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Updated: Aug 5, 2026
Intravital Two-Photon Microscopy of the Transplanted Mouse Lung
Published on: April 19, 2024
Machine learning analysis identifies key predictors of baseline lung allograft dysfunction and increased mortality in
Keerthana Sankar1, Laura DiChiacchio2, Yuri Matusov1
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Background:
Baseline lung allograft dysfunction (BLAD) is a phenotype of early graft dysfunction associated with impaired survival after lung transplantation. Although prior work links BLAD with several pre- and post-transplant factors, a robust set of donor and recipient predictors remains unclear.
Research Question:
What are important donor and recipient predictors of BLAD?
Methods:
We retrospectively reviewed 124 adults who underwent bilateral lung transplantation at a single center. Donor and recipient variables were evaluated using machine learning (gradient boosting and classification tree models), with high-importance predictors incorporated into logistic regression. Survival was assessed using Kaplan-Meier and Cox proportional hazards models.
Results:
BLAD occurred in 58 of 124 patients (46.7%). Our analysis identified 7 key factors associated with BLAD: Increased cold ischemia time (p = 0.04) and extremes of Body Mass Index (BMI) (p = 0.04) were associated with BLAD in a non-linear manner. Increased post-transplant Intensive Care Unit (ICU) length of stay (Odds Ratio [OR]: 1.08, 95% Confidence Interval [CI]: 1.00-1.17, p = 0.04) and donor tobacco use > 20 pack years (OR: 16.83, 95% CI: 2.34-121.2, p = 0.005) were also associated with higher odds of BLAD. Female sex (OR: 0.08, 95% CI: 0.02-0.39, p = 0.002), older age (OR: 0.93, 95% CI: 0.88-0.97, p = 0.003), and higher pre-operative Forced Expiratory Volume in 1 second (FEV₁) (OR: 0.19, 95% CI: 0.07-0.55, p = 0.002) were associated with lower odds of BLAD. The model demonstrated strong predictive performance (C-index 0.79, cross-validated). Patients with moderate to severe BLAD (Grade 2 and 3) had a significantly increased risk of death over a median follow-up period of 815 days (Hazard Ratio [HR] 3.53, 95% CI: 1.07-11.71, p = 0.04).
Conclusions:
BLAD is common after bilateral lung transplantation. Moderate to severe BLAD is associated with worse survival. Machine learning identified biological variables associated with BLAD and modifiable peri-operative variables, highlighting opportunities for pre-transplant and intra-operative optimization.
