Discussion
While numerous reports have documented post-SLTx complications in the native lung, there is a dearth of studies focusing on their temporal progression, particularly in the context of fibrosis, thus underscoring the unique value of our investigation. This study centers on the analysis of temporal changes and complications in the native lung following ILD SLTx. Elicker et al. previously utilized a two-dimensional approach to assess native-lung capacity in recipients who had undergone SLTx for IPF, revealing a progressive volume loss over time [
6]. Conversely, with respect to recipients with systemic sclerosis-related interstitial pneumonia who had undergone SLTx, Hinze et al. categorized diverse chest CT findings into quintiles on the basis of severity and conducted a qualitative analysis concerning fibrosis [
7]. Our research introduces a novel semi-quantitative 3D evaluation method to more precisely quantify native-lung volume. Additionally, our investigation encompasses radiological qualitative analysis specifically dedicated to the assessment of lung fibrosis. Furthermore, our study scrutinizes pulmonary perfusion in the native lung following SLTx, revealing a progressive reduction in volume over time, concomitant with the deterioration of radiographic manifestations and a simultaneous decline in perfusion. Our analysis, alongside previous reports, suggests that ILD continues to slowly progress and erode its structural and functional integrity even after SLTx, supporting the notion that native-lung fibrosis continues to deteriorate despite high dosages of an immunosuppressive drug post-SLTx. While this is an anticipated phenomenon from a clinical standpoint, our study represents the first scientific endeavor to systematically evaluate and report on this aspect.
While there have been numerous reports of post-SLTx complications in the native lung, our analysis highlights specific concerns. It is evident from our investigation that the native lung is particularly susceptible to pneumothorax during the perioperative period and remains a source of persistent complications, including the development of pulmonary aspergillosis and acute exacerbation. Notably, these complications, unique to SLTx as opposed to BLTx, have raised concerns regarding the potentially greater complication burden associated with ILD SLTx. At times, complications in the native lung have prompted consideration of native-lung total resection, as indicated in past reports [
19]. Gonzalez et al. have reported pneumothorax as a complication that can occur in both the early and late phases following ILD SLTx, but they have concluded that it does not significantly impact long-term outcomes [
20]. In our analysis, 29.4% of SLTx recipients with ILD experienced pneumothorax, with a median time to onset of 2.0 months (IQR 0–46.5). Importantly, none of these recipients exhibited any adverse impact on graft function, and no cases were fatal because of native-lung pneumothorax.
On the other hand, post-SLTx aspergillus infection constitutes a severe complication. SLTx presents a higher incidence and mortality rates of pulmonary aspergillus infection than BLTx [
21]. This susceptibility extends beyond fungal infections and encompasses bacterial infections as well. Factors such as reduced mucociliary clearance, changes in sputum characteristics, and, in some instances, the establishment of chronic bacterial colonization may contribute to the predisposition to infections and their early dissemination [
22]. In our analysis, 11.8% of SLTx recipients with ILD were found to have developed pulmonary aspergillus infection in a native lung. While no fatalities were attributed to this infection, all cases necessitate life-long prophylaxis for the management of the native lung.
Post-SLTx recipients are reliant on graft lung function, and even when complications occur in the native lung, symptoms are often minimal, making acute exacerbations in the native lung easy to overlook. Goletto et al. reported cases of acute exacerbation in the native lung following infection with CMV and SARS-CoV-2 in two SLTx for IPF [
23]. Despite progressive fibrosis in the native lung, infection in the graft improved, and the recipients were discharged safely. Robert et al. also observed acute exacerbations in native lungs following CMV infection in three SLTx recipients for IPF, where the chest imaging revealed progressive fibrosis of the native lung with relative sparing of the allograft and the recipients survived [
24]. Our three cases of acute exacerbation were not related to infection but occurred when the overall condition of the recipients was compromised. Treatment interventions with steroids bolus were implemented, resulting in one recipient developing severe gastrointestinal complications, while another struggled with steroid-related adverse events due to the inability to reduce steroid dosage. Based on previous reports, acute exacerbation of the native lung after ILD SLTx may not be a direct cause of mortality, and it might be reasonable to opt for observation without intervention as long as it does not affect the graft, even when imaging findings rapidly worsen. However, it is a challenging decision to witness a rapid deterioration in imaging and take no action, which may necessitate further discussion. In any case, acute exacerbation of the native lung following ILD SLTx is a significant complication that cannot be ignored. It should be considered as an important complication of the native lung, and accumulating additional reports in the future will help advance our understanding.
Due to a severe donor shortage, the average waiting time in Japan exceeds 900 days, and the waitlist mortality rate surpasses 50%. Additionally, the absence of an allocation system considering disease progression after listing results in varying mortality rates depending on the underlying disorders [
3]. Consequently, the waitlist mortality rate is significantly higher for restrictive lung disorders such as ILD, while obstructive lung disorders such as LAM show a significantly lower rate [
8]. In Japan, although ILD has the highest number of listings, the transplantation rate is low. On the other hand, LAM, while being a severe condition, exhibits a remarkably low waiting list mortality rate, leading to a higher proportion of patients undergoing LTx. In this study, the disease distribution reveals LAM as the most prevalent with 35 cases, followed by 14 cases of IPF and 11 cases of CTD-ILD. Therefore, analyzing ILD vs. non-ILD in single-LTx might introduce an imbalance due to the inclusion of a large number of LAM cases in the non-ILD group. Consequently, differences in patient characteristics such as age, sex, and BMI may better reflect ILD in ILD SLTx and LAM in Non-ILD SLTx. In terms of long-term prognosis, LTx for LAM demonstrates superior outcomes compared to transplantation for other diseases, as highlighted by studies conducted by Khawar MU et al [
25] and Warrior K et al [
26]. However, in this study, although no statistically significant difference was observed in the long-term prognosis between ILD SLTx and non-ILD SLTx, the Kaplan-Meier method reveals that overall survival, freedom from CLAD, and CLAD-free survival for ILD SLTx are lower than those for non-ILD SLTx. This is presumed to be influenced by the higher prevalence of LAM cases in the non-ILD SLTx group.
While our study offers valuable insights into complications of the native lung following ILD SLTx, it is essential to recognize several limitations. Firstly, this research is based on a single-center retrospective analysis, potentially introducing selection bias and limiting the generalizability of our findings. Moreover, the relatively small sample size may impact the statistical robustness of our results. The limited number of events in the native lung further complicated the possibility of drawing definitive conclusions. Additionally, the analysis of SLTx versus BLTx for ILD was hindered by the small subset of ILD recipients (only eight) who had undergone BLTx, making a comparative assessment unfeasible. To enhance our understanding, reliance on existing literature was necessary to explore the prognosis of ILD recipients who had undergone LTx. Furthermore, it is important to acknowledge that the management and outcomes of complications can be influenced by various factors, including individual recipient characteristics and evolving medical practices. Lastly, our study did not delve into the potential impact of varying immunosuppressive regimens, which could be a significant factor in the development of complications.
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