Outcomes In Lung Transplant Recipients Research Articles

Impact of Prolonged Cold Ischemia Time on Long-Term Survival in Lung Transplant Recipients

Cold ischemia time (CIT) influences short- and long-term outcomes in lung transplant recipients. Most studies proved that prolonged CIT causes increased mortality. This study aimed to investigate the impact of prolonged CIT on patient survival time after lung transplantation (LTx). The retrospective study group consisted of 139 patients who underwent double LTx in a single center between January 2018 and August 2022. Prolonged ischemic time (PIT) was defined as total ischemic time >6 hours and divided into smaller time intervals according to increasing PIT (6-8, 8-10, 10-12, >12 hours). The assessed outcomes were 1- and 4-year survival. Among the study group, PIT was observed in 98% (n = 137), and its average value was 10.33 hours. The prolonged CIT of 6 to 8 hours occurred in 10% (n = 14), 8 to 10 hours in 34% (n = 47), 10 to 12 hours in 36% (n = 49), and >12 hours in 20% (n = 27). In a comparison of 1-year survival between the PIT 6- to 10-hour group and the >10-hour arm (88% vs 78%), the difference was not statistically significant (P > .05). PIT is a risk factor for reduced long-term survival in LTx recipients. Increasing PIT may be associated with higher mortality at 1 and 4 years. All efforts to reduce the duration of ischemic time can benefit patient survival after LTx.

Lung transplantation following prior cardiac surgical procedures

IntroductionAs lung transplant candidates are older with increased comorbidities, we sought to examine the prevalence and outcomes of lung transplant recipients after prior cardiac surgery. MethodsLung transplants were identified from the United Network for Organ Sharing/Organ Procurement and Transplantation Network Database. Patients were stratified based on prior cardiac surgery (No Surgery [NS], Prior coronary artery bypass grafting [CABG], Prior Valve [Valve]). Unadjusted comparisons were performed amongst all groups, and propensity matching was utilized for adjusted comparisons. Survival was examined with Kaplan-Meier methods. Results28,710 patients were identified, 467 (1.6%) had prior CABG and 84 (0.3%) had prior valvular surgery. Prior to matching, the NS group was significantly younger, less commonly male, and had lower lung allocation scores. There were significantly fewer bilateral lung transplants in the CABG and Valve groups. Length of stay was shortest in the CABG group, but there were no significant differences in postoperative stroke, dialysis, or in-hospital mortality. There was an increased incidence of cardiac/cerebrovascular cause of death in CABG recipients (18.3%) and malignancy death in Valve recipients (23.3%). Following matching, CABG 5-year survival was lower than NS (p<0.01), while there was no significant difference between NS and Valve groups (p=0.4). ConclusionsCABG and Valve recipients had decreased survival, however not at levels prohibitive to transplantation. Due to potentially increased risk of cardiovascular mortality, providers should evaluate the burden of vascular disease in potential recipients with prior CABG to improve patient selection and maximize post-transplant survival.

(1045) - Title: Clinical Outcomes of Lung Transplant Recipients with Myelodysplastic Syndrome and Short Telomere Syndrome

(1045) - Title: Clinical Outcomes of Lung Transplant Recipients with Myelodysplastic Syndrome and Short Telomere Syndrome

(1011) - Mortality and Lung Allograft Outcomes in Lung Transplant Recipients with Post-Transplant COVID-19 Infection

(1011) - Mortality and Lung Allograft Outcomes in Lung Transplant Recipients with Post-Transplant COVID-19 Infection

Nanoparticle targeting of neutrophil glycolysis prevents lung ischemia-reperfusion injury

Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils. NP-Ly6G(2-DG)–treated neutrophils were unable to adapt to hypoglycemic conditions of the lung airspace environment as evident by the loss of demand-induced glycolysis, reductions in glycogen and ATP content, and an increased vulnerability to apoptosis. NP-Ly6G(2-DG) treatment inhibited pulmonary IRI following hilar occlusion and orthotopic lung transplantation. IRI protection was associated with less airspace neutrophil extracellular trap generation, reduced intragraft neutrophilia, and enhanced alveolar macrophage efferocytotic clearance of neutrophils. Collectively, our data show that pharmacologically targeting glycolysis in neutrophils inhibits their activation and survival leading to reduced pulmonary IRI.

COVID-19 infection is mild and has minimal impact on lung function in well vaccinated and widely treated lung transplant recipients

BackgroundCOVID-19 has become a common infection affecting lung transplant recipients (LTR), who are at high risk for poor outcomes. Outcomes early in the pandemic were poor, but since the rollout of vaccination and novel COVID-19 treatments, outcomes of LTR have not been well described. Our aim was to evaluate the effect of COVID-19 on the clinical course and lung function trajectory in an Australian cohort of LTR. MethodsData was retrospectively collected from LTR with confirmed COVID-19 managed at Alfred Health, between August 2020 and December 2022. Baseline demographics, COVID-19 disease details (including severity) and spirometry pre and post infection have been analysed. ResultsA total of 279 LTR were included. The cohort was comorbid, but well vaccinated, with 275/279 (98.6%) having >2 COVID-19 vaccines at symptom onset. Severe disease occurred in only 17 cases (6%) and overall mortality was very low (4%). Prompt treatment with antivirals, particularly remdesevir (OR 0.18, 95% CI 0.04-0.81, p=0.02] and vaccination (OR 0.24, CI 0.08-0.81, p=0.01] were protective. There was not a clinically significant drop in lung function post COVID-19 with the median absolute decline in forced expiratory volume (FEV1) being 40mL (IQR 5-120mL, p<0.001), with a decline of >10% occurring in only 42 patients (17%). After multivariate adjustment, only rejection prior to COVID-19 was significantly associated with FEV1 decline afterwards (OR 3.74, 1.12-11.86, p=0.03). ConclusionsIn our highly COVID-19 vaccinated, promptly treated LTR, the majority of COVID-19 infections were mild and did not result in a clinically significant decline in lung function.

COVID-19 Outcomes in Lung Transplant Recipients Following Pre-Exposure Prophylaxis With Tixagevimab-Cilgavimab During the Omicron BA.5 Surge: A Single Center Analysis.

Lung transplant (LTx) recipients are at high risk for COVID-19 related morbidity and mortality. Data regarding pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab in this population are scarce. We therefore evaluated COVID-19 breakthrough infections and COVID-19 related complications after PrEP in a retrospective single-center study, including 264 LTx recipients who received PrEP between June 2022 and December 2022, when Omicron BA.5 was the dominant circulating SARS-CoV-2 variant. PrEP was indicated for fully vaccinated patients with poor seroconversion (anti-S <260BAU/mL). COVID-19 breakthrough infection after PrEP occurred in 11.0% within the first 3months, increasing to 17.4% within 6months. Hospitalization rate rose from 27.6% to 52.9% (p = 0.046), while ICU admissions and COVID-19 mortality remained low, respectively occurring in 6.5% and 4.3% of patients with breakthrough infection within 6months. COVID-19 breakthrough infection and associated hospitalization remained an important problem during the Omicron BA.5 surge in fully vaccinated LTx recipients with deficient seroconversion, despite PrEP with tixagevimab-cilgavimab. However, ICU admissions and COVID-19 mortality were low. Waning of neutralizing effects of PrEP and changing circulating SARS-CoV-2 variants may explain increases in COVID-19 infections and hospitalizations over time after PrEP, highlighting the need for novel, long-term effective PrEP strategies in these high-risk patients.

Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction

BackgroundAspiration is a known risk-factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration – however they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs while others, like pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. MethodsExpression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to pre-existing markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after anti-reflux surgery was assessed in a third cohort of LTRs. ResultsPGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Anti-reflux surgery was associated with reduced airway PGA4. ConclusionsAirway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Immune outcomes of lung transplant recipients with different cytochrome P450 3A5 phenotypes after discontinuation of voriconazole antifungal prophylaxis.

Tacrolimus forms the backbone of immunosuppression regimens in lung transplant recipients (LTRs). It is extensively metabolized by cytochrome P450 (CYP) 3A5 enzymes, of which polymorphisms can significantly affect tacrolimus dose requirements. It is unknown how coadministration of tacrolimus with voriconazole, a potent CYP3A5 inhibitor, affects rejection rates or empiric dose adjustments needed after voriconazole discontinuation. This retrospective cohort study compares LTRs with poor (PR) versus intermediate/extensive (IE) CYP3A5 metabolizer phenotypes. The primary endpoint is cumulative immune outcomes within three months of voriconazole discontinuation; secondary endpoints include change in tacrolimus dose-to-concentration ratios after voriconazole discontinuation. Thirty-four patients underwent full analysis: 13 IE and 21 PR metabolizers. A higher proportion of IE metabolizers were African American (46.2%vs. 9.5%, p=.03). There was no significant difference in composite immune outcomes, though there was a proportionally higher frequency of new donor-specific antibody development in PR metabolizers (14.3%vs 7.7%, p=.56). Both groups required approximately 2.5 to 3-fold tacrolimus dose increases post-voriconazole discontinuation to re-attain therapeutic levels. This novel investigation sheds light on how CYP3A5 phenotype could be used to guide tacrolimus dosing, with the goal of preventing both toxicity and organ rejection.

Chronic lung allograft dysfunction is associated with an increased number of non-HLA antibodies

BackgroundChronic Lung Allograft Dysfunction (CLAD) is the major cause of adverse outcomes in lung transplant recipients. Multiple factors, such as infection, alloimmunity, and autoimmunity, may lead to CLAD. Here, we aim to examine the role of non-HLA antibodies in CLAD in a large retrospective cohort. MethodsWe analyzed non-HLA antibodies in the pre-and post-transplant sera of 226 (100 CLAD, 126 stable) lung transplant recipients from 5 centers, and we used a separate cohort to confirm our findings. ResultsA panel of 18 non-HLA antibodies was selected for analysis based on their significantly higher positive rates in CLAD vs. stable groups. The panel-18 non-HLA antibodies (n>3) may be positive pre- or post-transplant; the risk for CLAD is higher in the latter. The presence of both non-HLA antibody and HLA donor-specific antibody (DSA) was associated with an augmented risk of CLAD (HR=25.09 [5.52–14.04], p <0.001), which was higher than that for single-positive patients. In the independent confirmatory cohort of 61 (20 CLAD, 41 stable) lung transplant recipients, the risk for CLAD remained elevated in double-positive patients (HR=10.67 [0.98–115.68], p=0.052). After adjusting for non-standard immunosuppression, patients with double-positive DSA/Non-HLA antibodies had an elevated risk for graft loss (HR=2.53 [1.29–4.96], p=0.007). ConclusionsCirculating non-HLA antibodies (n>3) were independently associated with a higher risk for CLAD. Furthermore, when non-HLA antibodies and DSA were detected concomitantly, the risk for CLAD and graft loss was significantly increased. These results show that humoral immunity to HLA and non-HLA antigens may contribute to CLAD development.

2714. Invasive Fungal Disease in Lung Transplant Recipients: Incidence, Risk Factors, and Outcomes

Abstract Background Invasive fungal disease (IFD) is common after lung transplant and is associated with increased morbidity and mortality. Antifungal prophylaxis is a common preventative strategy against IFD in lung transplant recipients (LTRs). We assessed the incidence of IFD in the first 3-years post-transplant, diagnosed by EORTC/MSG criteria, risk factors for developing IFD, and outcomes of LTRs stratified by development of IFD at a single center that does not use universal antifungal prophylaxis post-lung transplant. Table 1 Preoperative and perioperative characteristics and clinical outcomes of lung transplant recipients stratified by invasive fungal disease (IFD) status Methods A single-center, retrospective study of lung transplant recipients between January 2017 and December 2019 was performed with 3-year follow-up. Donor and recipient preoperative characteristics, microbiologic and radiographic data, perioperative characteristics, and 1- and 3-year outcomes were adjudicated and analyzed. Results In this 3-year study period, 168 patients underwent lung transplant. 26 (15%) developed IFD; 23 (14%) were proven or probable, and 3 (1%) were possible [Table 1]. 21 (81%) had evidence of pulmonary infection and 17 (65%) were mold infections with Aspergillus being the predominant pathogen. 4 (15%) were Candida. 81% (21/26) of patients who developed IFD were recipients of bilateral lung transplants compared to 95% (135/142) of patients who did not develop IFD (p = 0.022). Other donor/recipient characteristics and 12-month outcomes between patients who did vs did not develop IFD were similar. 21% of patients (4/19) who developed IFD had developed antibody-mediated rejection (AMR) by three years post-transplant compared to only 4% of patients without IFD (5/112) (p = 0.025). The incidence of acute cellular rejection, chronic allograft rejection, and overall survival at three years were similar. Conclusion Despite the lack of universal antifungal prophylaxis in the first 90 days post-transplant, we observed a low incidence of IFD in LTRs at our center in this 3-year cohort. Other than receipt of a single vs bilateral lung transplant, there were no significant differences in preoperative or perioperative recipient characteristics. Other than an increased proportion of patients who had AMR, patients who developed IFD had similar overall outcomes to those who did not have IFD, including overall survival at 1, 2, and 3 years. Disclosures Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Astellas: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Fujifilm: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support

2732. Peri-Operative Antibiotic Management for Lung Transplant Recipients with Cystic Fibrosis

Abstract Background Lung transplant (LTx) recipients universally receive peri- and post-transplant antibiotics. Approaches to antibiotics for candidates with cystic fibrosis (CF) are institution specific. Little has been published about these practices. Routine LTx perioperative prophylaxis at our institution is 96 hours of vancomycin and cefepime with antibiotics then adjusted for positive intraoperative donor and recipient cultures. In recipients with CF, perioperative prophylaxis is determined pre-LTx to cover colonizing organisms isolated in culture from the 2 years before LTx, adjusted for intraoperative cultures, and administered for 14-21 days post-LTx. Our study aims to add to the current literature by describing our center’s experience with antibiotic management and outcomes in lung transplant recipients with CF to help guide best practices for prophylaxis strategies for this patient population. Methods We performed a retrospective chart review of patients with CF who underwent LTx from 3/1/2015-11/18/21 at our center and were colonized pre-LTx with MRSA, Pseudomonas aeruginosa, or Burkholderia cepacia complex. Peri- and post-operative antibiotic regimens, donor and recipient culture results, changes in antibiotic therapy post-LTx, and duration of antibiotic therapy were documented. Outcomes included rehospitalization, isolation in culture of the prophylaxis-targeted organisms post-LTx, and mortality, within 6 months of LTx. Results Nineteen incidents of LTx were included in this study. Pre-LTx colonizing organisms and antibiotics administered are outlined in table 1. Prophylaxis-targeted organisms were infrequently isolated in culture after LTx (table 2), with 7/19 (36.8%) developing post-transplant infection with prior colonizing organisms. Four (21.1%) recipients developed post-LTx Clostridioides difficile infection. One (5.3%) recipient died within 6 months post-LTx. Conclusion LTx recipients with CF who received targeted perioperative prophylaxis for pre-LTx colonizing organisms infrequently developed post-LTx culture positivity with the same bacteria including none during the antimicrobial prophylaxis period. Future prospective studies are needed to determine optimal antibiotic duration of peri-LTx antibiotics in this patient population. Disclosures All Authors: No reported disclosures

2728. Bronchial Cultures at Time of Transplant Affect Anastomotic Outcomes in Lung Transplant Recipients

Abstract Background Anastomotic complications after lung transplant cause significant morbidity and mortality. Estimates of complication prevalence in lung transplant recipients range from 5-20%. Many factors are hypothesized to contribute to airway complications, including the presence of bacteria and fungi at time of transplant. Our aim was to examine the contribution of airway cultures at the time of transplant to airway complications. Methods We performed a retrospective analysis of lung transplant recipients who developed bronchial complications at a single, tertiary care center between January 1, 2016 and March 31, 2020. We identified 68 cases with anastomotic complications during this time period, then compared this cohort to 131 cases without bronchial complications. Primary outcomes were airway complications at 30 and 90 days. Please refer to the attached tables for variables of interest. Results Of 199 total study participants, 68 (34%) were found to have airway complications. Overall, the most common bacterial isolate was Staphylococcus aureus (72 MSSA and 17 MRSA). The most common fungal isolate was Candida albicans (87). When examining the patients with airway complications, MRSA isolates at time of transplant showed a statistically significant increase in airway complications (p=0.03, OR=3). An increase in airway complications was not seen for patients with other positive bacterial or fungal cultures at 30 days or 90 days. Microbiological Risk Factors for Airway Complications Patient Demographics and Characteristics Conclusion MRSA isolates at time of transplant correlated to increased 30 day and 90 day bronchial complications. This study helps confirm the importance of monitoring airway cultures at the time of transplant. A multi-center study with a larger sample size may be needed to further delineate contributions of specific microorganisms, surgical techniques, as well as perioperative and prophylactic antimicrobials on bronchial complications. Disclosures Aaron D. Mishkin, MD, Pfizer: Grant/Research Support|Takeda: Advisor/Consultant

Acute Rejection of the Lung Allograft: Phenotypes and Management

Treatment options for end stage lung diseases are limited to stabilizing lung failure, decreasing disease progression, and symptom management, but significant reversal of lost lung function is often not possible. For well selected patients, lung transplantation may be a viable option to improve both longevity and quality of life. Though outcomes for lung transplant recipients have improved over several decades, long term survival still lags behind that of other solid organ transplant recipients. Longevity after lung transplantation is limited by chronic lung allograft dysfunction. Numerous insults to the allograft contribute to chronic rejection, alloimmune injuries including acute T-cell mediated and antibody mediated rejection are chief among them. Therefore, monitoring for and management of acute cellular and antibody mediated rejection are of paramount importance to those caring for lung transplant recipients. We provide an up to date and comprehensive review of acute rejection affecting lung allografts and attempt to highlight pathophysiology, risk factors, clinical presentation, rejection phenotypes, management strategies, as well as related from of acute allograft injury.

Lung Transplantation from hepatitis C+ donor lungs: Reassuring midterm outcomes

The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and mid-term outcomes of lung transplant recipients of HCV NAT+ donor allografts. All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity-score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by one year, early (30-day and in-hospital) mortality and both 1- and 3-year survival were compared between matched groups. A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%), and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, P<0.001), more often female (44% vs 39%, P<0.01) and more commonly died due to drug intoxication (56% vs 15%, P<0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, P=0.69) and female gender (43% vs 39%, P=0.15) but had lower lung allocation scores (38 vs 41, P<0.001) compared to others. Rates of acute rejection (13% vs 17%, P=0.09), early mortality (30-day: 2% vs 1%, P=0.59, in-hospital: 3% vs 4%, P=0.38) as well as 1- (90% vs 92%, P=0.29) and 3-year survival (69% vs 75%, P=0.13) were not significantly different between matched groups. Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.

Evolving impact of the COVID-19 pandemic on lung transplant recipients: A single-center experience

Lung transplant recipients (LTRs) are at increased risk of COVID-19-related morbidity and mortality; however, the disease severity has changed as SARS-CoV-2 variants have mutated. We compared COVID-19-related clinical outcomes in LTRs at different stages of the pandemic. We also identified risk factors for the development of severe COVID-19 independent of the dominant SARS-CoV-2 variant. This is a single-center, retrospective cohort study of LTRs with COVID-19. Cox regression analyses and bootstrapping were used to identify factors affecting COVID-19 severity. Between March 2020 and August 2022, 195 LTRs were diagnosed with COVID-19, almost half (89 [45.6%]) during the Omicron period. A total of 113 (58.5%) LTRs were hospitalized and 47 (24.1%) died. Age >65 years increased the risk of hospitalization and death. Although infection with the Omicron variant was associated with a lower risk of hospitalization, the median length of hospital stay (10 days, [IQR, 5- 19]) was similar between the variants. Intensive care unit (ICU) admission and death were more common with the Delta variant, but comparable between the original, Alpha, and Omicron variants. Remdesivir or molnupiravir reduced the risk of hospitalization, and monoclonal antibody therapy reduced the risk of ICU admission, intubation, and death. Vaccination and pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab did not significantly reduce COVID-19-related ICU admission, intubation, or mortality among LTRs. LTRs with COVID-19 continue to have high hospitalization rates and prolonged hospital stays, despite reduced virulence of the Omicron variant. More effective PrEP and therapeutic interventions for COVID-19 among vulnerable patient groups are needed.

Crossroads between Autoimmunity and COVID-19 in Lung Transplant Recipients.

The presence of a certain group of auto-antibodies (AAbs) is known to correlate with the severity of COVID-19. It is, however, unknown if such AAbs are prevalent and impact COVID-19-related outcomes in lung transplant recipients (LTRs) who are immunosuppressed. We performed a retrospective study of LTRs with COVID-19 and analyzed samples before and after COVID-19 for IgG AAbs. AAbs analysis was carried out using autoimmune and coronavirus microarray and the resulting cross-sectional differences in Ab-scores and clinical variables were analyzed using Fischer's Exact test for categorical variables and a paired t-test for continuous variables. Linear regression was used to analyze the differences in Ab-scores and COVID-19 severity. LTRs with non-severe [NS gp (n = 10)], and severe [S gp (n = 8)] COVID-19 disease were included. Ferritin and acute respiratory failure were higher in the S group (p = 0.03; p < 0.0001). Among the AAbs analyzed, interferon-related AAbs (IFN-alpha2, IFN-beta, IFN lamba, IFN-epsilon), eight interleukin-related AAbs, and several tissue-related AAbs were also found to be changed significantly from pre- to post-COVID-19 (p < 0.05). IFN-lambda (p = 0.03) and IL-22 (p = 0.002) were significantly associated with COVID-19 severity and remained significant in linear regression analysis while controlling for other variables. AAbs are common in LTRs, and certain groups of antibodies are particularly enhanced in LTRs with severe COVID-19. Preliminary observations of this study need to be confirmed by a larger sample size.

Effect of Mycetoma in Lung Transplant Patients – a Single Center Experience

Mycetomas are uncommon in lung transplant recipients. Prior studies have shown increased mortality associated with mycetoma in lung transplant recipients (LTR). We reviewed our center's experience in outcome of LTRs with pre -or post-transplant mycetoma. We retrospectively reviewed electronic health records of LTRs performed at our institute between January 1, 2013 to December 31, 2020. Mycetoma was present in less than 1 percent of LTR patients (7/1086). Mean age at the time of the transplant was 65 years. Idiopathic pulmonary fibrosis (5/7), interstitial lung disease (1/7), and sarcoidosis (1/7) were underlying pulmonary diagnoses. Seventy-one percent (5/7) received single lung transplant and 29% received double lung transplant. Seventy-one percent had negative serum galactomannan vs 29% (2/7) of patients who had positive serum galactomannan (one post and one pre). Fifty-seven percent had positive bronchoalveolar aspergillus galactomannan (23% had negative). A total of 42% (3/7) were found to have mycetoma before transplant and 58% (4/7) had mycetoma post transplant. Chest computed tomography findings in all patients were consistent with mycetoma. In our cohort of patients, mycetoma was not found to be the primary cause of death if diagnosed pre transplant. Transplant recipients with mycetoma pre transplant did not develop invasive fungal infection or mycetoma post transplant. Careful evaluation of lung transplant candidates with mycetoma is critical. Further studies are needed to determine optimal duration of antifungal therapy and to determine if surgical resection may be needed to manage post-lung transplant mycetoma.

Laparoscopic Toupet fundoplication: a safe and effective anti-reflux option in lung transplant recipients.

Fundoplication is known to improve allograft outcomes in lung transplant recipients by reducing retrograde aspiration secondary to gastroesophageal reflux disease, a modifiable risk factor for chronic allograft dysfunction. Laparoscopic Nissen fundoplication has historically been the anti-reflux procedure of choice, but the procedure is associated with discernable rates of postoperative dysphagia and gas-bloat syndrome. Laparoscopic Toupet fundoplication, an alternate anti-reflux surgery with lower rates of foregut complications in the general population, is the procedure of choice on our institution's lung transplant protocol. In this work, we evaluated the efficacy and safety of laparoscopic Toupet fundoplication in our lung transplant recipients. A prospective case series of 44 lung transplant recipients who underwent laparoscopic Toupet fundoplication by a single surgeon between September 2018 and November 2020 was performed. Preoperative and postoperative results from 24-h pH, esophageal manometry, gastric emptying, and pulmonary function studies were collected alongside severity of gastroesophageal reflux disease and other gastrointestinal symptoms. Median DeMeester score decreased from 25.9 to 5.4 after fundoplication (p < 0.0001), while percentage of time pH < 4 decreased from 7 to 1.1% (p < 0.0001). The severity of heartburn and regurgitation were also reduced (p < 0.0001 and p = 0.0029 respectively). Overall, pulmonary function, esophageal motility, gastric emptying, severity of bloating, and dysphagia were not significantly different post-fundoplication than pre-fundoplication. Patients with decreasing rates of FEV1 pre-fundoplication saw improvement in their rate of change of FEV1 post-fundoplication (p = 0.011). Median follow-up was 32.2months post-fundoplication. Laparoscopic Toupet fundoplication provides objective pathologic acid reflux control and symptomatic gastroesophageal reflux improvement in lung transplant recipients while preserving lung function and foregut motility. Thus, laparoscopic Toupet fundoplication is a safe and effective antireflux surgery alternative in lung transplant recipients.

Association of positive pre-transplant angiotensin II type 1 receptor antibodies with clinical outcomes in lung transplant recipients

IntroductionAutoantibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been previously associated with de novo donor-specific antibody (DSA) formation in lung transplantation. However, data regarding the clinical significance of AT1R-Ab in long-term graft function after lung transplantation are lacking. MethodsSeventy-one patients who underwent lung transplantation between July 2016 and January 2020 were enrolled in this study. We examined the relationship between pre-transplant AT1R-Ab levels and graft function, clinical outcomes, and human leukocyte antigen (HLA) DSA levels during the first 3 years post-transplantation. ResultsSeventeen (23.9%) patients were AT1R-Ab-positive, and 54 (76.1%) were AT1R-Ab-negative. The median antibody value of the AT1R-Ab-positive group was 18 [18–22.5] U/mL, while that of the AT1R-Ab-negative group was 5.1 [3.5–8.0] U/mL (p < 0.001). There was no significant difference in the median acute cellular rejection (ACR) scores between the two groups (median [interquartile range] 1 [0.8–3] vs. 0.7 [0–1]; p = 0.145). However, there was a significant difference in the distribution of the ACR scores between the two groups (p = 0.015). Most (41.2%) patients in the pre-transplant AT1R-positive group scored above 1. The incidence of de novo DSA was also higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (52.9% vs. 20.4%, p = 0.009). The incidence of chronic lung allograft dysfunction (CLAD) within 3 years was significantly higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (58.3% vs. 11.8%; p < 0.001). In the multivariate Cox regression analysis, AT1R-Ab positivity (hazard ratio, 9.46; 95% confidence interval, 2.89–30.94; p < 0.001) was significantly associated with early CLAD. Furthermore, Kaplan-Meier analysis showed that AT1R-Ab-positive patients had a shorter survival time (χ2 = 39.62, p < 0.001). ConclusionHigh AT1R-Ab levels in the pre-transplant serum of lung recipients were associated with the development of de novo HLA-DSA, ACR, early CLAD, and short survival.