Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation

Angela Koutsokera; Jenna Sykes; Olga Theou; Kenneth Rockwood; Carolin Steinack; Marie France Derkenne; Christian Benden; Thorsten Krueger; Cecilia Chaparro; John David Aubert; Paola Soccal Gasche; Christophe von Garnier; Elizabeth Tullis; Anne L. Stephenson; Lianne G. Singer

doi:10.1016/j.healun.2022.07.017

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation

Angela Koutsokera, Jenna Sykes, Olga Theou, Kenneth Rockwood, Carolin Steinack, Marie France Derkenne, Christian Benden, Thorsten Krueger, Cecilia Chaparro, John David Aubert, Paola Soccal Gasche, Christophe von Garnier, Elizabeth Tullis, Anne L. Stephenson, Lianne G. Singer

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11 Citas (Scopus)

Resumen

Background: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. Methods: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. Results: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. Conclusions: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Idioma original	English
Publicación	Journal of Heart and Lung Transplantation
DOI	https://doi.org/10.1016/j.healun.2022.07.017
Estado	Accepted/In press - 2022

Nota bibliográfica

Funding Information:
The authors would like to thank Mr Sassan Azad and Ms Karen Roman (Lung Transplant Program, Toronto General Hospital) for their contributions to the completion of the Toronto clinical dataset and Dr Rhea Varughese for her help with the data dictionary. We thank Mrs Audrey Roth and Mrs Fébronie Maillefer for contributing to the completion of the clinical dataset at the Lausanne University Hospital. We thank the patients who allowed their data to be captured in the databases and to be used for research. The protocol of this project was approved by the local ethics committees (study numbers for Switzerland 2018-00367, Toronto General Hospital 16-5344, St. Michael's Hospital 16-108) and by the Swiss Transplant Cohort Study (STCS - Project No 130). Although no STCS data were used for this study, we verified that none of the patients included in the Swiss cohort had refused to participate in the STCS which would indicate refusal to use their data for research. During this study, AK received support by the Swiss National Science Foundation (grants P300PB_164733 and P3P3PB_164734), the University Hospital of Lausanne (Fond de perfectionnement), the University of Lausanne (grant Pépinière) and the Research Fund of the Swiss Lung Association, Bern (grant 2018 -16). The funding sources had no role in study design, data collection, data analysis or writing of the report.

Funding Information:
During this study, AK received support by the Swiss National Science Foundation (grants P300PB_164733 and P3P3PB_164734 ), the University Hospital of Lausanne (Fond de perfectionnement), the University of Lausanne (grant Pépinière) and the Research Fund of the Swiss Lung Association, Bern (grant 2018 -16 ). The funding sources had no role in study design, data collection, data analysis or writing of the report.

Funding Information:
The protocol of this project was approved by the local ethics committees (study numbers for Switzerland 2018-00367, Toronto General Hospital 16-5344, St. Michael's Hospital 16-108) and by the Swiss Transplant Cohort Study (STCS - Project No 130). Although no STCS data were used for this study, we verified that none of the patients included in the Swiss cohort had refused to participate in the STCS which would indicate refusal to use their data for research.

Publisher Copyright:
© 2022 The Authors

ASJC Scopus Subject Areas

Surgery
Pulmonary and Respiratory Medicine
Cardiology and Cardiovascular Medicine
Transplantation

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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10.1016/j.healun.2022.07.017

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Koutsokera, A., Sykes, J., Theou, O., Rockwood, K., Steinack, C., Derkenne, M. F., Benden, C., Krueger, T., Chaparro, C., Aubert, J. D., Soccal Gasche, P., von Garnier, C., Tullis, E., Stephenson, A. L., & Singer, L. G. (Aceptado/En prensa). Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation. Journal of Heart and Lung Transplantation. https://doi.org/10.1016/j.healun.2022.07.017

Koutsokera, A, Sykes, J, Theou, O , Rockwood, K, Steinack, C, Derkenne, MF, Benden, C, Krueger, T, Chaparro, C, Aubert, JD, Soccal Gasche, P, von Garnier, C, Tullis, E, Stephenson, AL & Singer, LG 2022, 'Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation', Journal of Heart and Lung Transplantation. https://doi.org/10.1016/j.healun.2022.07.017

@article{3665ae5db23948eab9a84c7407700cfe,

title = "Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation",

abstract = "Background: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. Methods: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. Results: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. Conclusions: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.",

author = "Angela Koutsokera and Jenna Sykes and Olga Theou and Kenneth Rockwood and Carolin Steinack and Derkenne, {Marie France} and Christian Benden and Thorsten Krueger and Cecilia Chaparro and Aubert, {John David} and {Soccal Gasche}, Paola and {von Garnier}, Christophe and Elizabeth Tullis and Stephenson, {Anne L.} and Singer, {Lianne G.}",

note = "Funding Information: The authors would like to thank Mr Sassan Azad and Ms Karen Roman (Lung Transplant Program, Toronto General Hospital) for their contributions to the completion of the Toronto clinical dataset and Dr Rhea Varughese for her help with the data dictionary. We thank Mrs Audrey Roth and Mrs F{\'e}bronie Maillefer for contributing to the completion of the clinical dataset at the Lausanne University Hospital. We thank the patients who allowed their data to be captured in the databases and to be used for research. The protocol of this project was approved by the local ethics committees (study numbers for Switzerland 2018-00367, Toronto General Hospital 16-5344, St. Michael's Hospital 16-108) and by the Swiss Transplant Cohort Study (STCS - Project No 130). Although no STCS data were used for this study, we verified that none of the patients included in the Swiss cohort had refused to participate in the STCS which would indicate refusal to use their data for research. During this study, AK received support by the Swiss National Science Foundation (grants P300PB_164733 and P3P3PB_164734), the University Hospital of Lausanne (Fond de perfectionnement), the University of Lausanne (grant P{\'e}pini{\`e}re) and the Research Fund of the Swiss Lung Association, Bern (grant 2018 -16). The funding sources had no role in study design, data collection, data analysis or writing of the report. Funding Information: During this study, AK received support by the Swiss National Science Foundation (grants P300PB_164733 and P3P3PB_164734 ), the University Hospital of Lausanne (Fond de perfectionnement), the University of Lausanne (grant P{\'e}pini{\`e}re) and the Research Fund of the Swiss Lung Association, Bern (grant 2018 -16 ). The funding sources had no role in study design, data collection, data analysis or writing of the report. Funding Information: The protocol of this project was approved by the local ethics committees (study numbers for Switzerland 2018-00367, Toronto General Hospital 16-5344, St. Michael's Hospital 16-108) and by the Swiss Transplant Cohort Study (STCS - Project No 130). Although no STCS data were used for this study, we verified that none of the patients included in the Swiss cohort had refused to participate in the STCS which would indicate refusal to use their data for research. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

doi = "10.1016/j.healun.2022.07.017",

language = "English",

journal = "Journal of Heart and Lung Transplantation",

issn = "1053-2498",

publisher = "Elsevier USA",

}

TY - JOUR

T1 - Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation

AU - Koutsokera, Angela

AU - Sykes, Jenna

AU - Theou, Olga

AU - Rockwood, Kenneth

AU - Steinack, Carolin

AU - Derkenne, Marie France

AU - Benden, Christian

AU - Krueger, Thorsten

AU - Chaparro, Cecilia

AU - Aubert, John David

AU - Soccal Gasche, Paola

AU - von Garnier, Christophe

AU - Tullis, Elizabeth

AU - Stephenson, Anne L.

AU - Singer, Lianne G.

N1 - Funding Information: The authors would like to thank Mr Sassan Azad and Ms Karen Roman (Lung Transplant Program, Toronto General Hospital) for their contributions to the completion of the Toronto clinical dataset and Dr Rhea Varughese for her help with the data dictionary. We thank Mrs Audrey Roth and Mrs Fébronie Maillefer for contributing to the completion of the clinical dataset at the Lausanne University Hospital. We thank the patients who allowed their data to be captured in the databases and to be used for research. The protocol of this project was approved by the local ethics committees (study numbers for Switzerland 2018-00367, Toronto General Hospital 16-5344, St. Michael's Hospital 16-108) and by the Swiss Transplant Cohort Study (STCS - Project No 130). Although no STCS data were used for this study, we verified that none of the patients included in the Swiss cohort had refused to participate in the STCS which would indicate refusal to use their data for research. During this study, AK received support by the Swiss National Science Foundation (grants P300PB_164733 and P3P3PB_164734), the University Hospital of Lausanne (Fond de perfectionnement), the University of Lausanne (grant Pépinière) and the Research Fund of the Swiss Lung Association, Bern (grant 2018 -16). The funding sources had no role in study design, data collection, data analysis or writing of the report. Funding Information: During this study, AK received support by the Swiss National Science Foundation (grants P300PB_164733 and P3P3PB_164734 ), the University Hospital of Lausanne (Fond de perfectionnement), the University of Lausanne (grant Pépinière) and the Research Fund of the Swiss Lung Association, Bern (grant 2018 -16 ). The funding sources had no role in study design, data collection, data analysis or writing of the report. Funding Information: The protocol of this project was approved by the local ethics committees (study numbers for Switzerland 2018-00367, Toronto General Hospital 16-5344, St. Michael's Hospital 16-108) and by the Swiss Transplant Cohort Study (STCS - Project No 130). Although no STCS data were used for this study, we verified that none of the patients included in the Swiss cohort had refused to participate in the STCS which would indicate refusal to use their data for research. Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - Background: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. Methods: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. Results: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. Conclusions: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

AB - Background: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. Methods: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. Results: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. Conclusions: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

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U2 - 10.1016/j.healun.2022.07.017

DO - 10.1016/j.healun.2022.07.017

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SN - 1053-2498

JO - Journal of Heart and Lung Transplantation

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Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation

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