Search Results (65)

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are clinically relevant pathogens in lung transplant (LT) recipients, but their impact on lung function and the benefit of ribavirin remains uncertain. We conducted a prospective multicenter observational cohort study of adult LT recipients with RSV or hMPV infection diagnosed between 2021 and 2024 at five centers, with follow-up for up to 12 months. Ribavirin was prescribed at the treating physician’s discretion. Multivariable analysis assessed the association between ribavirin and percentage change in forced expiratory volume in the first second (FEV₁) at 90 days, using FEV₁ three months before infection as baseline and adjusting for baseline FEV₁, pre-existing chronic lung allograft dysfunction, and time since transplantation. Seventy-six patients were included; 60 (78.9%) had RSV and 16 (21.1%) hMPV. Lower respiratory tract infection occurred in 48.7%, and an acute ≥10% FEV₁ decline at 14 days was observed in 29.3%. Among patients with lower respiratory tract infection, 45.9% received corticosteroids alone and 37.8% corticosteroids plus ribavirin. No statistically significant between-group differences in allograft dysfunction or mortality were observed. RSV and hMPV infections after LT were frequently associated with lower respiratory involvement and lung function decline. In this observational cohort, ribavirin use was not independently associated with 90-day FEV₁ change; however, residual confounding and limited statistical power preclude conclusions regarding treatment efficacy. Full article

Background: Lung transplantation (LTx) is the final therapeutic option for patients with end-stage irreversible respiratory failure. Chronic lung allograft dysfunction (CLAD) remains a major determinant of long-term outcomes, but early detection of functional decline may enable timely intervention and partial reversibility. Therefore, systematic monitoring of graft function is essential, and telemedicine-based spirometry may facilitate early identification of clinically relevant decreases in lung function. Objective: The aim of our study was to evaluate the feasibility of spirometry telemonitoring (TM) and its association with healthcare utilisation in lung transplant patients. Methods: This retrospective study compared lung transplant recipients: the first group underwent spirometry TM (n = 21), the second group was monitored with standard home spirometry (HS) (n = 23), and the control group underwent routine follow-ups only at the transplant centre (n = 32). Results: In the TM spirometry group, mean adherence was 62.7%, with 4957 examinations performed over a mean monitoring period of 252 days; 59.7% of FEV1 and 58.9% of FVC measurements were technically acceptable. Compared with routine care (RC), TM spirometry was associated with a shorter mean duration of both combined planned and urgent admissions (5.8 vs. 10.0 days, p < 0.001) and urgent admissions analysed separately (14.7 vs. 26.2 days, p < 0.001). Conclusions: TM spirometry was feasible and associated with lower healthcare utilisation in lung transplant recipients, supporting its potential value for post-transplant surveillance. Larger prospective randomised studies are needed to confirm these preliminary findings. Full article

Accurate donor–recipient allograft size matching remains a critical determinant of outcomes in lung transplantation, yet current approaches rely predominantly on predicted total lung capacity (pTLC) and height-based metrics derived from population-based equations. These simplified surrogates fail to capture individual anatomical variability, disease-specific alterations in thoracic geometry, and the spatial relationship between donor lungs and recipient chest cavities. In this review, we examine the limitations of conventional size matching and synthesize emerging evidence supporting imaging-based approaches, including computed tomography (CT) volumetry, radiomics, and machine learning. CT-derived volumetric analysis enables individualized anatomical assessment and has been associated with clinically relevant prediction of primary graft dysfunction and mortality. Advanced computational methods may further support the extraction of imaging-derived features and integration with clinical data, although these approaches remain investigational. Collectively, these developments signal a paradigm shift from crude population-based metrics toward imaging-driven and computational approaches in the modern era. With rigorous validation and careful clinical integration, imaging-based approaches may complement conventional size metrics and support more individualized donor–recipient assessment. Full article

Background: Habitual physical activity (PhA) may contribute to overall physiological reserve, yet its relevance for lung transplantation (LTx) remains unclear, as existing studies almost exclusively explore short-term exercise interventions. This study evaluates whether life-course PhA before LTx influences postoperative outcomes: functional capacity measured by 6 min walk test (6MWT), chronic lung allograft dysfunction (CLAD), and length of hospital stay (LOS). Methods: In this retrospective study, ninety-seven LTx recipients completed the Historical Adulthood Physical Activity Questionnaire (HAPAQ), assessing PhA from age 20 to transplantation. All participants were assessed within the same time frame, with varying time intervals since transplantation. Patients were classified into no/recreational/intensive sport groups based on regular participation. Statistical analyses examined sport group differences in 6MWT, CLAD, and LOS and interactions with sex, pulmonary disease type, and secondary pulmonary hypertension (PH). Results: Lifelong PhA did not significantly differentiate quantitative 6MWT, CLAD, or LOS, and no interaction effects were observed. A modest trend was noted in patients without secondary PH, among whom intensive PhA corresponded to more frequent within-norm qualitative 6MWT results. Outcomes were comparable between single- and double-lung (DLTx) recipients, although a moderate effect between sports groups suggested a possible DLTx compensatory advantage. Conclusions: This study provides the very first life-course assessment of PhA in LTx recipients, highlighting the value of HAPAQ for estimating pre-transplant physiological reserve. Despite postoperative outcomes being largely independent of lifelong PhA, and recovery appearing multifactorial, habitual PhA should not be overlooked in developing individualized prehabilitation strategies in transplant medicine. Full article

Chronic lung allograft dysfunction (CLAD) remains the principal limitation to long-term survival after lung transplantation (LT). Early molecular alterations within the graft may precede clinically overt functional decline, but their biological significance remains incompletely defined. In this single-center exploratory pilot study, 16 bilateral lung transplant recipients underwent bronchoalveolar lavage (BAL) sampling at 7 days, 15 days, and 3 months post-transplantation. BAL-derived microRNA (miRNA) profiles were analyzed longitudinally and correlated with long-term clinical outcomes, including CLAD development and phenotypic classification into bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), over extended follow-up (mean 98 months). Distinct early miRNA signatures were detectable within the first weeks after transplantation and were associated with divergent long-term clinical trajectories. Specific miRNAs, namely let-7e-5p and miR-30d-3p, were associated with subsequent CLAD, whereas differential expression patterns distinguished trajectories toward BOS or RAS. Enrichment analyses highlighted networks related to innate immune activation, hypoxia, tissue remodeling, and PI3K–mTOR signaling. Notably, the occurrence of acute rejection did not differ significantly between patients who developed CLAD and those who remained stable. These findings, although preliminary, suggest that early BAL-derived miRNA profiles may reflect biologically distinct graft states associated with long-term CLAD phenotypes. Full article

Background/Objectives: Chronic lung allograft dysfunction (CLAD) remains the leading cause of late graft failure after lung transplantation (LuTX). De novo donor-specific anti-HLA antibodies (dnDSA), especially HLA-DQ, have been implicated; we assessed associations between dnDSA (class and specificity) and CLAD after LuTX. Methods: We retrospectively analyzed all LuTX recipients transplanted from 2005–2018 at a single center (n = 585). dnDSA were measured by Luminex single-antigen bead assays (MFI > 1000) at 1, 3, 6, and 12 months and at least annually thereafter. CLAD was defined by ISHLT criteria; time-to-event comparisons used log-rank testing. Results: dnDSA developed in 151/585 recipients (25.8%), predominantly class II (129/585; 22.1%); class I dnDSA occurred in 52/585 (8.9%). CLAD occurred more frequently in dnDSA-positive than dnDSA-negative recipients (64/151; 42.4% vs. 109/434; 25.1%; p < 0.0001). Rejection-attributed death was higher in dnDSA-positive recipients (19/151; 11.3% vs. 25/434; 5.3%; p = 0.01). Both class I and class II dnDSA were associated with higher CLAD rates (log-rank p < 0.001 each). Locus-specific analyses identified HLA-DQ dnDSA as strongly associated with CLAD (p < 0.0001); DQ7 was the most frequent specificity (n = 44) and showed the strongest association (p < 0.0001). Conclusions: dnDSA after LuTX were associated with increased CLAD incidence and rejection-attributed mortality, with a prominent association for HLA-DQ—particularly DQ7. Full article

Lung transplantation provides a curative option for patients living with end-stage lung disease, with a goal of improving survival and quality of life. Chronic lung allograft dysfunction, or CLAD, represents a major cause of morbidity and mortality, particularly after the first year of transplant. Background/Objectives: The goal of this review is to outline the diagnosis and management of CLAD within the lung transplant population, as well as discuss future areas of potential research interest. Methods: A PubMed literature review of relevant publications regarding CLAD epidemiology, diagnosis, and management was performed to assess current understandings. Results: CLAD is the leading cause of death in lung transplant patients following the first year of transplant, and is common, with approximately 50% of patients exhibiting some degree of CLAD within five years of surgery. Well-established guidelines on diagnosis were recently published to aid clinicians in diagnosing and characterizing CLAD. Several medical and surgical interventions exist, although no therapy consistently and reliably stabilizes or reverses CLAD. Conclusions: CLAD management remains a priority within the lung transplant field as a leading cause of morbidity and mortality. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by progressive fibrosis and immune dysregulation, with lung involvement being a major cause of morbidity and mortality. Type V collagen (COLV), a cryptic self-antigen, has been implicated in the pathogenesis of fibrosis in both SSc and lung allograft dysfunction. To characterize the early histological, molecular, and immunological events associated with lung remodeling following immunization with COLV in a murine model (IMU-COLV), and to establish a temporal framework for fibrosis progression. Using a time-course design, lung tissue from IMU-COLV mice was analyzed at multiple intervals post-immunization. Histopathological assessment, immunohistochemistry, and gene expression analysis were performed to evaluate inflammation, endothelial activation, extracellular matrix remodeling, and collagen composition. We observed a progressive and spatially organized pattern of lung remodeling, beginning with peribronchovascular immune infiltration and culminating in airway-centered fibrosis. These changes were accompanied by dynamic endothelial activation, increased expression of profibrotic markers, and alterations in collagen architecture particularly involving COLV. The remodeling pattern closely mirrors histological features observed in early SSc-associated interstitial lung disease and other fibrotic conditions, such as idiopathic pulmonary fibrosis and chronic lung allograft dysfunsion. The IMU-COLV model recapitulates key early features of SSc-related lung fibrosis, highlighting COLV’s potential role as a driver of immune-mediated tissue remodeling. These findings provide a valuable platform for investigating the mechanisms underlying fibrogenesis and for testing targeted interventions in the early phases of pulmonary fibrosis. Full article

Background/Objectives: The use of intraoperative venoarterial extracorporeal life support (VA ECLS) has traditionally been used to support unstable patients undergoing complex lung transplantation. More evidence is emerging that the use of intraoperative VA ECLS may be beneficial for all patients undergoing lung transplantation. The aim of this study was to report the safety and feasibility of lung transplantation with the routine use of central VA ECLS. Methods: In this single-center retrospective observational study, all consecutive patients undergoing lung transplantation from April 2021 until September 2025 were included. Early outcomes and the incidence of primary graft dysfunction were evaluated with the International Society for Heart and Lung Transplantation criteria at 72 h after transplantation. Survival and chronic lung allograft dysfunction (CLAD)-free survival were reported with Kaplan–Meier estimates and 95% confidence intervals (CIs). Results: During the study period, 35 patients were successfully transplanted with the aid of central VA ECLS. There were no complications associated with intraoperative ECLS. One revision surgery was performed for immediate postoperative bleeding, and one for bronchial anastomosis air leak. Operative mortality occurred in three patients (8.6%). The median in-hospital stay was 30 (25–43) days. Severe primary graft dysfunction at 72 h was observed in four (11.4%) patients. Survival and CLAD-free survival at 1-, 3-, and 5-years following surgery were 85% (95% CI [74–98]), 74% (95% CI [59–92]), 67% (95% CI [28–82]), and 82% (95% CI [70–96]), 52% (95% CI [37–74]), 36% (95% CI [11–59]), respectively. Conclusions: Lung transplantation can safely be performed with the aid of central VA ECLS, with a low rate of primary graft dysfunction and favorable long-term outcomes. Further follow-up studies and greater experience are needed to make inferences on the long-term outcomes. This technique is relatively recent and evolving, representing an innovative intersection of advanced supportive technology with transplant surgery, potentially broadening indications and improving success rates. Full article

Severe discrepancy between availability of donor organs suitable for clinical transplantation and the proportion of patients on the waiting list has resulted in several clinical problems. First, waiting times for a suitable organ match have become increasingly long, leading to higher mortality while awaiting transplantation. Second, to address this issue, more “marginal” donor lungs have been used in the last two decades, inevitably leading to higher risk of perioperative and long-term complications. The ex vivo lung perfusion (EVLP) technology has been used to recondition marginal donor organs for clinical transplantation. There remains a further untapped pool of donor organs that are currently deemed too injured even for reconditioning via currently available EVLP strategies and are therefore discarded without reconditioning attempts. As the clinical use of EVLP has reached its full potential, further adjunct technologies, such as selective NET removal, cytokine removal and cell therapy techniques, may improve reconditioning outcomes and lead to increased number of donor organs transplanted. Moreover, NET removal may significantly improve donor organ quality and, therefore, the outcomes of recipients after lung transplantation. Such adjunct technology may also provide short- and longer-term benefits in reduction in early graft failure (primary graft dysfunction, PGD) and longer-term chronic lung allograft dysfunction (CLAD, previously known as chronic rejection) via more favorable early immune priming of organs. In this article we present current evidence and future perspectives on this novel intervention strategy that can be used on human donor lungs with the view to increase the utilization rate in lung transplantation in the near future. Full article

Motility disorders, particularly gastroparesis, are prevalent complications following solid organ transplantation, significantly impacting quality of life, nutritional status, graft survival, and mortality. This comprehensive review synthesises evidence from PubMed, Scopus, and Embase databases on pathophysiology, clinical manifestations, diagnosis, management, and prognostic factors across transplant types. Mechanisms include vagal nerve injury (highest in lung transplants, prevalence 40–91%), immunosuppressive effects (e.g., tacrolimus accelerates motility; mycophenolate impairs it), surgical trauma, microbiome dysbiosis (reduced Firmicutes/Bacteroidetes ratio), and metabolic factors like post-transplant diabetes (OR 5.17 in kidney recipients). Pediatric and thoracic recipients face the highest risks, with lung transplant gastroparesis conferring a 2.7-fold increased mortality/retransplantation hazard (p < 0.05). Diagnosis relies on gastric emptying scintigraphy (gold standard, sensitivity 85–95%) and wireless motility capsules (100% sensitivity for delay), while management encompasses prokinetics (60–80% response), endoscopic G-POEM (85% success), gastric electrical stimulation (100% quality-of-life improvement in series), and nutritional support. Prognostic factors include younger age (better intervention response), aetiology (anatomical worse than metabolic), and early therapy success. Outcomes vary: lung recipients experience severe impacts on chronic allograft dysfunction (83% oesophageal motility abnormalities correlate with 66–67% rejection). Future directions emphasise microbiome therapies, AI predictive models (AUC 0.85), and wearables for continuous monitoring. Multidisciplinary approaches are essential to balance immunosuppression with GI management, addressing ethical dilemmas like drug interactions and access disparities. Ultimately, early screening and personalised interventions can mitigate complications, enhancing long-term transplant success. Full article

Background/Objectives: Calcineurin inhibitors (CNI) contribute to renal dysfunction post-transplant. Belatacept is a renal sparing immunosuppressive agent. We sought to determine if the use of belatacept, as an alternative to a CNI-based maintenance immunosuppressive regimen ameliorates the effects of CNI-related nephrotoxicity in lung transplant recipients, while preserving graft function. Methods: Retrospective case series of adult lung transplant recipients (LTR) converted to belatacept with CNI elimination between 2020 and 2023. Primary outcomes were estimated glomerular filtration rate (eGFR) and pulmonary function testing. Secondary outcomes included incidence of rejection, mortality, donor specific antibody (DSA), chronic lung allograft dysfunction, infection, malignancies, and drug discontinuation. Results: Five LTR converted to belatacept with a median follow up of 3.49 years (IQR 16.4). eGFR improved with a median change of +18 mL/min/1.73 m² (IQR 6–34) at 12 months, this was sustained at last-follow-up (+19 mL/min/1.73 m² (IQR 6–34)). Force expiratory volume in 1 s (FEV1) declined from baseline to last follow-up (median change −0.53 L). At a median of 199 days post-conversion (IQR 108–453), belatacept was discontinued in 4/5 (80%) LTR, primarily due to graft dysfunction (3/4), and CNI therapy resumed. No LTR developed CLAD, DSA, malignancy, or died on belatacept. Infection (primarily pulmonary bacterial or fungal) occurred in all LTR on belatacept. Conclusions: Belatacept with complete CNI elimination in LTR resulted in a sustained improvement in renal function in this series but was accompanied by a high discontinuation rate due to worsening graft function. The risks to the graft associated with belatacept and calcineurin inhibitor elimination outweigh any potential renal benefits. Full article

Background/Objectives: Cytomegalovirus (CMV) infection is a frequent complication after lung transplantation, especially in high-risk donor-positive/recipient-negative (D+/R−) patients. CMV-specific hyperimmunoglobulin (CMV-HIG), administered either with antivirals or as monotherapy, may be beneficial for preventing or treating CMV infection in selected clinical scenarios. This study evaluated CMV-HIG indications and their impact on clinical outcomes in our lung transplant unit. Methods: We retrospectively analyzed adult lung transplant recipients (2010–2023) who received ≥2 doses of CMV-HIG for universal prophylaxis, monotherapy prophylaxis, preemptive therapy, or treatment of invasive disease. Results: CMV-HIG was administered to 204 out of 336 recipients (61%). CMV-HIG was well tolerated, with no treatment-related adverse events. Indications were preemptive therapy (63%), universal prophylaxis (24%), monotherapy prophylaxis (7%), and treatment of invasive disease (6%). CMV-HIG was well tolerated, with no treatment-related adverse events. No patients developed invasive disease during combination prophylaxis or preemptive treatment. The combination treatment of patients with invasive disease was also effective, and no cases of VGC resistance were detected. CMV-HIG monoprophylaxis has allowed us to delay or prevent viral replication in recipients who developed VGC side effects. Rates of acute rejection, Chronic Lung Allograft Dysfunction (CLAD), and overall survival were similar across CMV risk groups. Conclusions: Our results showed that the combined use of CMV-HIG and antiviral agents is effective in preventing CMV infection and disease in high-risk lung transplant recipients. This combination is also useful in treating invasive disease and preventing VGC resistance. Additionally, CMV-HIG monoprohylaxis can delay or prevent viral replication in recipients experiencing VGC-related side effects. These findings support the use of CMV-HIG in selected clinical settings, although prospective studies are needed to define its potential benefits within the current therapeutic armamentarium. Full article

Background/Objectives: Some lung transplant (LungTx) recipients do not achieve the expected lung function within the first year, a condition known as baseline lung allograft dysfunction (BLAD). Our objective was to analyze the risk factors associated with BLAD, focusing on the variables associated with a higher risk of developing a more intense alloimmune response. Methods: We carried out a prospective study including 88 LungTx recipients. BLAD was defined as failure to reach 80% of the predicted value for forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC) on two tests conducted at least three weeks apart. Tacrolimus time in therapeutic range (TTR) and mycophenolic acid area under the curve (MPA AUC_0–12h) were measured at the third month. Donor–recipient compatibility was assessed using HLA eplet mismatch analysis, performed via HLA Matchmaker 3.1. Results: BLAD patients showed greater eplet mismatch burden (67, IQR 20 vs. 55, IQR 22, p = 0.018) and had been exposed to a lower TTR (26.6%, IQR 14.0% vs. 39.6%, IQR 24.3%, p = 0.039) and less frequently to an adequate third-month MPA AUC_0–12 > 30 mg × h/L (57.1% vs. 89.2%, p = 0.020). DR/DQ eplet mismatches (β = −0.348, p = 0.002) and third-month MPA AUC_0–12 (β = 0.285, p = 0.009) were independently associated with six-month predicted FEV1%. Conclusions: Among other variables, BLAD and initial lung graft function are associated with greater eplet discordance and lower immunosuppressive drug exposure, suggesting a potential role of underlying alloimmune responses in their pathogenesis. Full article

Nowadays, there have truly been spectacular advances in surgical techniques, the preservation of organs for transplants, the optimal and efficient selection of both donors and recipients, a more efficient diagnosis and prediction of possible complications of transplants, and important progress in the advances of pharmacological immunosuppression protocols and procedures. In this sense, survival rates after transplantation of various organs have been progressively increasing, especially in the case of lung transplants, whose average survival rate is usually lower than that of other types of solid organ transplants. Thus, detecting acute and subclinical rejection and chronic allograft rejection of any implant is important. This is important in all transplants, such as heart and lung transplants. In this last type of transplant, particularly, and due to the chronic dysfunction of the lung allograft, it is key to detect rejection early and on time, since it can reach close to half of the transplant patient population. Therefore, practical diagnostic tools are needed to visualize the level of allograft damage using genomic methods such as those that measure donor-derived cell-free DNA, where its amount increases in the plasma component of the transplant after tissue injury or due to allograft infection. This biomarker has become a key element with light and hope, but with some shadows of caution due to its use as a panacea. Our research team has experience in solid organ transplantation in quantifying this parameter in the progression of the lesion of the implanted allograft, and our experience and comparison with the published literature will be presented in the following review, discussing validated and non-validated results. Full article