This retrospective study was conducted at [Author information withheld for anonymized peer review]. We reviewed data from 491 lung transplants performed between January 2013 and December 2023 (Figure 1). After exclusion of non-COPD cases, unilateral transplants, ex vivo lung perfusion (EVLP), re-transplantation, lobar transplants, pediatric recipients, cardiopulmonary transplants, and cases with incomplete data, a total of 130 COPD patients were included in the analysis. Patients were divided by predicted total lung capacity (pTLC) donor-to-recipient ratio into undersized (<0.9), size-matched (0.9–1.1), and oversized (≥1.1) groups, including 17 undersized, 67 size-matched, and 46 oversized patients. pTLC was calculated using equations established by the European Respiratory Society in 1995 [5]. For men, pTLC (L) = (7.99 × height [m] − 7.08); for women, pTLC (L) = (6.60 × height [m] − 5.79). The pTLC ratio thresholds were selected based on previous reports and our institutional experience, reflecting clinically relevant differences in outcomes across these ranges [6–8]. This retrospective study was approved by the Institutional Review Board of [Author information withheld for anonymized peer review] (approval number: PI 159/25, 7 July 2025). The requirement for informed consent was waived due to the retrospective nature of the study.

In Spain, the allocation of lungs is coordinated at the national level by the National Transplant Organization (ONT). Donated lungs are offered to candidate hospitals in order, considering the distance from the donor location. In selecting recipients, our institute considers criteria such as urgency, blood group compatibility, clinical factors (including age, infection status and hemodynamics), and size matching between donor and recipient. Size mismatch was not intentionally selected based on recipient characteristics, reflecting real-world allocation practices.

Bilateral lung transplantation was performed utilizing the sequential technique. Each native lung was removed one at a time via the clamshell or bilateral thoracotomy, and donor lungs were transplanted sequentially. Anastomoses of the bronchi, pulmonary arteries, and left atrium were performed with conventional methods. Extracorporeal life support (ECLS) was instituted when clinically indicated, including in cases of severe pulmonary hypertension, hemodynamic instability, hypoxemia, or hypercapnia. For oversized grafts, chest closure was performed cautiously to avoid graft compression, with consideration of delayed chest closure or graft size reduction when necessary. Postoperative ventilatory management was based on a lung-protective strategy, including low tidal volume ventilation and appropriate positive end-expiratory pressure, with early extubation whenever feasible. The immunosuppressive therapy includes basiliximab (20 mg) on Days 1 and 4 post-operatively, and a life-time triple immunosuppression regimen based on tacrolimus, mycophenolate mofetil and prednisone. Prophylactic antibiotic therapy is adjusted based on the bacterial species isolated from specimens taken from the donor and recipient at the time of surgery. Empirical administration of broad-spectrum antibiotics should be terminated after 7–10 days. For prophylactic antifungal therapy, liposomal amphotericin B (6 mL) is administered via nebulizer every 48 h until discharge, and once weekly thereafter. Follow-up included regular clinical visits, laboratory testing with monitoring of immunosuppressant levels, and spirometry. Visit frequency decreased progressively over time, from weekly after discharge to quarterly in the long term.

Demographic data collected for recipients included age, sex, height, body mass index (BMI), lung allocation score (LAS), secondary pulmonary hypertension, smoking history, cytomegalovirus (CMV) infection, previous thoracic surgery, arterial hypertension, diabetes mellitus, dyslipidemia, gastroesophageal, reflux disease, coronary artery disease, anti-human leukocyte antigen (HLA) antibodies, forced expiratory volume in 1 s (FEV₁), pretransplant medical condition—such as extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or non-invasive mechanical ventilation—intensive care unit stay prior to LTx, and pTLC.

For each recipient, donor demographic characteristics were also collected: age, sex, sex mismatch, height, BMI, type of donor, cause of death, duration of mechanical ventilation, arterial partial pressure of oxygen over fraction of inspired oxygen (PaO₂/FiO₂), smoking history, and pTLC.

Perioperative and postoperative outcomes included ischemic times for each lung, use of extracorporeal life support (ECLS), primary graft dysfunction (PGD) grading at 0, 6, 24, 48, and 72 h post-transplantation, rethoracotomy, postoperative ECMO, tracheostomy, duration of mechanical ventilation, intensive care unit (ICU) and hospital stay, and in-hospital mortality. Long-term outcomes included development of chronic lung allograft dysfunction (CLAD), time to CLAD onset, and survival at 30 days, 1 year, 3 years, and 5 years. PGD was assessed according to the International Society for Heart and Lung Transplantation (ISHLT) criteria (2005 consensus definition, revised 2017) [9, 10].

The incidence of PGD was analyzed as the primary outcome, and overall survival as the secondary outcome.

All statistical analyses were performed using GraphPad Prism 10 Software version 10.4.2 (GraphPad Software, Inc., San Diego, CA) and EZR version 1.68 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R version 4.4.2 (The R Foundation for Statistical Computing, Vienna, Austria) [11]. Statistical significance was evaluated using the Student’s t-test or the Mann–Whitney U-test for comparisons between two groups of continuous variables, depending on the normality of data distribution; one-way ANOVA followed by Tukey’s post hoc test or the Kruskal–Wallis test for comparisons among multiple groups of continuous variables; and Fisher’s exact test or the chi-squared test for categorical variables, depending on the size of the groups. Overall survival was defined as the period from transplantation to death from any cause, with patients who were still alive at the last follow-up considered censored. Kaplan–Meier estimates were used to generate survival curves, and differences between groups were assessed using the log-rank test. Multivariable analysis was performed using a Cox proportional hazards regression model, including variables considered clinically relevant. Statistical significance was defined as p < 0.05.

Recipient characteristics are shown in Table 1. The median pTLC ratios were 0.84 (IQR 0.82–0.89) in the undersized group, 1.02 (IQR 0.99–1.07) in the size-matched group, and 1.27 (IQR 1.16–1.36) in the oversized group. The oversized group had a higher proportion of female recipients (only 35% male; p < 0.001) and was significantly shorter (median height: 158 cm) with lower pTLC (4.70 L), contributing to graft oversizing. Secondary pulmonary hypertension was most frequent in the undersized group (p = 0.026). Other baseline factors were comparable across groups.

Donor data are summarized in Table 2. Male donors were more common in the oversized group (72%; p < 0.001), corresponding to higher male-to-female mismatches and higher donor pTLC (median: 6.54 L). Sex mismatch patterns varied significantly (p ≤ 0.001). No significant differences were found in other donor variables.

The incidence of PGD, the primary outcome of this study, is shown in Figure 2; Table 3. As illustrated in Figure 2A, both the undersized and oversized groups showed significantly higher PGD rates than the size-matched group at 6 and 24 h post-transplantation (p = 0.04 and p = 0.03, respectively). At later time points, only the oversized group remained significantly higher (p = 0.006 at 48 h; p = 0.017 at 72 h). Figure 2B presents grade 3 PGD incidence. Although early-phase differences were not significant (p = 0.08 at 0 h; p = 0.15 at 24 h; p = 0.2 at 48 h), the oversized group consistently showed higher rates. At 72 h, the undersized group had significantly lower incidence compared across the three groups (p = 0.03).

Other perioperative and postoperative outcomes are summarized in Table 3. The first and second graft ischemic times were significantly longer in the size-matched group compared to the other groups (p = 0.008 and p = 0.009, respectively). In contrast, no significant differences were observed regarding intraoperative ECLS, postoperative ECMO, tracheostomy, rethoracotomy, ventilation duration, ICU stay, or hospital stay. Mid-to long-term outcomes—including in-hospital mortality, CLAD incidence, and time to CLAD onset—were also comparable across groups.

Overall survival curves stratified by donor-to-recipient lung size group are shown in Figure 3. The median follow-up period was 6.23 years, estimated utilizing the reverse Kaplan-Meier method. Although the three-group comparison showed no statistically significant difference (p = 0.052), the undersized group demonstrated a favorable survival trend. Notably, pairwise comparisons revealed significantly better survival in the undersized group compared to both the size-matched (p = 0.018) and oversized groups (p = 0.045).

Furthermore, although the sample size was small, we performed a multivariate Cox regression analysis based on the available data variables (Table 4). The significance of the undersized group was maintained in the multivariate analysis as well.