Age In the Age of the Lung Allocation Score: Who Is at Greatest Risk of Death?

Cleveland Clinic researchers used a novel analytic strategy to study the role of age on lung transplant survival. Their results were both expected and surprising. As suspected, older recipients experienced lower survival, but younger recipients also experienced lower than expected survival. The researchers recently published their results in CHEST.

Age has been cited as a possible explanation for the decade-long plateau in five-year survival rates after lung transplant despite multiple innovations in pre- and post-transplant care. But studies addressing this hypothesis have lacked generalizability because of varying age classifications, center-specific practice variation and cohorts from outdated or mixed lung allocation systems.

“We are now transplanting sicker and significantly older patients than 10 years ago, due to the implementation of the lung allocation score [LAS], which prioritizes patients based on their risk of mortality on the waiting list. This could be a contributor to the post-transplant plateau in long-term survival,” says Maryam Valapour, MD, MPP, Director of Lung Transplant Outcomes at the Respiratory Institute, Senior Lung Transplant Investigator at the U.S. Scientific Registry of Transplant Recipients (SRTR) and senior author of the publication. “We discovered that the relationship between age and survival after transplant is not linear. Adult patients on either end of the age spectrum experience worse outcomes.”

Novel statistical methodology

Researchers used random survival forest (RSF) modeling as a complementary analysis that allowed them to validate findings from model-based analytic strategies. Traditional models by nature must make assumptions, and RSF does not require those assumptions. It also accounts for variable interactions and assesses for non-linear relationships.

The team assessed age as both a continuous and a categorical variable and only included patients from the SRTR during the period after the LAS system was implemented (May 2005) and before it was adjusted (Feb. 2015).

“We wanted to produce findings which were generalizable to all U.S. patients who receive access to lung transplant via the LAS system,” says Carli Lehr, MD, MS, a transplant pulmonologist in Cleveland Clinic’s Respiratory Institute and the paper’s first author. “Previous studies have looked at different transplant allocation eras and practice variations, and have included different categorical classifications of age, which limited how we could apply their findings to all patients in the U.S.”

The resulting cohort included 14,253 lung transplant recipients, with the following distribution in age categories: 7.7% younger than 30, 29.5% from ages 30 to 55 and 62.8% of patients over 55 years of age. Median age was 59 years, and median post-transplant survival was 5.6 years.

Similar risk, divergent pathways

The study findings confirmed previous research that older age increases risk of death after transplant. However, researchers were interested to discover that the youngest patients experience survival rates similar to the oldest patients. They also found that age was the most impactful risk factor across the board, and that the impact of age on survival increased with time post-transplant.

“We also found that different age groups experience increased mortality for different reasons. In the youngest group we studied, social determinants of health played a larger role than in other age groups,” says Dr. Lehr. Patients in the youngest age group also had higher LAS at the time of transplant than any other group, meaning that they generally had a higher severity of illness.

Is the LAS weighted toward older patients?

The LAS, first implemented in 2005, generates a composite score that ranks patients based on 1) their risk of death without a transplant and 2) their chance of survival with a transplant. The goal of the LAS is to allocate organs to those at the highest risk of death who are more likely to experience a survival benefit with transplant.

“Right now, the LAS gives more weight to waitlist mortality, which measures medical urgency. This tends to favor access for older adults due to their increased risk of death on the waiting list,” says Dr. Valapour. “We hope that our rigorous and novel analysis of age as a continuous variable demonstrates opportunities to tailor pre- and post-transplant interventions by age group to improve survival.”