Inactive waitlist phenotypes and failure to survive to lung transplantation.

BACKGROUND

Inactive waitlist status is common in lung transplantation, but the extent to which distinct inactivity phenotypes identify candidates at risk of failing to survive to transplantation is uncertain.

METHODS

We analyzed adult U.S. lung transplant candidates listed from January 1, 2005, through March 31, 2026, using OPTN STAR files. Inactivity was characterized by cumulative inactive days, first inactivation reason, and cycling. Logistic models evaluated death or removal for being too sick; sequential severity adjustment, multiple imputation, 90- and 180-day landmark competing-risk analyses, and exclusion of initially inactive candidates assessed robustness.

RESULTS

Among 56,268 candidates, 16,301 (29.0%) experienced inactivity. Compared with candidate choice, temporary too-sick inactivation had the strongest association with death or too-sick removal in the original model (OR, 5.72; 95% CI, 4.88-6.71) and after full severity adjustment with multiple imputation (OR, 4.40; 95% CI, 3.74-5.17). At the 90-day landmark, adjusted subdistribution hazards increased across nonzero burden groups (sHRs, 1.25-1.45). At 180 days, burden greater than 10 days remained associated with subsequent risk (sHRs, 1.21-1.45), whereas greater than 0-10 days was not. Excluding 1354 candidates initially listed inactive did not materially change the too-sick estimate (OR, 5.83; 95% CI, 4.94-6.88).

CONCLUSIONS

Inactive status represents heterogeneous clinical and administrative phenotypes. Temporary too-sick inactivation remained strongly associated with failure to survive to transplantation after extensive severity adjustment, whereas landmark analyses separately demonstrated that sustained early inactive burden was associated with subsequent risk.