Risk Stratification in Cystic Fibrosis Patients Listed for Lung Transplantation

In patients with cystic fibrosis (CF) listed for lung transplantation (LT), a frailty index based on standard multidisciplinary lung transplant assessment data facilitates patient risk stratification, calculating the risk of poor outcomes both post-transplant and during the waiting period. Results of a 2-pronged study that developed and validated this frailty index were published in The Journal of Heart and Lung Transplantation.

There is a need for predictors of survival for patients with CF listed for LT, study authors noted. Thus, a frailty index specific to CF that counts health deficits such as laboratory values, comorbidities, disabilities, and symptoms can be advantageous. Researchers therefore sought to construct a CF-specific deficit accumulation/frailty index for adverse waitlist and post-LT outcome risk stratification.

The investigators conducted a retrospective study involving 2 cohorts: a development cohort of patients on the waitlist at the Toronto LT Program (which includes Toronto General Hospital and St. Michael’s Hospital in Toronto, Canada) from 2005 to 2015; and a validation cohort of patients on the waitlist at Swiss LT centers (Zurich University Hospital, Lausanne University Hospital, and Geneva University Hospitals) from 2008 to 2017. The Toronto cohort, which had a medial waitlist time of 69 days, included 188 adult patients (176 [94%] of whom received transplants); the Swiss cohort, which had a median waitlist time of 284 days, included 94 adult patients (89 [95%] of whom received transplants). Median follow-up times post-transplant were 5.3 years and 4.7 years, respectively.

Researchers constructed and tested 3 indices based on deficits among patients in the Toronto cohort: a lung disease severity index based on 18 deficits; a frailty index based on 66 deficits; and a lifestyle/social vulnerability index based on 10 deficits. Deficits related to comorbidities, treatment, laboratory results, and social support at the time of LT listing. The researchers then evaluated how well index scores correlated with worsening waitlist status, length of hospital/intensive care unit stay, survival, and graft failure in the Swiss cohort. “Clinical parameters used for the indices were standard elements of CF and LT candidacy assessment recorded routinely in the charts when present,” study authors noted.

Further analysis found that risk stratification based on the frailty index was significantly associated with outcomes for waitlisted patients as well as those post lung transplant. Upon listing for LT, the frailty index identified 44.7% of patients in the Toronto cohort and 21.3% of patients in the Swiss cohort as frail (frailty index ≥0.25). In the Toronto cohort, the frailty index was significantly associated with all studied outcomes (frailty index and post-LT mortality, multivariable HR 1.74; 95% CI, 1.24-2.45 per 0.1 point of the frailty index); in the Swiss cohort, the frailty index was associated with worsening graft failure, post-LT mortality, and waitlist status.

Study limitations include the retrospective nature of the study as well as the large number of variables in the frailty index, which may limit its practical use in clinical settings that do not use medical records.

In summary, the investigators said that the frailty index developed in this study quantifies multidimensional patient assessment, “estimating patient vulnerability for adverse waitlist and post-LT outcomes.” They further noted that “A standardized assessment of the degree of frailty in CF can inform decision making, identify potentially modifiable risk factors, and potentially optimize patient follow-up and relevant translational research.” Further study of frailty in younger populations with advanced disease could offer additional insights on the effects of frailty and deficit accumulation on post-LT survival, study authors noted.

Reference

Koutsokera A, Sykes J, Theou O, et al. Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation. J Heart Lung Transplant. Published online July 23, 2022. doi:10.1016/j.healun.2022.07.017