All patients who underwent lung transplantation between 06/2010 and 12/2019 at Hannover Medical School were included in the retrospective analysis. Lung recipients were divided in two groups: patients transplanted with lungs from donors <70 years and patients transplanted with lungs from donors ≥70 years. Outcome parameters, including pre-, peri-, and postoperative clinical parameters, as well as recipient overall survival and freedom from chronic lung allograft dysfunction (CLAD) were recorded and compared between the two groups.

All patients provided written informed consent for data utilization for scientific purposes at the time of listing for transplantation.

The primary composite outcome, graft survival, was defined as patient and graft survival and included patient mortality and the need for retransplantation. Primary graft dysfunction (PGD) was defined according to current International Society for Heart Lung Transplantation (ISHLT) guidelines (12).

Graft function was evaluated at regular outpatient visits and included surveillance biopsies as well as home spirometry testing. Predicted FEV1 was calculated for each recipient utilizing the formula FEV1 = race*((0.0395*height)−(0.025*age)−2.6). Since all recipients are Caucasian in the analyzed cohorts, ‘race’ was substituted by “1” in the formula. The measured FEV1 was then expressed as the %predicted FEV1.

CLAD was defined following current ISHLT guidelines as a persistent decline of FEV1 ≥20% from baseline in the absence of other conditions causing pulmonary impairment (13).

All donor organs were offered to our center by Eurotransplant. Within the regular LAS-based allocation process, organs were allocated for a specifc recipient, whereas organs in the rescue allocation process were accepted by the center and the recipient was chosen by the transplant center. Organ assessment and preservation were the same for lungs of donors <70 and of donors ≥70 years of age. Following endobronchial as well as macroscopic assessment of the donor lung during procurement, the donor organ was accepted by a surgical team from our center. Organs with irreversible macroscopic signs of parenchymal alterations such as emphysema were not accepted.

Recipient management at our institution has been previously reported and did not differ between groups (14). All recipient characteristics were recorded as previously reported and spirometry results were included after discharge following the initial hospital stay, 1 year after transplantation, and during the last follow-up visit at the outpatient clinic. Calculation of recipient-specific %predicted FEV1 was performed as previously reported (7). The clinical routine in our program includes, if hemodynamically necessary, intraoperative extracorporeal support using veno-arterial extracorporeal membrane oxygenation (ECMO) instead of conventional cardiopulmonary bypass (CPB). CPB is only used if additional cardiac surgery is performed, which is technically not feasible with ECMO (e.g., atrial septal defect closure). It should be noted that, as per our centre’s protocol, recipients with an underlying diagnosis of primary pulmonary hypertension received postoperative prolonged veno-arterial ECMO treatment for left ventricular remodeling as a planned treatment strategy (15).

Retrospective analysis of all parameters was performed using GraphPad Prism, Version 8.0 (San Diego, Ca, USA). Multivariate analysis was performed using SPSS 28.0.1.1 (IBM, Armonk, NY, USA).Variables are summarized as percentages, mean ± standard deviation (SD), or median (interquartile range, IQR). A Mann–Whitney U test was performed to test differences between continuous variables. Outcome-free survivals were calculated using the Kaplan-Meier method and were compared by using a log-rank test. p values < 0.05 were considered statistically significant.

A total of 1,168 patients underwent lung transplantation at Hannover Medical School between 06/2010 and 12/2019, of which 62 (5.3%) recipients received allografts from donors ≥70 years of age and the remaining 1,106 (94.7%) patients allografts from donors <70 years of age. The median follow-up was 8.9 years.

Patients who received lungs from donors ≥70 years of age were significantly older compared to recipients of organs from donors <70 years of age (median (IQR) 57 (54; 62) vs. 51 (36; 58) years of age; p < 0.0001). The body mass index of recipients who received organs from older donors was slightly higher than recipients of organs from younger donors (Table 1).

The distribution of transplant indications differed significantly between both groups. Organs from older donors were more likely to be offered to candidates suffering from chronic obstructive pulmonary disease (COPD) (40.3% vs. 27.6%, p = 0.04). In contrast, candidates with cystic fibrosis were more often transplanted with organs from younger donors (20.9% vs. 4.8%; p = 0.003). Lung retransplantation for CLAD was performed solely with organs from donors aged <70 years (p = 0.05) (Table 1).

The median lung allocation score (LAS; p = 0.18) and time on the waiting list (p = 0.56) showed no significant difference between groups.

Regarding the preoperative risk profile, no differences in the need for preoperative mechanical ventilation (3.2% vs. 3.3%; p < 0.99), preoperative ICU treatment (8.1% vs. 10.2%; p = 0.67), or preoperative ECMO (6.6% vs. 8.1%; p = 0.79) were observed (Table 1).

The median donor age in the ≥70 years of age group was 73 years of age (71; 75) vs. 47 years of age (34; 56) in the <70 years of age group, with a similar gender distribution between both groups (p = 0.19). Older donors had significantly shorter exposure to mechanical ventilation prior to procurement (3 (2; 4) vs. 4 (2; 7) days; p = 0.0007) but showed a higher Eurotransplant donor score compared to younger organ donors (8.7 ± 1.1 vs. 7.9 ± 1.6; p < 0.0001) (16). The oxygenation capacity (PaO₂ at 100% FiO₂, mmHg) of donors aged ≥70 years was higher compared to donors <70 years of age (412.5 (356; −469.5) vs. 384.0 (316; −448); p = 0.01). Additionally, older donors were less likely to have a smoking history compared to younger organ donors (12.9% vs. 42.1%; p < 0.0001). No organ donors aged ≥70 years of age showed signs of pulmonary contusion or aspiration (Table 2).

The majority of lung transplantations were performed as bilateral minimally-invasive surgeries, with no differences between groups. The need for extracorporeal support did not differ between groups (32.2% vs. 26.6% p = 0.38). Notably, the majority of patients requiring extracorporeal support intraoperatively were put on veno-arterial ECMO. Cardiopulmonary bypass was only used in a minority of cases, in which additional cardiac surgery was performed (2.1% vs. 1.6%; p = 0.80). The cold ischemic times of the first (p = 0.29) and second implanted lung (p = 0.91) did not differ between groups (Table 3).

The rates of postoperative ECMO were similar in both cohorts (9.7% vs. 9.4%; p = 0.94). The majority of these ECMO treatments resulted from our centre’s protocol for postoperative remodeling of the left ventricle in patients with severe pulmonary arterial hypertension (6.5% vs. 7.6%; p = 0.81) (15).

The primary graft dysfunction (PGD) score grade 3 at 24 h (p = 0.99), 48 h (p = 0.60) and 72 h (p = 0.94) after transplantation did not differ between groups.

Postoperative characteristics, including mechanical ventilation (p = 0.68), intensive care stay (p = 0.65), and total hospital stay times (p = 0.58), did not differ between groups (Table 3).

No differences in overall survival were observed between cohorts (p = 0.71) (Figure 1A), as measured at 1, 3, and 5 years (p = 0.21; p = 0.28; and p = 0.34) (Table 3). Patients who received lungs from donors aged ≥70 years showed no survival difference with respect to their underlying disease as compared to recipients of organs from younger donors in the same disease cohort (Figures 1B, C).

The incidence of CLAD did not differ between groups (Figure 2A). CLAD-free survival in recipients of organs from donors ≥70 years of age as compared to recipients of organs from donors <70 years after 3 and 5 years were 85.5% vs. 79.7% and 78.5% vs. 68.1%, respectively. Stratification of graft survival in patients transplanted for COPD and pulmonary fibrosis according to donor ages of <70 or >70 years did not differ between groups (Figures 2B, C).

FEV1 (%predicted) did not differ between groups at discharge (63.2% (52.2; 78.4) vs. 66.4% (55; 80.5); p = 0.29) (Figure 3A). One year after lung transplantation, recipients of organs from donors <70 years of age showed a significantly higher FEV1 (%predicted) as compared to recipients of lungs from donors aged ≥70 years (76.8% (63; 93.2) vs. 86.0% (70; 104); p = 0.03). This significant difference between both cohorts diminished in the following years after lung transplantation, showing similar %predicted FEV1 values at the last outpatient follow-up visit (70.5% (53; 87.3) vs. 73.3% (50; 94); p = 0.43) (Figure 3A). Stratification of FEV1 in patients with COPD and pulmonary fibrosis according to donor ages of <70 or ≥70 years did not show any difference between groups (Figures 3B, C).

In multivariable Cox regression analysis, which included multiple recipient- and donor-specific variables as well as procedure intraoperative variables (Table 4), donor age was not a risk factor for recipient mortality (p = 0.50) or the development of CLAD (p = 0.67) (Table 5).

Risk factors associated with recipient mortality included recipient age (p = 0.008), intraoperative utilization of ECMO (p < 0.001), and ischemic time of the first lung (p = 0.006). A donor history of smoking was identified as a risk factor for the diagnosis of CLAD (p = 0.001) (Table 5).