Are We Undersizing Allografts in Lung Transplantation for Chronic Obstructive Pulmonary Disease: An Analysis of the Organ Procurement and Transplantation Network Registry

S. Bakhtiyar¹, S. Y. Park², S. K. Randhawa³, E. A. David², R. A. Meguid⁴, J. D. Mitchell², A. L. Gray², J. R.H. Hoffman⁵, M. T. Cain^5
1University of California Los Angeles UCLA, Los Angeles, California ²University of Colorado, Aurora, Colorado ³University of Colorado Anschutz Medical Campus, Aurora, Colorado ⁴University of Colorado Denver School of Medicine, Aurora, Colorado ⁵University of Colorado, Denver, Colorado

Purpose: Optimal donor-recipient size-matching improves survival following lung transplantation (LTx) among patients with restrictive lung disease[1]. However, the evaluation of size-matching based on predicted total lung capacity among patients with chronic obstructive pulmonary disease (COPD) remains incomplete. We analyze a national cohort of LTx recipients to study this.

Methods: All adult (≥18 years) single and double LTx recipients with a diagnosis of COPD between 1987 and 2022 were identified in the Organ Procurement and Transplantation Network database. predicted total lung capacity (pTLC) was calculated for each donor and recipient using a previously validated equation [2]. Subsequently, donor-recipient predicted total lung capacity (D-RpTLC) ratios were calculated by dividing the donor pTLC by the recipient pTLC. A multivariable logistic regression with D-RpTLC parametrized as restricted cubic splines was developed to characterize the risk-adjusted association with post-transplant mortality. The cohort was then stratified based on D-RpTLC ratios, and post-transplant outcomes were compared between groups. Kaplan-Meier estimates were generated and graphically represented as unadjusted survival curves for each group. Additionally, Cox proportional hazards models were used to calculate estimates of the risk-adjusted hazards of mortality, with outcomes reported as hazard ratios [HR] and associated P-values.

Results: Of 11,720 LTx recipients with COPD, 266(2%) had D-RpTLC ratios < 0.8, 7,443(63%) between 0.8-1.2, 3,346(29%) between 1.2-1.6, 234(2%) of 1.6-2.0, and 431(4%) had ratios ≥2.0. Upon adjusted analysis of single LTx recipients and with a D-RpTLC ratio of 0.8-1.2 as reference, patients with a D-RpTLC ratio of 1.2-1.6 demonstrated superior 1-year survival (HR 0.76, P=0.03). While recipients with a ratio of 1.6-2.0 faced equivalent survival (HR 0.69, P=0.38), those with a ratio < 0.8 (HR 2.34, P=0.001) or ≥2.0 (HR 2.45, P=0.001) experienced greater 1-year mortality (Figure1A). Among bilateral LTx recipients and relative to a ratio of 0.8-1.2, patients with a D-RpTLC ratio of < 0.8 faced significantly greater 1-year mortality (HR 2.12; P=0.002). However, patients with a ratio of 1.2-1.6 (HR 0.89; P=0.33), 1.6-2 (HR 1.02; P=0.96), and ≥2.0 (HR 0.71, P=0.73) demonstrated similar 1-year survival (Figure1B). Importantly, for patients who survived the first post-transplant year, 10-year survival outcomes were similar for all D-RpTLC ratios (Figures1C,1D). No difference was observed in incidence of post-operative airway dehiscence, stroke, need for dialysis, graft-failure, acute allograft rejection, or primary graft dysfunction among recipients with D-RpTLC ratios from 0.8-2 (Table1). Secondary era-based analysis accounting for allocation policy changes did not change the primary conclusions.

Conclusion: Prior research demonstrated donor-recipient size-matching based on a D-RpTLC ratio of 0.8-1.2 was linked with improved survival outcomes among LTx recipients with restrictive lung disease. We demonstrate that in patients with COPD acceptable outcomes can be achieved with D-RpTLC ratio of up to 2, thereby expanding flexibility in donor allograft selection.

Identify the source of the funding for this research project: None