Physical Activity Question Function Score
Clinical Model 2
5( 8) Improvement in Frailty Is Associated with Improved Disability in Lung Transplantation J.P. Singer ,1 P. Shrestha,1 A. Soong,1 D. Huang,1 M. Mindo,1 L. Leard,1 J. Golden,1 S. Hays,1 K. Jasleen,1 R. Shah,1 D. Lederer,2 P. Katz,1 P.D. Blanc.1 1Medicine, UCSF Medical Center, San Francisco, CA; 2Medicine, Columbia University, New York, NY. Purpose: Frailty is associated with disability and poor health-related quality of life in lung transplant (LT) candidates. We tested whether frailty is independently associated with disability after LT. Methods: From 2/2010 to 9/2015, subjects were administered frailty and disability assessments before and at 3, 6, and 12 months post-transplant. We assessed frailty with the Short Performance Physical Battery (SPPB, range 0-12, lower scores denote increased frailty, Minimally Clinically Important Difference [MCID] = 1). We assessed patient-reported disability with the Lung Transplant-Valued Life Activities (LT-VLA) scale (range 0-3; higher scores denote worse disability; MCID = 0.3]). Using separate linear mixed models taking into account multiple observations and controlling for age, gender, and diagnosis, we estimated the impact of decreased SPPB (scaled to one point); an increase in FEV1 (scaled to 0.2L); and an increase in six minute walk distance (6MWD; scaled to 50m) on disability. We then combined all three independent variables plus covariates into a multivariate analysis. Results: In 161 subjects, a 1-point improvement in SPPB was associated with a 0.11 improvement in LT-VLA disability (-0.11; 95% CI: -0.13 to -0.08) (Table). This association was larger than that observed for 6MWD (-0.08, 95% CI: -0.10 to -0.05). Change in FEV1 was not associated with disability (-0.01, 95% CI: -0.03 to 0.01). In multivariate analysis, the association between SPPB and disability was not substantively changed (-0.09; 95% CI: -0.12 to -0.06; p< 0.05), whereas the association between 6MWD and disability was attenuated but still significant (-0.03, 95% CI: -0.05 to -0.01; p< 0.05). FEV1 remained unassociated with disability. Conclusion: In this prospective study, improvement in frailty is associated with reduced disability after lung transplantation, taking into account exercise capacity and allograft function. Interventions aimed at improving disability in lung transplant recipients should take frailty into account.
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
Medicine, Alfred Hospital, Melbourne, Australia; 2Physiotherapy, Alfred Hospital, Melbourne, Australia. Purpose: There are accepted criteria for selection of candidates for LTx, however predicting who is likely to obtain a sustained benefit from this procedure is an evolving process. The concept of Frailty as a risk factor for poor outcome has been raised in the last few years. Frailty has been shown to be associated with poor outcome in other areas such as cardiac surgery and heart failure. We hypothesised that a higher frailty score would predict a worse outcome. Aim: To evaluate the Edmonton Frail Scale (EFS), six minute walk distance (6MWD) and grip strength as predictors of survival to transplant and outcome post LTx. Methods: Patients listed for LTx at a single institution were enrolled prospectively to undergo assessment with the EFS (previously validated in an Australian population), 6MWD and grip strength (with hand held dynamometer). These measurements were repeated every 3 months until transplantation or death on the waiting list. Outcome measures of ICU and hospital length of stay were used. Results were analysed using non parametric statistics. Results: 122 patients were recruited from February 2013 to July 2015. 91 patients were transplanted (58 COPD, 19 ILD, 6 CF, 4 PAH, 3 CLAD, 6 bronchiectasis), 14 died on the waiting list and 17 remain on the list. Survival post transplant was excellent with 100% at 3 months and 99% at 12 months. Higher Frailty score, lower 6MWD and lower grip strength were all predictive of death on the waiting list. Results are expressed as median and interquartile range. EFS: Transplanted (Tx) 6.0 (IQR 4-7) vs died prior (DP) 7.5 (IQR 5-9) p= 0.032. 6MWD: Tx 291 (IQR 201-369) vs DP 195 (IQR 162-240), p= 0.010. Grip strength: Tx 28.3 (IQR 21-36.5) vs DP 20.6 (IQR 14-29.1), p= 0.011. On univariate analysis none of these measures predicted ICU length of stay: Frailty score (p= 0.955), 6MWD (p= 0.853), and grip strength (p= 0.647) Nor total hospital stay: Frailty score (p= 0.797), 6MWD (p= 0.221), and grip strength (p= 0.541) Conclusion: The presence of frailty as defined by a higher EFS score, lower 6MWD and lower grip strength is associated with failure to survive to LTx, but not with early outcomes post LTx. This likely reflects the extremely complex nature of lung transplantation, and the many factors affecting early outcome. This study suggests the presence of frailty should not be a reason to reject listing for transplant, but rather a reason to expedite the process. 5( 7) Frailty and Clinical Benefits with Lung Transplantation D. Rozenberg ,1 S. Mathur,2 L. Wickerson,3 N.A. Chowdhury,4 L.G. Singer.1 1Medicine, Respirology, Lung Transplant Program, University of Toronto, University Health Network, Toronto, ON, Canada; 2Physical Therapy, University of Toronto, Toronto, ON, Canada; 3Physical Therapy, Lung Transplant Program, University of Toronto, University Health Network, Toronto, ON, Canada; 4Lung Transplant Program, University Health Network, Toronto, ON, Canada. Purpose: Fried frailty index (FFI) is a validated measure in lung transplant (LTx) candidates and is associated with pre-tx outcomes, but its association with post-tx outcomes is unknown. FFI contains parameters not readily available to clinicians. Study aims were: 1)To validate two alternate frailty phenotype models in LTx candidates. 2)To assess associations between pre-tx frailty and post-tx exercise capacity (6MWD), quality of life (HRQL) and 1 year mortality. Methods: For aim 1, 50 LTx candidates were prospectively evaluated for each of the 5 frailty attributes using the FFI and two clinical models(Table 1). Model 1 was from variables readily available to clinicians and Model 2 was from an existing dataset. Frailty was defined if ≥ 3 of 5 elements were present with agreement assessed using Kappa statistics. Construct validity was assessed using the London Chest Activity of Daily Living (LCADL) and Short-Physical Performance Battery (SPPB). Model 2 was then applied retrospectively to 226 LTx candidates listed from 1/04-6/09 who had both pre-tx rehab and HRQL (St.George’s Respiratory Questionnaire, SGRQ). Post-tx outcomes were compared between frail and non-frail patients using t-tests and regression analysis adjusting for age, sex, and diagnosis. Results: Frailty prevalence was 28-38% among the three indices. Kappa agreement between FFI and alternate models ranged from 0.34-0.41. All three indices were moderately correlated with LCADL (r= 0.42-0.60) and SPPB (r= -0.42 to -0.51). Frail candidates had worse Total SGRQ (72 ± 12 vs. 62 ± 13), p < 0.001. At 3-6 months post-LTx, frail candidates had a larger improvement with LTx in Total SGRQ (-47 ± 19 vs. -39 ± 20, p < 0.01) and 6MWD (153 ± 106
vs. 112 ± 104 m, p < 0.01), with differences persisting after adjustment. There was no difference in 1 year mortality (9% vs. 13%, p= 0.42). Conclusion: There was good construct validity and fair agreement among the frailty models. Despite significant disability pre-tx, frail LTx candidates demonstrated significant functional and HRQL benefit with transplantation.
Table 1: Fried and Clinical Frailty Models FRAILTY CHARACTERISTICS **Percentiles and ROC curves used for cut-offs.
Fried Frailty
Clinical Model 1
Shrinking Weakness
Weight Loss Grip Strength
Exhaustion
CES-D Depression Scale
Slowness
Gait Speed
Low activity
Physical Activity Questionnaire
BMI or Albumin BMI or Albumin Difficulty Opening Biceps Training Jar (Yes/No) Volumes Single Exhaustion SF-36 Vitality score Question (Yes/ No) Six-minute Walk Six-minute Walk Distance Distance Relative Physical SF-36 Physical Activity Question Function Score
Clinical Model 2
5( 8) Improvement in Frailty Is Associated with Improved Disability in Lung Transplantation J.P. Singer ,1 P. Shrestha,1 A. Soong,1 D. Huang,1 M. Mindo,1 L. Leard,1 J. Golden,1 S. Hays,1 K. Jasleen,1 R. Shah,1 D. Lederer,2 P. Katz,1 P.D. Blanc.1 1Medicine, UCSF Medical Center, San Francisco, CA; 2Medicine, Columbia University, New York, NY. Purpose: Frailty is associated with disability and poor health-related quality of life in lung transplant (LT) candidates. We tested whether frailty is independently associated with disability after LT. Methods: From 2/2010 to 9/2015, subjects were administered frailty and disability assessments before and at 3, 6, and 12 months post-transplant. We assessed frailty with the Short Performance Physical Battery (SPPB, range 0-12, lower scores denote increased frailty, Minimally Clinically Important Difference [MCID] = 1). We assessed patient-reported disability with the Lung Transplant-Valued Life Activities (LT-VLA) scale (range 0-3; higher scores denote worse disability; MCID = 0.3]). Using separate linear mixed models taking into account multiple observations and controlling for age, gender, and diagnosis, we estimated the impact of decreased SPPB (scaled to one point); an increase in FEV1 (scaled to 0.2L); and an increase in six minute walk distance (6MWD; scaled to 50m) on disability. We then combined all three independent variables plus covariates into a multivariate analysis. Results: In 161 subjects, a 1-point improvement in SPPB was associated with a 0.11 improvement in LT-VLA disability (-0.11; 95% CI: -0.13 to -0.08) (Table). This association was larger than that observed for 6MWD (-0.08, 95% CI: -0.10 to -0.05). Change in FEV1 was not associated with disability (-0.01, 95% CI: -0.03 to 0.01). In multivariate analysis, the association between SPPB and disability was not substantively changed (-0.09; 95% CI: -0.12 to -0.06; p< 0.05), whereas the association between 6MWD and disability was attenuated but still significant (-0.03, 95% CI: -0.05 to -0.01; p< 0.05). FEV1 remained unassociated with disability. Conclusion: In this prospective study, improvement in frailty is associated with reduced disability after lung transplantation, taking into account exercise capacity and allograft function. Interventions aimed at improving disability in lung transplant recipients should take frailty into account.