Assessing Short- and Medium-Term Outcomes of Lung Transplantation in Elderly Recipients: A Comparative Age-Based Analysis

Abstract

Background/Objectives: This study aims to analyze the short- and medium-term outcomes of lung transplantation (LT) in recipients aged 65 years and older, comparing them with those of younger individuals. The primary endpoints were 90-day and 1-year survival, while secondary measures included perioperative complications and chronic lung allograft dysfunction (CLAD) rates. Methods: A retrospective cohort analysis was conducted on 135 patients who underwent LT at the Siena Lung Transplant Center between January 2013 and December 2023. The participants were stratified into three age groups: under 60 years (Group Y), 60–65 years (Group M), and over 65 years (Group O). Outcomes assessed included ischemia times, transplant type (single or bilateral), ICU and hospital stay, postoperative complications, and CLAD incidence. The data were analyzed using non-parametric statistics, Kaplan–Meier survival curves, and correlation tests between clinical variables and survival outcomes. Results: Among the patients, 88 belonged to Group Y, 36 to Group M, and 11 to Group O. Idiopathic pulmonary fibrosis (IPF) was prevalent in older recipients (82%). Patients over 65 showed a lower prevalence of diabetes (p = 0.025) and pulmonary hypertension (p < 0.01). Bilateral LT was most common in Group Y (91%) and least in Group O (36%, p < 0.0001). Group Y had the longest maximum ischemia time (425 ± 161 min vs. 315 ± 140 min in Group O, p = 0.048). ICU stay (p = 0.289) and hospital stay (p = 0.900) did not differ significantly across groups. No group differences were observed in rates of primary graft dysfunction (p = 0.869), need for renal replacement therapy (p = 0.358), or prolonged ventilation (p = 0.609). CLAD incidence was comparable (p = 0.400), as were 90-day (p = 0.997) and 1-year survival rates (p = 0.174). Conclusions: Carefully selected patients over 65 years old can achieve similar short- and medium-term outcomes to younger LT recipients. These findings support the inclusion of older candidates in transplant programs, while highlighting the need for further research to optimize perioperative strategies and long-term management in this age group.

1. Introduction

Lung transplantation represents a vital treatment option for patients with end-stage lung disease, significantly enhancing both survival and quality of life. While lung transplantation was traditionally restricted to younger patients due to concerns about age-related comorbidities and postoperative complications, an increasing number of centers now consider patients aged 65 years or older for transplantation [1]. Traditionally, being over the age of 65 was viewed as a contraindication to lung transplantation, primarily due to the anticipated higher perioperative risks, reduced survival rates and the likelihood of comorbidities such as cardiovascular disease [2]. Considering the rising demand for lung transplants among elderly patients [3,4], the question of whether patients over 65 years of age represent valid candidates for lung transplantation remains pertinent. Previous studies have indicated that, while elderly patients may have a lower survival rate compared to younger cohorts, factors such as preoperative status, donor–recipient size mismatch [5], urgency of the transplant, and single-versus-bilateral transplantation significantly influence outcomes [6].

Moreover, there remains a substantial knowledge gap regarding the perioperative course and medium-term graft function in elderly recipients. Most prior studies have focused primarily on short-term survival, while secondary outcomes—such as the development of chronic lung allograft dysfunction (CLAD), duration of ICU/hospital stay, the need for renal replacement therapy (RRT), prolonged mechanical ventilation, and tracheostomy—have received comparatively less attention [7]. These outcomes are particularly relevant in older patients, who may be more susceptible to complications associated with prolonged immobilization, immunosuppression, or multi-organ dysfunction. Another important component of perioperative management is primary graft dysfunction (PGD), which is a major cause of early morbidity and mortality and has been linked to longer ICU stays and subsequent development of CLAD [7]. However, limited data exists on how PGD incidence and severity differ across age groups.

Recent technological and clinical advances, notably the refined use of extracorporeal membrane oxygenation (ECMO), have significantly improved perioperative support in lung transplantation. ECMO, particularly in veno-arterial or veno-venous configurations, is increasingly used as a bridge to transplant and intra/post-operative support. Selective and early application of ECMO has been associated with better hemodynamic control, improved oxygenation during surgery, and reduced PGD rates, even in higher-risk recipients [8]. Despite these improvements, concerns persist regarding elderly recipients, particularly due to chronic lung allograft dysfunction (CLAD) and other conditions, including an increased risk of neoplasms from continuous immunosuppression [9,10]. Consequently, more data is required to determine the ideal selection criteria and the long-term viability of lung transplantation in patients over 65. The primary outcome of this study is to compare 90-day and 1-year survival rates among lung transplant recipients across different age groups. Additionally, the study focuses on secondary outcomes, including perioperative variables, ICU and hospital stay, mechanical ventilation duration, CLAD incidence, RRT, and PGD, while also exploring how these factors correlate with overall outcomes. This comprehensive approach aims to refine the understanding of risk-benefit profiles in elderly lung transplant candidates and provide a foundation for improving candidate selection and perioperative strategies.

2. Materials and Methods

2.1. Study Conception

This single-centered retrospective cohort study included all lung transplant patients at the Lung Transplant Center of Siena University Hospital conducted between January 2013 and December 2023. Patients were categorized into three groups based on their age at the time of transplantation: Young Group (Y, <60 years), Mid-Age Group (M, 60–65 years), and Old Group (O, >65 years). This stratification was based on the existing literature [1,2], which indicates that individuals over 65 have higher perioperative risks. Our center does not list patients older than 65 years for lung transplantation. All patients in Group O were placed on the waiting list before reaching that limit. We introduced an intermediate group (60–65 years) to facilitate a comparison between this subgroup and patients over 65 years. This approach aimed to assess whether individuals who turn 65 while still on the waiting list should remain eligible for lung transplantation.

The primary endpoints of the study are 90-day mortality and 1-year overall survival (OS) analysis. Secondary endpoints include perioperative outcome comparison as type of transplant, ischemic times for each lung, postoperative complications, hospital and intensive care unit (ICU) stay length, need for prolonged mechanical ventilation (>96 h), tracheostomy or renal replacement therapy, incidence of primary graft dysfunction (PGD) and CLAD. Additionally, a correlation analysis was conducted within each group to assess the relationship between baseline and clinical parameters and postoperative outcomes.

Due to the retrospective, observational and anonymized nature of the study, the ethical approval of Siena IRB was not necessary to conduct the study. All patients provided informed consent at the time of listing for the use of their personal and clinical data for research purposes. All procedures were conducted in accordance with the ethical standards of the institutional and national research committees and the Helsinki Declaration (as revised in 2013).

2.2. Preoperative Evaluation

The selection process for lung transplant candidates follows a standardized protocol, incorporating comprehensive respiratory and cardiovascular tests, a whole-body CT scan and microbiological, osteometabolic, nutritional and psychological assessments. For patients over 60 years, the selection process for listing is more stringent. Candidates with ischemic heart disease, chronic renal failure, suboptimal metabolic-nutritional status or deteriorated autonomy are excluded. Single lung transplantation is preferentially allocated to patients over 60. However, it is not performed when primary or secondary pulmonary hypertension is diagnosed or if a confirmed lung infection is caused by multidrug-resistant pathogens. The decision between single lung and bilateral transplantation is made independently of donor organ quality. While managing a broad spectrum of conditions, most of our transplant recipients are affected by interstitial lung diseases and rare pulmonary disorders, for which our center serves as a national referral hub.

2.3. Surgical Approach and Postoperative Management

The surgical procedure is performed in a standardized fashion through a clamshell incision in bilateral cases or posterolateral thoracotomy for single ones [11]. Intraoperative ECMO is utilized selectively, primarily in a veno-arterial configuration. ECMO is preemptively initiated before pneumonectomy in cases of moderate-to-severe pulmonary hypertension. Alternatively, it is introduced intraoperatively in response to respiratory or hemodynamic instability. In cases of right ventricular dysfunction or prolonged graft ischemia, ECMO support is maintained postoperatively. The immunosuppression protocol, not influenced by the recipient’s age, consists of lifelong triple immunosuppressive therapy composed of corticosteroids, mycophenolate mofetil and either tacrolimus or cyclosporine. For all patients, spirometry was routinely performed during scheduled outpatient follow-up at 1, 3, 6, 9, and 12 months post-transplant, and every 3–6 months thereafter, or sooner in case of clinical deterioration. CLAD was defined in accordance with the updated ISHLT consensus guidelines, as a persistent decline in FEV₁ ≥ 20% from the post-transplant baseline, lasting for at least three months and not explained by acute rejection, infection, airway complications, or other reversible causes.

2.4. Statical Analysis

The variables were expressed as frequency and percentage, mean (standard deviation) or median (interquartile range). Non-parametric tests were adopted for data analysis: comparisons between two groups were determined by Mann–Whitney U test; ANOVA tests (Kruskal–Wallis and Dunn’s multiple tests) were performed to compare more than two groups. Contingency analysis was performed to evaluate the association and the independence between parameters and to calculate association measures. Correlations between variables were determined by Spearman correlation coefficient. The Kaplan–Meier method was used to estimate survival, stratifying patients by age group, censoring those who died while assuming similar lifespan projections for surviving patients. Statistical analysis was performed by GraphPad Prism 9.10.3 and XLSTAT 2021 software.

3. Results

3.1. Patient Characteristics

From January 2013 to December 2023, 135 patients underwent lung transplantation at our center. Mean age at transplantation was 52.0 (12.3) years. Eighty-three patients (61.5%) were male. The average waiting time on the transplant list was 358.5 (395.3) days. Bilateral lung transplantation was performed in 106 patients (78.5%). Of total, 88 (65.2%) patients were younger than 60 at the time of transplantation (Young Group, Y), 36 (26.7%) had 60 to 65 years (Mid-Age Group, M), 11 (8.1%) were older than 65 (Old Group, O). The median follow-up period was 621 days (255–1674). No patients were lost to follow-up. The characteristics of patients stratified by age groups are summarized in

Table 1. Patients’ characteristics.

Variables	Group Y (<60) (n = 88)	Group M (60–65) (n = 36)	Group O (>65) (n = 11)	p Value
Age (years)	47.0 (10.4)	62.3 (1.6)	65.5 (0.4)	<0.001
Male sex, n (%)	50 (56.8%)	25 (69.4%)	8 (72.7%)	0.307
End-stage disease, n (%)				<0.001
IPF	19 (22%)	18 (50%)	9 (82%)
COPD	14 (16%)	11 (30%)	2 (18%)
Cystic Fibrosis	24 (27%)	0 (0%)	0 (0%)
Other	31 (35%)	7 (19%)	0 (0%)
Body Mass Index, kg/m2	23.1 (4.5)	26.1 (4.5)	24.5 (4.1)	0.008
Smoker	38 (43%)	25 (69%)	9 (82%)	0.003
Comorbidities, n (%)
Cardiopathy	7 (8%)	3 (8%)	2 (18%)	0.650
Dyslipidemia	20 (23%)	18 (50%)	4 (36%)	<0.001
Arterial Hypertension	25 (28%)	14 (39%)	6 (55%)	0.158
Osteoporosis	56 (64%)	18 (50%)	10 (91%)	0.123
Diabetes	37 (42%)	8 (17%)	3 (27%)	0.025
Pulmonary hypertension	16 (18%)	16 (44%)	2 (18%)	0.005
MV/ECMO bridge n (%)	19 (22%)	0 (0%)	0 (%)	0.003
Admitted before transplant, n (%)	24 (27%)	1 (3%)	0 (0%)	0.002
Time on waiting list (days)	356 (410)	382 (408)	294 (202)	0.516

Data is shown as a percentage for categorical variables and as means with standard deviation when appropriate. Pairwise comparisons for continuous variables are provided in the Supplementary Materials (Table S1). IPF: idiopathic pulmonary fibrosis; COPD: chronic obstructive pulmonary disease; MV: mechanical ventilation; ECMO: extracorporeal membrane oxygenation.

.

The mean age at transplantation was 47.0 (10.4) years in Group Y, 62.3 (1.6) years in Group M, and 65.6 (0.4) years in Group O (p < 0.0001). Across all groups, there was a predominance of male patients: 50 (56.8%) in Group Y, 25 (69.4%) in Group M, 8 (72.7%) in Group O (p = 0.307). Smoking history was more prevalent in Group O (9, 82%) compared to Group Y (38, 43%) and Group M (25, 69%) (p = 0.003). The most common end-stage lung disease in Groups O and M was idiopathic pulmonary fibrosis (IPF), accounting for 18 cases (50%) in Group M and 9 cases (82%) in Group O, followed by chronic obstructive pulmonary disease (COPD, 11 cases, 30% in Group M and 2 cases, 18% in Group O). Cystic fibrosis was exclusively represented in Group Y (24 patients, 27%), which comprised the majority of other transplant indications (graft-versus-host disease, idiopathic pulmonary hypertension, and sarcoidosis; 31 patients, 35%, p < 0.0001). The prevalence of cardiovascular disease, arterial hypertension and osteoporosis did not differ significantly among groups. A significantly higher mean body mass index was observed in Group M (26.1 ± 4.5 kg/m²) compared to Group Y (23.1 ± 4.5 kg/m²) and Group O (24.5 ± 4.1 kg/m², p = 0.008). Diabetes mellitus was more prevalent in Group Y (37, 42%, p = 0.025). Dyslipidemia was most common in Group M (18, 50%) compared to 23% and 36% in Groups Y and O, respectively (p < 0.001). Pulmonary hypertension was significantly more frequent in Group M (16, 44%) compared to Group Y (16, 18%) and Group O (2 patients, 18%) (p = 0.005). No patients in Group O and only one patient (2.7%) in Group M were hospitalized at the time of transplantation due to worsening respiratory function, whereas 24 patients (27.3%) in Group Y were already hospitalized before lung transplantation (p = 0.0016). Additionally, no patients in Groups M and O were on mechanical ventilation or ECMO bridge therapy at the time of transplantation, whereas 19 patients (21.6%) in Group Y required such support (p = 0.0027). The mean waiting-list time was 356 (409.8) days in Group Y, 382 (408.0) in Group M and 293.6 (201.8) in Group O (p = 0.516). Table S1 in Supplementary File reported the pairwise comparisons of continuous variables between the three groups: Young Group (Y, <60 years), Mid-Age Group (M, 60–65 years), and Old Group (O, >65 years).

3.2. Surgical and Perioperative Outcomes

Table 2. Surgical and perioperative outcomes.

Variables	Group Y (<60) (n = 88)	Group M (60–65) (n = 36)	Group O (>65) (n = 11)	p Value
Bilateral transplant	80 (91%)	22 (61%)	4 (36%)	<0.001
Minimum ischemia time (min)	302 (130)	284 (89)	236 (76)	0.280
Maximum ischemia time (min)	425 (161)	350 (120)	315 (140)	0.048
In-hospital stay (day)	48 (47)	40 (18)	44 (25)	0.900
ICU stay (days)	18 (18)	13 (12)	15 (17)	0.290
CRRT	20 (23%)	4 (11%)	2 (18%)	0.358
PGD				0.869
0	21 (24%)	8 (22%)	3 (27%)
1	20 (22%)	6 (17%)	1 (9%)
2	21 (24%)	12 (33%)	4 (36%)
3	26 (29%)	10 (28%)	3 (27%)
Tracheostomy	29 (33%)	11 (31%)	2 (18%)	0.609
CLAD development	29 (33%)	16 (44%)	3 (27%)	0.400

Data is shown as a percentage for categorical variables and as means with standard deviation when appropriate. Pairwise comparisons for continuous variables are provided in the Supplementary Materials (Table S1). ICU: intensive care unit; CRRT: continuous renal replacement therapy; PGD: primary graft dysfunction; CLAD: chronic lung allograft dysfunction.

provides a detailed overview of surgical and postoperative outcomes, stratified by age.

Most patients in Group Y (80, 91%) and Group M (22, 61%) underwent bilateral lung transplantation, while a minority in Group O (4, 36%, p < 0.0001). The minimum ischemic time in minutes was 302 (103) in Group Y, 284 (89) in Group M, and 236 (76) in Group O (p = 0.280). The maximum ischemic time was significantly different between Group Y and Group M (p = 0.048), with values of 425 (161) minutes in Group Y, 350 (120) in Group M and 315 (140) in Group O. The length of hospital stay was similar among groups (χ² = 0.211, p = 0.900): Group Y had a mean stay of 48.1 (47.5) days, Group M averaged 40.2 (17.6) days, Group O 44.2 (25.3) days. Similarly, the length of ICU stay showed no significant variation (χ² = 2.479, p = 0.290), with Group Y patients spending a mean of 17.6 (18.3) days in ICU, Group M 12.7 (11.9) days, Group O 15.0 (17.2) days. No statistically significant differences emerged in post-transplant continuous renal replacement therapy (CRRT) use, with 2 cases (18%) in Group O, 4 cases (11%) in Group M, and 20 cases (23%) in Group Y (p = 0.358), nor in the occurrence of PGD (p = 0.869). Tracheostomy rates were comparable across groups, with 29 patients (33%) in Group Y, 11 patients (31%) in Group M, and 2 patients (18%) in Group O undergoing the procedure (p = 0.609). The incidence of CLAD did not differ significantly among the age groups (p = 0.400), with an incidence of 33% in Group Y, 44% in Group M, and 27% in Group O.

3.3. Survival and Outcome Correlation Analysis

The 90-day mortality rate was comparable across groups (p = 0.997, log-rank test, Figure 1): 14.9% in Group Y, 13.9% in Group M, and 9.9% in Group O. Similarly, no statistically significant difference was observed in the 1-year survival rates (p = 0.405, log-rank test, Figure 2).

Correlation analysis revealed some age group differences. In Group Y 1-year OS did not correlate with sex (χ² = 2.06; p = 0.151). No significant correlations were found between the type of transplant (single vs. double) and ICU stay (p = 0.642), hospital stay (p = 0.663), postoperative RRT (χ² = 0.872; p = 0.872), PGD rate (χ² = 4.29; p = 0.232), in-hospital mortality (p = 0.720) and 1-year OS (χ² = 0.442; p = 0.443). Single lung transplantation though showed a trend, not statistically significant, toward an increased CLAD rate, with 62.5% of patients undergoing single lung transplantation developing CLAD compared to 36.3% of bilateral cases (χ² = 3.48; p = 0.062). Additionally, single lung transplantation correlated with prolonged ventilation and tracheostomy as 75.0% of single lung transplant patients required tracheostomy while 28.6% of bilateral transplants did (χ² = 7.04; p = 0.008). Preoperative ventilatory or extracorporeal support did not correlate with 1-year OS (χ² = 4.04 × 10⁻⁴; p = 0.984) but did with ICU length of stay (p = 0.03). A strong positive correlation was observed between ICU stay and total hospital stay (rho: 0.577; p < 0.001). In Groups M no significant correlation was found between sex and 1-year OS (χ² = 0.042; p = 0.837). The type of transplant did not correlate with ICU stay (p = 0.123), whereas bilateral transplantation was significantly associated with a longer hospital stay (p = 0.035). No significant correlations were observed between the type of transplant and 1-year OS (χ² = 1.19; p = 0.275), RRT (χ² = 0.423; p = 0.515), PGD rate (χ² = 1.36; p = 0.716), in-hospital mortality (p = 0.540), tracheostomy (χ² = 0.088; p = 0.766) or CLAD incidence (χ² = 1.50; p = 0.221). A barely significant positive correlation was observed between ICU stay and hospital stay (p = 0.058). No significant correlation was found between time on the waiting list and total hospital stay (p = 0.208). In Group O, no significant correlation was found between sex and 1-year OS (χ² = 1.55; p = 0.213). However, the development of PGD showed a negative correlation with 1-year OS (rho coefficient = −0.573, p = 0.066), although it did not reach statistical significance. The type of transplant did not correlate with ICU stay (p = 0.705), hospital stay (p = 0.185), post-operative RRT (χ² = 0.196; p = 0.658), PGD rate (χ² = 2.00; p = 0.573), tracheostomy (χ² = 0.196; p = 0.656), in-hospital mortality (p = 0.428), CLAD rate (χ² = 0.016; p = 0.898) nor 1-year OS (χ² = 2.36; p = 0.124). No significant correlation was found between ICU stay and hospital stay (rho coefficient = 0.317; p = 0.342). Figures S1–S3 in Supplementary File reported the correlation matrix plots of continuous variables ICU stay, maximum ischemia time (min), minimum ischemia time (min), in-hospital stay (day), age (years) and time on waiting list (days) in the three groups.

4. Discussion

4.1. Age Difference, Disease Differences

Age categorization is not only a biographical figure but reflects important epidemiologic differences. IPF was the most common end-stage lung disease (82% of Group O and 50% of Group M). COPD was the second most common indication in older patients, aligning with the higher proportion of smokers (82%, p = 0.003) in Group O. In contrast, in younger patients a higher prevalence of cystic fibrosis (27%) and other conditions, such as graft-versus-host disease and idiopathic pulmonary hypertension (p < 0.0001) were observed. Our findings that IPF and COPD were the predominant indications for transplantation in older recipients are consistent with previous registry data and single-center studies [1,3]. As reported by Valapour et al. [3], IPF accounts for a growing proportion of transplants in elderly patients due to its age-related prevalence and disease trajectory. Similarly, the low rate of cystic fibrosis among older groups reflects its earlier disease onset and limited life expectancy without transplant, in line with data from the ISHLT registry [4].

Among patients over 65, there was a lower incidence of diabetes and pulmonary hypertension. Patients with such conditions are more likely to be excluded from the transplant program as they often present vasculopathy, coronary and right heart disease [2]. Overall, older patients tend to be in relatively better health than younger ones, reflecting the stringent selection attitude in this age group.

None of the patients in Group O and only one in Group M were hospitalized at the time of transplantation, compared to 24 patients in Group Y (p = 0.0016). Moreover, no patients over 65 underwent transplantation while on mechanical ventilation or ECMO bridge. This may reflect the slower progression of IPF and COPD in older adults [12], but again it emphasizes the stringent selection criteria for lung transplantation in elderly individuals. Specifically, we prioritize patients who are not severely immobilized, as frailty is a significant concern in older patients. Our approach is supported by our study findings, as correlation analysis in Group Y shows that while preoperative ECMO or mechanical ventilation does not correlate with 1-year OS, it influences ICU stay, which in turn correlates with total hospital stay. Presuming this observation would apply to patients over 60, and given that these patients are more susceptible to complications from prolonged hospitalization and immobility, we prefer to avoid transplanting patients requiring mechanical ventilation or ECMO in this population.

4.2. Bilateral vs. Single Lung Transplant

The surgical approach varied significantly among groups. Bilateral transplantation was highly prevalent in younger patients (91% in Group Y) and far less frequent in older patients (36% in Group O, p < 0.0001). This disparity is likely attributed to the higher perceived surgical risk and longer operative times associated with bilateral lung transplantation in older recipients [3]. Moreover, prolonged ischemia time is associated with an increased risk of developing PGD in lung transplant recipients [13]. In elderly patients, who are inherently more fragile, the development of PGD can lead to prolonged ICU stay and extended mechanical ventilation requirements, exponentially increasing the risk of potentially fatal complications. Therefore, the decision to perform single lung transplantation in elderly recipients is often driven by the need to reduce ischemia time, minimizing the risk of PGD and its associated complications [14]. We imply that thanks to shorter ischemia times, both minimum and maximum, in Group O, 110 min on average compared to Group Y, no significant differences were found in postoperative outcomes across groups.

These findings align with previous research indicating that older patients are more likely to undergo single lung transplantation due to concerns about surgical complexity and recovery, exhibiting lower morbidity and comparable early survival relative to bilateral lung transplantation [6]. In addition, given the lower life expectancy of older patients, they may not fully benefit from the long-term advantages associated with bilateral transplantation. In our correlation analysis, no significant differences in perioperative outcomes, including PGD rate, were observed among patients over 65 based on whether they received a single or bilateral lung transplant. These results support the use of single lung transplantation in older patients, an important consideration given the scarcity of optimal donor organs [15]. However, studies have demonstrated that bilateral lung transplantation can still be performed safely in carefully selected older patients, with outcomes comparable to younger recipients when appropriately chosen candidates undergo the procedure [6]. At our center, which has recently started performing lung transplants in patients over 65, we favor single lung transplantation whenever feasible, particularly in those with IPF. This approach is based on prior studies [16] showing that single lung transplantation for IPF offers a short-term survival advantage, as bilateral transplantation is associated with higher mortality rates within the first post-transplant year. This is partly due to the increased risk of PGD associated with bilateral transplantation. Correlation analysis in our study also confirmed that in patients over 65, PGD negatively correlates with 1-year OS, supporting single lung transplantation as a strategy for achieving favorable short-term outcomes. More recent studies have corroborated these findings, showing higher 90-day mortality following bilateral transplantation in older patients [7,17]. These considerations do not extend to patients under 60, where single lung transplantation is more frequently associated with prolonged ventilation and a higher incidence of CLAD, as previously reported [18,19]. In contrast, among patients aged 60–65, while most outcomes were comparable between single and bilateral transplantation, bilateral lung transplantation was associated with a longer hospital stay. This finding suggests that, given equivalent outcomes, reconsidering single lung transplantation in this age group could be beneficial, particularly to mitigate the risks associated with prolonged hospitalization.

4.3. Perioperative Complications, Recovery and Graft Survival

No significant differences in the length of hospital stay or ICU stay were observed between the age groups, which contrasts with some studies that suggest older patients typically require longer recovery times [20,21]. In our study, the mean ICU stay was 17.6 days for Group Y, 12.7 days for Group M, and 15.0 days for Group O (p = 0.2895), depicting a comparable recovery time across age groups. This finding is likely attributable to strict pre-transplant selection criteria for older patients, who were only listed and transplanted if in relatively preserved functional and nutritional status, and free of conditions such as frailty, renal dysfunction, or pulmonary hypertension. In contrast, the younger cohort included a higher proportion of patients requiring ECMO or mechanical ventilation as a bridge to transplant, which is known to prolong ICU recovery and may have counterbalanced the expected differences. These results suggest that selection factors and clinical condition at the time of transplant may play a greater role than chronological age in determining post-operative ICU needs.

The incidence of postoperative complications such as PGD and RRT did not differ significantly. The comparable rates of ICU stay, RRT, PGD, and tracheostomy between age groups support previous evidence that chronological age alone is not a predictor of worse perioperative outcomes, provided candidates are well selected. This aligns with reports by Ehrsam et al. [7], Hayanga et al. [22] and Biswa Roy [23], who demonstrated that selected elderly recipients can achieve morbidity profiles similar to younger patients. Considering older recipients, a not prolonged hospital stay contributes to a quicker recovery and a reduced risk of infectious complications, to which they are more vulnerable.

Survival analysis showed no significant differences in 90-day or 1-year survival across age groups (p = 0.997 and p = 0.174, respectively). This finding aligns with existing evidence suggesting that, when carefully selected, older patients can achieve survival outcomes comparable to those of younger recipients following lung transplantation [12,22,23]. The comparable 90-day and 1-year survival rates observed across age groups likely reflect differences in baseline comorbidities and selection criteria. Older recipients (>65 years) had a lower prevalence of diabetes and pulmonary hypertension, conditions known to negatively impact post-transplant outcomes. In contrast, younger patients (<60 years) included more individuals with severe disease trajectories requiring ECMO or mechanical ventilation pre-transplant—factors associated with prolonged ICU stay and early complications. These differences underscore the impact of rigorous selection in older candidates, which may offset age-related risk and explain similar survival despite chronological differences. Recent large-scale registry analyses from the UNOS database reinforce our institutional findings. Patients aged ≥70 years demonstrate high transplant rates, favorable perioperative outcomes, and comparable 90-day survival, despite a moderately increased long-term mortality risk (adjusted hazard ratio ~1.2–1.3) [24,25]. These data support the concept that, even in carefully selected septuagenarians, clinical strategies such as the use of extended criteria donors and donation after circulatory death, combined with strict preoperative screening, can lead to acceptable outcomes. However, the observed increase in long-term mortality highlights the ongoing need to focus on cardiovascular and oncological comorbidities, as well as frailty.

CLAD is a major long-term complication following lung transplantation. In this study, no significant differences were observed in CLAD rate across groups (p = 0.400), suggesting that recipient age alone may not be a determining factor in CLAD development. Previous studies also indicated that while older recipients may have higher perioperative risks, their long-term graft function is not necessarily inferior to that of younger patients when appropriately selected [18]. More in detail, we observed a non-statistically significant trend toward a higher incidence of CLAD in Group M (44%) compared to Group Y (33%) and Group O (27%). The higher rate in Group M may be due to the greater number of single lung transplants, which has been associated with a higher risk of CLAD [15]. In contrast, the lower CLAD incidence in Group O may be linked to the selective criteria applied to older recipients, ensuring better overall preoperative health. Interestingly, although our data show a trend toward increased CLAD in single lung transplants (especially in Group M), this is in line with prior work suggesting that bilateral transplantation may offer better long-term graft survival [18], though at the cost of higher early morbidity [16,17]. This trade-off reinforces the need for individualized surgical planning based on patient age, underlying disease, and expected benefit. Additionally, the lack of significant difference in CLAD incidence across age groups echoes findings from Hadjiliadis et al. [19] and Gerbase et al. [18], which suggest that long-term graft dysfunction may be more influenced by surgical technique and underlying disease than by age per se.

Based on our results, we recommend that patients over 65 years of age can be safely considered for lung transplantation, provided they meet stringent selection criteria. Specifically, candidates should have preserved functional status, no significant frailty, and absence of major comorbidities such as pulmonary hypertension, chronic renal failure, or uncontrolled diabetes. In this population, single lung transplantation appears to be a reasonable and effective approach, minimizing surgical burden without compromising short- and medium-term outcomes. Our findings support a carefully individualized, risk-adapted approach to patient selection, where chronological age alone should not be a contraindication to lung transplantation.

4.4. Limitations and Future Directions

This study has several limitations that should be acknowledged when interpreting the findings. First, the relatively small number of older recipients (n = 11) compared to the younger groups may limit the generalizability and statistical power, particularly for subgroup and correlation analyses. Additionally, the retrospective design introduces inherent limitations, including the risk of information bias and incomplete data capture, despite standardized clinical protocols.

We did not apply multivariable regression models to adjust for baseline differences between groups. This was a deliberate methodological choice: since patient selection criteria differ substantially with age, particularly due to stricter screening protocols for those over 65, these differences in baseline characteristics are inherently linked to the research question rather than representing confounding to be controlled. Moreover, the limited sample size, especially in the oldest group, restricts the statistical power needed for reliable regression analysis.

Moreover, this is a single-center study, which may reduce external validity due to center-specific protocols, surgical preferences (e.g., single vs. bilateral transplant), and follow-up procedures. Selection bias is also a consideration, as older patients were only transplanted if they met very strict eligibility criteria, potentially skewing the comparison in favor of older recipients.

Finally, the study focuses on short- and medium-term outcomes (90-day and 1-year survival) and does not provide data on long-term graft function or survival, which are essential for evaluating the full impact of lung transplantation in elderly recipients.

Future research should aim to refine selection criteria for older lung transplant candidates, incorporating a more comprehensive evaluation of comorbidities and frailty measures to optimize outcomes in this expanding patient population.

5. Conclusions

Lung transplantation in well-selected patients over 65 years old can achieve short-term survival outcomes comparable to younger recipients. Single lung transplantation appears to be a viable option for older patients, potentially reducing surgical risks and ischemic times. Future research should refine selection criteria, incorporating frailty assessments to optimize lung transplant outcomes in older recipients.