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.

Comparison of outcomes of chronic kidney disease based on etiology: a prospective cohort study from KNOW-CKD

“…This is particularly advantageous when the comparator groups are initially very different from each other and can achieve good balance and minimize the variances as shown in previous studies 15,16 . Several studies adopted this method to analyze the effect of sex, cancer type, monitoring or treatment on the outcome between groups with significant differences in baseline characteristics [16][17][18][19][20] . By employing this method, we could analyze the hazard ratio for the outcomes between two groups of CKD causes after adjusting for potential confounders.…”

Recipient donor sex combinations in solid organ transplantation and impact on clinical outcome: A scoping review

“…The incidence of acute rejection ranges between 4% and 28%, 70 with chronic lung allograft dysfunction seen in up to 40% of LuT recipients 71 . No differences were found in rejection rates among male and female recipients in a cohort of 203 patients 72 …”

“…71 No differences were found in rejection rates among male and female recipients in a cohort of 203 patients. 72…”

State-of-the-art Meeting on Sex and Gender in Transplantation: The Female Perspective

“…Despite a lower rate of primary graft dysfunction (possibly related to enhanced repair mechanisms), a sustained proinflammatory response is seen in female lung transplant recipients. 18 Preclinical mouse models suggest that the development of ABO blood group natural antibodies is significantly affected by sex and age, suggesting a potential role for sex hormones. 19,20 Mouse models allow the contribution of High-quality data to identify the proportion of transplant-eligible women and men on waitlists in different countries Understanding sex differences in pharmacokinetics and pharmacodynamics…”