Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation

Abstract

Background: Sex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men’s and women’s clinical and molecular responses to post-LTx IR. Methods: In 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression. Results: After adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h. Conclusions: Men and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.