Frailty Index for Lung Transplant CF Patients Helps to Predict Outcomes

Poorer score linked to graph failure, mortality risk

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A risk assessment dashboard shows the levels as very high.

Measures of frailty, based on an established index of physical activity, fatigue, weight loss, and the like for older adults, helps in predicting likely outcomes among cystic fibrosis (CF) patients listed for a lung transplant.

A greater degree of frailty linked significantly with worsening waitlist status, graft failure, and mortality, a study of CF patients who underwent lung transplants reported.

Assessing frailty, “common in this young population with advanced lung disease,” could help to identify those most at-risk and modify lifestyle factors to lessen their vulnerability and improve outcomes, its researchers noted.

The study, “Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation,” was published in the Journal of Heart and Lung Transplantation

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Lung transplant is considered for patients whose advancing lung disease is not adequately addressed by standard CF treatments. With an aging CF population, a greater risk of complications is associated with the procedure.

Predictive tools, particularly those specific to CF, are needed to stratify such risk for patients who might undergo a lung transplant.

Frailty and outcomes with a lung transplant for CF

Frailty refers to an age-associated increase in vulnerability for adverse health-related outcomes. The frailty index (FI) is used to evaluate various clinical variables, such as symptoms, co-existing conditions, disabilities, and laboratory tests to generate a frailty score, with a higher score indicating greater vulnerability to adverse outcomes.

FI values are known to correlate with mortality in the general population, particularly among older adults. But little is known about the prevalence of frailty in people with CF, who tend to be a younger population, and whether FI values might predict poorer outcomes among patients waiting for a lung transplant.

“Currently, we know little of the prevalence and impact of frailty in CF,” the researchers wrote.

A team of researchers developed a CF-specific FI to stratify the risk of negative outcomes after lung transplant in CF patients.

To create the index, the researchers studied data covering 188 CF patients, with a median age of 29.6, listed for a transplant in the Toronto Lung Transplant Program between 2005–15. Of this group, 176 received a transplant, after a median waitlist time of 69 days or about 2.3 months.

Patients were followed for a median of 5.3 years post-transplant. Survival at one year was 87.9%, 77.6% at three years, and 65.6% after five years.

Health status evaluations covering 66 items related to health history, like previous lung infections, lung function, pancreatic status, and gastroesophageal reflux; past treatments; and laboratory measures like body-mass index, walking speed, and blood pressure were used to develop the FI. The team also developed indices for lung disease severity and lifestyle/social vulnerability, which included a patient’s support system, smoking status, alcohol consumption, and employment and marital status.

At the time of transplant listing, 44.7% of the patients were considered frail, with an FI on the new scale of at least 0.25.

A higher FI associated significantly with a worsening waitlist status, meaning a patient died while on the list or was upgraded to the highest urgency status. FI scores higher than 0.25 also linked with longer hospital and intensive care stays, a greater risk of graft failure — when a person’s immune system rejects the transplant — and a higher mortality risk.

Ultimately, for every 0.1 increase in FI value, the risk of mortality after transplant rose by 74%, the researchers noted. Individuals with an FI score of at least 0.3 were 2.23 times more likely to die after transplant than those with scores less than or equal to 0.2.

In final analyses, the lifestyle/social vulnerability index also significantly associated with graft failure, and the lung severity index was associated with worsening waitlist status.

Researchers aimed to validate their FI in a separate group of 94 CF patients in Switzerland who underwent a transplant at centers there between 2008 and 2017. In total, 89 of these patients, who had a median age of 28, received a transplant after a median waitlist time of 284 days or about 9.5 months. Patients were followed for a median of 4.7 years after a transplant.

Post-transplant survival at one, three and five years was 93.2%, 88.4% and 77.9% among this group.

At the time of transplant listing, 21.3% of the patients were considered frail. FI values were significantly correlated with a worsening waitlist status and graft failure. Patients with FI scores between 0.2 and 0.3 were 4.3 times more likely to die post-transplant than those with an FI of less than 0.2.

“These results indicate that the FI provides clinically relevant information even in populations with significantly different characteristics allowing risk stratification for adverse outcomes and reinforcing the generalizability of this approach,” the researchers wrote.

While frailty is typically associated with advanced age, “our young cohort shows a frailty prevalence and median FI value corresponding to a much older population,” the researchers noted, adding that the finding is also “reflected in the disproportionally high mortality risk observed in our patients, compared with the general population.”

Routine frailty assessments in CF patients might help to identify those who are vulnerable, allowing for early interventions that could improve health outcomes, the researchers suggested.

“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,” the team concluded.