Increased delay to lung transplantation for women candidates: gender-based disparity matters in the lung transplant trajectory

Abstract

Background: Lung transplantation is a highly dynamic segment of solid organ transplantation in which gender plays a central role. Our objective was to investigate the causes of outcome differences between women and men all along the lung transplantation pathway.

Methods: We used data from the French COhort in Lung Transplantation (COLT) study (12 participating lung transplantation centres). Analyses were performed in three phases: baseline clinical characteristics, peri-transplantation period and post-transplantation follow-up.

Results: Overall, 1710 participants (802 women and 908 men) were included in this study. Women were less likely than men to undergo transplantation (91.6% versus 95.6%; p=0.001) and waited longer before transplantation (115 versus 73 days; p<0.001). Female gender and pre-transplantation class I anti-human leukocyte antigen antibodies were identified as independent factors associated with longer waiting time duration. Female transplant recipients commonly received lungs from height- and sex-matched donors, despite higher female waiting list mortality and a higher proportion of male donors. Importantly, women with oversized lung transplantation (defined by predicted total lung capacity (pTLC) ratio and weight mismatch) did not have worse survival. The overall post-transplantation survival of female recipients was significantly higher than that of male recipients (65.6% versus 57.3%; p<0.001), although the prevalence of specific major lung transplantation outcomes did not differ according to gender.

Conclusion: Women waited longer and were less likely to undergo transplantation. Women transplanted with an oversized lung did not have worse survival after transplantation, suggesting that size matching criteria based on pTLC ratio and weight mismatch may be less stringent in this context.

FIGURE 1

Patient flowchart. COLT: COhort in Lung Transplantation; CRISTAL: French Biomedical Agency database.

FIGURE 2

Underlying diagnosis in women and men awaiting lung transplantation. PAH: pulmonary arterial hypertension; ILD: interstitial lung disease. Chi-squared test used.

FIGURE 3

Waiting time before lung transplantation according to gender. a) Box plot representation of waiting time duration (log₁₀ applied; Wilcoxon test). b) Kaplan–Meier transplantation curves in men and women over 24 months (log-rank test). c) Multivariable Cox proportional hazards model showing factors associated with a shorter or longer (hazard ratio >1 or <1, respectively) waiting time duration before lung transplantation. Variables with p<0.2 in the univariable analysis were selected and a forward stepwise selection using Akaike Information Criterion was used for the final multivariable Cox model. ILD: interstitial lung disease; PAH: pulmonary arterial hypertension; HLA: human leukocyte antigen; CMV: cytomegalovirus.

FIGURE 4

Overall survival and chronic lung allograft dysfunction (CLAD) occurrence following lung transplantation according to recipient gender. a) Kaplan–Meier survival curves over 8 years between women and men (log-rank test). b) Comparison of CLAD occurrence between women and men over 8 years (log-rank test). c) Multivariable Cox proportional hazards model showing factors associated with a shorter or longer (hazard ratio >1 or <1, respectively) survival. Variables with p<0.2 in the univariable analysis were selected and a forward stepwise selection using Akaike Information Criterion was used for the final multivariable Cox model. PAH: pulmonary arterial hypertension; ILD: interstitial lung disease; EBV: Epstein–Barr virus.

FIGURE 5

Factors influencing survival after lung transplantation. a) Survival curves according to donor versus recipient gender combinations over 8 years (log-rank test). D_M: man donor; D_W: woman donor; R_M: man recipient; R_W: woman recipient. b) Survival curves according to weight mismatch (donor weight minus recipient weight). c) Survival curves according to donor-to-recipient predicted total lung capacity (pTLC) ratio. d) Survival curves according to age (in women recipients only).