Citations

Background: The role of venous Doppler ultrasound in assessing venous congestion in the setting of post-lung transplantation surgery is unknown. We performed a feasibility study on the use of venous Doppler ultrasound in the immediate post-operative period after lung transplantation in a retrospective, single-center observational evaluation. Patients had at least two venous congestion Doppler ultrasound exams involving interrogation of IVC diameter, hepatic vein, portal vein and renal vein Doppler assessments. Results: A total of 9 patients were included in our study with a median age of 60 years, 66.7% being male, and a median BMI of 20.9. All patients had VExUS grade ≥1 on their first venous Doppler exam. All nine patients had a decrease in portal vein pulsatility from initial to final exams. Correlation between portal venous pulsatility and net fluid balance was not statistically significant R= 0.33 (P= 0.39). Other parameters, including VExUS grade, IVC diameter, HV and RV Doppler changes from initial to final ultrasound exams showed variable changes in the post-operative period. Conclusion: Venous congestion Doppler ultrasound assessments appear feasible in immediate postoperative lung transplant patients. A multitude of factors beyond fluid status likely affect waveforms.

Purpose Mycobacterium avium complex lung disease (MAC-LD) represents the most common form of nontuberculous mycobacterial lung infection, particularly affecting women and older adults. Clinical management remains challenging, including prediction and differentiation between progressive and non-progressive disease. Overexpression of PD-1 pathways have been reported in progressive disease, and we hypothesize that PD-1 inhibition can restore antigen-specific immune responses detectable by FluoroSpot assay. Methods Peripheral blood mononuclear cells from 22 participants, including progressive and non-progressive MAC-LD patients, healthy controls, and individuals with latent tuberculosis infection (LTBI) were stimulated with nontuberculous mycobacteria and Mycobacterium tuberculosis antigens. Cytokine secretion of interferon-gamma (IFN-γ) and interleukin-2 (IL-2) were quantified using dual FluoroSpot assay, with and without PD-1 blockade. Results Progressive MAC-LD cases demonstrated significant increases in glycopeptidolipid (GPL)- and PPD-stimulated IFN-γ responses following PD-1 blockade, which was not seen in healthy controls, LTBI, or non-progressive MAC-LD patients. After GPL stimulation and in the presence of anti-PD-1, the number of IFN-γ responses increased from 25% to 75% in samples from progressive MAC-LD patients. This supports an association between PD-1–mediated T-cell dysfunction and disease progression. Mycobacterial MTB300 peptide pool antigen failed to discriminate MAC-LD from healthy controls, underscoring antigen specificity. Conclusions Our pilot study demonstrates that IFN-γ FluoroSpot assays, particularly when combining GPL or PPD stimulation and PD-1 inhibition, may help identify progressive MAC-LD. These findings also support other studies reporting that immune checkpoint dysregulation can be present in some patients with progressive and severe MAC-LD patients. Additional studies are warranted to determine its pathogenic role.

Introduction Studies have revealed circadian rhythms affect many organ systems and time of injury can impact healing, lung function, and inflammation. We hypothesized operative time may impact post-operative risk. Accordingly, the aim of this study was to compare post-operative complications in patients whose surgery started and finished before 12pm (Group 1); after 12pm (Group 2); and started before 12pm and finished after 12pm (Group 3). Methods Patients from two previous prospective studies were included in this post-hoc analysis. Inclusion criteria were indication for lung resection surgery (confirmed or highly suspicious tumor), age ≥18 and ability to undergo cardiopulmonary exercise testing (CPET). Exclusion criterion was inability to perform surgery (either low predicted postoperative oxygen consumption or inoperability). All patients underwent pre-operative CPET and spirometry. Post-operative pulmonary (PPC) and cardiovascular complications (PCC) were prospectively assessed from the hospital stay up to 30 days. Results Data from 497 patients were analyzed. On comparison of groups, there were differences in BMI (highest in Group 3), surgery duration (lowest in Group 1) and frequency of lobectomies (lowest in Group 1). Incidence of PPC was lowest in Group 1 (n=17; 9%) compared to n=17 (21%) in Group 2 and n=37 (17%) in Group 3 (p=0.01). Incidence of PCC was lowest in Group 1 n=25 (13%) compared to n=19 (23%) in Group 2 and n=46 (21%) in Group 3 (p=0.05). Multivariate logistic regression adjusted for confounders (BMI, surgery duration and lobectomy) showed time of surgery after 12pm was independently associated with PPC with OR = 2.17 (95% CI 1.07-4.41); p=0.03. Conclusion Time of surgery may impact the incidence of PPC in lung resection surgery patients with highest risk in patients undergoing the surgery after 12pm.

Abstract Purpose This analysis aims to provide a comprehensive overview of lung transplantation trends in the United States from January 1, 1988, through January 31, 2025. By examining key variables such as recipient ABO blood group, donor type (deceased or living), demographic factors, and geographic distribution, the goal is to highlight the evolution and current state of lung transplantation practices. Methods Data were obtained from the Organ Procurement and Transplantation Network (OPTN), encompassing all reported lung transplants during the specified time period. Relevant metrics included the number of transplants per year, recipient characteristics (blood type, race/ethnicity, gender, and age), donor type (deceased versus living), and state-level transplant volumes. Simple descriptive statistics (e.g., frequencies and percentages) were used to identify trends and capture the distribution of transplants among different demographic groups and geographic regions. Results A total of 55,435 lung transplants were performed in the United States between 1988 and early 2025. The vast majority (over 99%) utilized deceased donors, underscoring the limited role of living-donor lobar transplantation, with only 253 procedures reported nationally. Among recipients, ABO blood group O was the most common (∼45%), followed by group A (∼40%), group B (∼11%), and group AB (∼4%). Male recipients represented approximately 57% of transplants, while females accounted for 43%. Regarding race/ethnicity, White non-Hispanic patients constituted roughly 80% of all recipients, with Black non-Hispanic (8%) and Hispanic/Latino (8%) recipients forming smaller but significant proportions. Age distribution data revealed that individuals aged 50 to 64 years received nearly half of all lung transplants, and those over 65 years composed about a quarter of total recipients, reflecting a gradual shift in acceptance criteria favoring older adults. Geographically, California reported the highest volume of lung transplants, attributable to its large population and multiple high-volume transplant centers, while other states such as Florida, Ohio, North Carolina, and Missouri also demonstrated notable activity. Conclusion Lung transplantation in the United States has witnessed substantial expansion in both volume and scope since 1988, with the majority of procedures involving deceased donor lungs. A small number of living-donor lung transplants, while demonstrating innovative clinical possibilities, remains limited. The demographic profile of recipients continues to shift, evidenced by a growing proportion of older adults and a predominance of ABO type O and White, non-Hispanic recipients. Despite these advancements, persistent gaps in access, particularly among underrepresented racial and ethnic groups, highlight the need for further refinement in organ allocation policies and broader support services. This abstract is funded by: None

Abstract Rationale Acute cellular rejection (ACR) within first-year post-lung transplantation has important implications for prognosis. Calcineurin inhibitors (CNI), including tacrolimus or cyclosporine, along with cell cycle inhibitors (CCI) and steroids, remain the standard immunosuppression regimen post-transplant. Although tacrolimus is used as the primary CNI, target therapeutic levels vary across recipients due to adverse effects and tolerability, sometimes requiring switching over to Cyclosporine. We hypothesized that ACR within the first year is associated with switching CNI from Tacrolimus to Cyclosporine. Methods We performed a cross-sectional study of 255 adult lung transplant recipients between June 2019 to November 2024 at Mayo Clinic, Florida. Demographics, induction regimens, CNI type and their levels (average low and high levels) were compared between the 2 groups. The institutional maintenance immunosuppression regimen is Tacrolimus, Mycophenolate Mofetil (MMF) and prednisone, but could be switched to Cyclosporine if the previous regimen is not tolerated. The primary outcome was ACR <1 year diagnosed based on biopsy and/or clinical criteria. Comparisons between groups were performed using Chi-Square test for categorical variables and t-test or Wilcoxon Rank sum test for continuous variables. Multivariable regression analysis was performed with ACR <1 year as the outcome to adjust for the confounders. Results Our cohort included 255 lung transplant recipients with median age of 63 years, 61% Male, 84% Caucasians, 88% bilateral lung transplant (Further details elucidated in Table 1). A total of 173 (67%) out of 255 patients had ACR <1 year. The group with ACR < 1 year had higher proportion of Interstitial Lung Disease (ILD) (81% vs 68%, p = 0.044), use of Basiliximab for induction (70% vs 55%, p = 0.018), and cyclosporine instead of tacrolimus (23% vs 11%, p = 0.027). Group with ACR <1 year also had higher Antibody Mediated Rejection (AMR) < 1year (15% vs 6.1%, p = 0.041) and higher CLAD (BOS 0p-3: 43% vs 25.6%, p = 0.033) compared to the group without ACR < 1 year (Table 1.1). Multivariate regression analysis showed ILD (adjusted odds ratio, aOR 2.84, 95% CI 1.31 - 6.27, p = 0.008) and use of cyclosporine (aOR 2.55, 95% CI 1.07 - 6.78, p = 0.034) as independent predictors of ACR < 1 year (Table 2). Conclusions The presence of ACR < 1 year was associated with the use of Cyclosporine over Tacrolimus as a maintenance regimen. Also, ACR < 1year was associated with higher AMR and CLAD. Further prospective studies are needed to study this long-term given its significant prognostic implications. This abstract is funded by: Not Applicable

Abstract Rationale Fungal infections remain a major cause of morbidity and mortality post lung transplant due to unique exposure of the allograft to the external environment and the intensity of immunosuppression. Single-center studies have described variable rates of fungal infections. Contemporary population-level data with temporal trends, pathogen distribution, and associated outcomes are limited. Leveraging a large multicenter real-world dataset, we aimed to characterize incidence, prevalence and clinical outcomes of fungal infections among adult lung-transplant recipients. Methods Data were obtained from the TriNetX Global Collaborative Network (160 HCOs). Adult lung-transplant recipients (≥18 years) were identified between 2005 and 2024, using ICD and CPT procedure codes. Patients with solid organ transplants other than lung, combined-organ transplant or stem-cell transplant and HIV patients were excluded. Patients with pre transplant fungal infections were also excluded. Pre-transplant characteristics included demographics, comorbidities within a year, laboratory values within seven days, and medication within 90 days before transplantation. Post-transplant fungal infections were identified using ICD-10 codes for Aspergillus, Candida, Cryptococcus, Mucorales, Histoplasma, Blastomyces, Coccidioides, and Pneumocystis. TriNetX platform was utilized for statistical analysis. Incidence and prevalence of infections, all-cause mortality and transplant rejection were analyzed. Results A total of 12,857 adult lung-transplant recipients were identified. The mean age at transplantation was 57.6 ± 13.4 years, with a male predominance of (57%) and majority were white (65%). Average BMI was 26.8 ± 5.7 kg/m². The most common pulmonary conditions were COPD (15%), pulmonary fibrosis (17%), pulmonary hypertension (9%), bronchiectasis (3%), and cystic fibrosis (3%). Pre-transplant fungal and viral screening assays were rarely available (<1%). Medication exposure within 90 days prior to transplant demonstrated prednisone prescription (17%) methylprednisolone (7%), tacrolimus (6%), and mycophenolate mofetil (7%). Azathioprine and basiliximab were used in 2% each. Systemic antifungals (voriconazole, posaconazole, or fluconazole) in approximately 1% each.The overall incidence of post-transplant fungal infection was 3 % across full study period, rising to 7% in the modern era (2015-2024). Most frequently identified pathogens were Candida spp. (4.8%) and Aspergillus spp. (2.9%), followed by Pneumocystis Jirovecii (0.5%). Infection rates increased from 22 per 1,000 (2005-2014) to 75 per 1,000 (2015-2024) suggestive of improved diagnostic sensitivity and data capture, and longer post-transplant survival. All-cause mortality 5-year post transplant was 22.1%, and rejection rate was 22.5%. Conclusion Our study highlights a rising burden of fungal infections among lung-transplant recipients with potential implications for early post-transplant surveillance and antifungal prophylaxis strategies. This abstract is funded by: None

Abstract Rationale Fungal infections are common after lung transplantation and may adversely affect graft function and survival, but long-term outcomes remain incompletely defined. Using a large multicenter real-world dataset, we aimed to study the impact of post-transplant fungal infections on clinical outcomes of lung transplant recipients. Methods We conducted a retrospective, cohort study using the TriNetX Global Collaborative Network, which aggregates de-identified electronic health records from >160 healthcare organizations across North America, Europe, and Asia. Adult lung transplant recipients (≥18 years) between 2005 and 2024 were identified using ICD-10 and CPT codes. Patients with post-transplant fungal infection (aspergillosis, candidiasis, mucormycosis, histoplasmosis, coccidioidomycosis, blastomycosis) and matched controls without fungal infection within one year before or any time after transplant were identified. The index date was the date of transplantation. Propensity-score matching was performed on demographics, comorbidities, laboratory values, procedures and immunosuppressive medications. Outcomes included all-cause mortality (primary), allograft rejection, and chronic lung allograft dysfunction (CLAD) at 6 months, 1 year, 3 years, and 5 years. Kaplan-Meier and Cox proportional hazards models were used to estimate risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs). Analyses were conducted in TriNetX Analytics (v25.0, Cambridge, MA). Results A total of 3,083 patients with post-transplant fungal infection and 11,625 patients without infection were identified. Mean age was 58 ± 13 years, and 56% were male. The most common pulmonary comorbidities were chronic obstructive pulmonary disease, unspecified pulmonary fibrosis, idiopathic pulmonary fibrosis and bronchiectasis. Immunosuppression exposure was similar across groups. After propensity score matching across 56 clinical variables, both groups (1,790 per group) were well balanced. Mortality was higher in the fungal infection cohort at all follow-up points: 13.% vs 9% at 6 months (RR 1.45, 95% CI 1.2-1.75, p = 0.001), 17.8% vs 13% at 1 year (RR 1.36, p = 0.0001), 27.7% vs 21% at 3 years (RR 1.28, p < 0.0001), and 33 % vs 25% at 5 years (RR 1.32, p < 0.0001). Allograft rejection remained consistently higher (46-61% vs 22-34%), while CLAD occurred two- to three-fold more frequently (1.8-5.7% vs 0.7-2%). Conclusion Post-transplant fungal infection is independently associated with significantly increased mortality, acute rejection, and CLAD following lung transplantation. These findings underscore the need for early fungal surveillance, optimized antifungal prophylaxis, and individualized immunosuppression strategies to improve long-term patient outcomes. This abstract is funded by: None

Abstract Background Lung transplantation remains the accepted treatment modality of choice for life-threatening advanced lung disease due to established benefits of improving survival and functional status of the patients. However, the annual mortality of lung waitlist candidates remains high, reflecting ongoing donor-recipient mismatches and prolonged wait times. Modalities such as extracorporeal membrane oxygenation (ECMO) have been effectively used as a “bridge to transplant” (BTT) in high-risk patients on waitlist. Objective To evaluate trends in ECMO utilization, waitlist dynamics, and outcomes among lung transplant candidates between 2018 and 2024, with emphasis on the use of ECMO as a bridge to transplantation. Methods We conducted a retrospective chart review of all ECMO runs performed between 2018 to 2024 at the Mayo Clinic Florida Hospital. Among these, patients who underwent evaluation for lung transplantation were identified, and their waitlisting patterns, transplant outcomes, and peri-transplant ECMO status were described. Results Between 2018 and 2024, a total of 348 ECMO runs were recorded among 293 patients. Annual ECMO runs increased steadily from 17 in 2018 to 83 in 2024 (2019: 33, 2020: 30, 2021: 61, 2022: 56, 2023: 68, 2024: 83). Out of these patients, 142 underwent evaluation for lung transplantation and 133 (93.67%) were placed on the waitlist. Among waitlisted patients, 105 (78.9%) were listed before ECMO initiation, 23 (17.3%) during ECMO, and 5 (3.8%) after decannulation. Waitlist outcomes included 116 (87.2%) transplanted, 16 (12.0%) deaths before transplant, and 1 (0.8%) clinical improvement precluding transplant. Among 116 transplanted patients, 36 patients (31.03%) received ECMO as a bridge to lung transplantation. The annual patients bridged with ECMO demonstrated a progressive rise: 1 (2019), 3 (2020), 9 (2021), 6 (2022), 9 (2023), and 8 (2024). Among these 36 patients, 29 (80.56%) remained on ECMO support in the immediate post-transplant period. At the latest follow-up, mortality among BTT recipients was 9 (25%). Conclusion ECMO utilization has expanded substantially over the past several years reflecting its expanding role in supporting critically ill patients. There has been increased utilization of ECMO as a bridge to lung transplantation in order to support high risk candidates awaiting donor organs. The post-transplant mortality among BTT recipients was 25%, which highlights the importance of peri-transplant management to optimize long-term outcomes in this high-risk cohort. This abstract is funded by: None

Abstract Introduction Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of surfactant-derived lipoproteinaceous material within the alveoli, resulting in impaired gas exchange. While most cases are autoimmune, caused by anti-GM-CSF antibodies, secondary PAP results from macrophage dysfunction due to malignancy, infection, or inhalational toxins. E-cigarette or vaping product use-associated lung injury (EVALI) is an emerging clinical entity, but its potential to trigger secondary PAP remains poorly defined. We report a unique, treatment resistant case of vaping-induced secondary PAP, expanding the clinical spectrum of EVALI. Description A 28-year-old male with a 9-year history of daily nicotine vaping and frequent cannabis wax inhalation presented with progressive exertional dyspnea, hypoxemia, and digital clubbing. Chest CT showed diffuse ground-glass opacities and interlobular septal thickening, characteristic of the classic “crazy paving” pattern. BAL revealed PAS-positive lipoproteinaceous material, and lung biopsy confirmed intra-alveolar surfactant accumulation and foamy macrophages, consistent with PAP. Negative anti-GM-CSF antibodies excluded autoimmune PAP. Despite vaping cessation and aggressive management, including 5 months of systemic corticosteroids, a 7-day trial of inhaled GM-CSF (sargramostim), and empiric antibiotics, his condition progressed to respiratory failure requiring high-flow oxygen (FiO2 70%). Whole-lung lavage was deferred due to refractory hypoxemia. Ultimately, he underwent bilateral lung transplantation, highlighting the profound severity and irreversible nature of the disease. Discussion This case underscores an urgent public health concern as vaping use surges among young adults. Chronic inhalation of nicotine and cannabis aerosols may result in irreversible alveolar macrophage dysfunction, culminating in secondary PAP. The patient’s lack of response to standard therapies and progression to end-stage respiratory failure emphasizes the seriousness of vaping-related lung injury. Clinicians should maintain a high index of suspicion for PAP in young patients with unexplained respiratory symptoms and a history of vaping. Public health efforts must prioritize regulation and education to reduce vaping-related lung disease. This abstract is funded by: None

Abstract Introduction Interstitial lung disease-associated pulmonary hypertension (ILD-PH) is a clinically challenging entity that lies on a pathophysiologic spectrum between pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We compared the metabolomes of patients with ILD-PH to those with PAH and ILD to characterize the PAH-ILD axis and determine whether ILD-PH patients can be phenotyped based on their metabolomic similarity to PAH. Methods Using untargeted metabolomics profiles from patients with PAH, ILD, and ILD-PH in the large, U.S.-based, NIH-funded, multi-center PVDOMICS cohort, we trained an anchor-based classifier on PAH and ILD metabolomes using supervised PLS-DA with a 75/25 train/test split. Primary and secondary PH or risk-group classifications in PVDOMICS were based on expert adjudication of clinical data including right heart catheterization hemodynamics, pulmonary function testing, chest imaging, and laboratory results. We then applied the trained model to each ILD-PH patient to assign a PAH similarity score. We classified patients as having a PAH-like or ILD-like metabolomic phenotype using an optimal PAH similarity score cutoff of 0.5 then compared PAH metabolomic similarity to expert-adjudicated primary and secondary WSPH classifications in PVDOMICS. We implemented FELLA, a network-based metabolomics enrichment method, to holistically characterize the biologic underpinnings of PAH, ILD-PH, and ILD metabolomes. Results We analyzed 244 patients with PAH, 54 with ILD, and 47 with ILD-PH. The anchor-based classifier demonstrated high train-test performance with a c-statistic of 0.81 and 78% agreement with expert-adjudicated diagnoses. Among the ILD-PH patients, 23 were classified as PAH-like and 24 as ILD-like (74% agreement with expert adjudication, Cohen’s kappa 0.49, Hedge’s g estimate of 0.86). FELLA enrichment revealed core glycolytic and bioenergetic pathways were enriched in both pure PAH and ILD-PH. Comparison of diffusion Z-scores between groups demonstrated subtle but biologically coherent differences in several reaction-level nodes, including lactate, NADPH oxidoreductase, and phosphofructokinase, which were enriched in ILD-PH. Conclusion Patients with ILD-PH demonstrate clinically relevant metabolomic phenotypes. Examination of the network biology underlying ILD-PH may point to potential therapeutic targets in this vulnerable subgroup with lagging clinical outcomes. This abstract is funded by: Pulmonary Fibrosis Foundation PFF Scholars Program