Time Of Lung Transplantation Research Articles

Air Pollution Exposure at Time of Lung Transplant and Survival: Can We Do Better?

Air Pollution Exposure at Time of Lung Transplant and Survival: Can We Do Better?

Frequency of Unplanned Readmissions Following Lung Transplantation During the SAR-COV-2 Pandemic When Hospital Resources Were Strained

Despite the concerted efforts by lung transplant recipients (LTR) and their medical teams, hospital readmissions are common in the first year following transplantation. Reasons for unplanned readmissions include allograft rejection, infections, and respiratory failure before the SARS-COV-2 pandemic. Clinical predictors of readmissions have changed over time with the higher risk factors of acceptable criteria for recipients and donors. We aimed to assess more recent readmission rates based on group classifications to better understand specific groups that are at risk for various readmissions during the SARS-COV-2 pandemic when hospital resources were strained. A retrospective analysis for LTR at UCSD was performed from 1/1/2018 to 6/30/2022. We recorded the baseline demographics; LAS at the time of lung transplant; mechanical ventilation prior to lung transplant; the need for VV-or VA-ECMO prior to or after lung transplantation; categories for UNOS listing (groups A, B, C, D); PGD grade 3 based on the ISHLT definition; and acquisition of serious donor-derived infections. We recorded the primary reason for all the readmissions and the duration of admission. Descriptive statistics were used for the analysis of this 4.5-year patient cohort. 149 LT were performed. 29 were single LTR while 120 were bilateral LTR. Median age of 57 years, 63 patients (42%) were female. Indications for transplantation included 28 (19%) group A, 19 (13%) group B, 12 (8%) group C, and 90 (60%) group D. The median length of follow-up following lung transplant was 1.7 years. Collectively, there were 73 patients (49%) that required readmissions. On average, there are 2.5 readmissions per patient for our cohort. Most common reasons for unplanned readmission included infections, transplant-related (transplant rejection, other complications of transplant, etc.), and GI Related. This was primarily seen in the group D cohort. The median hospital LOS at readmission was 3.8 days (4 hours to 34.6 days). Despite infection being the leading cause of readmission, only 11 cases were related to COVID-19 infection. No death occurred with a readmission. Groups B and D appear to be at a higher risk for readmission, irrespective of the pre-LT LAS and need for mech vent or VV-ECMO.

Clinical impact of pre-existing acute exacerbation in patients with interstitial lung disease who underwent lung transplantation

BackgroundAcute exacerbation of interstitial lung disease (AE-ILD) significantly impacts prognosis, leading to high mortality rates. Although lung transplantation is a life-saving treatment for selected patients with ILD, its outcomes in those presenting with AE-ILD have yielded conflicting results compared with those with stable ILD. This study aims to investigate the impact of pre-existing AE on the prognosis of ILD patients who underwent lung transplantation.MethodWe conducted a single-center retrospective study by reviewing the medical records of 108 patients who underwent lung transplantation for predisposing ILD at Asan Medical Center, Seoul, South Korea, between 2008 and 2022. The primary objective was to compare the survival of patients with AE-ILD at the time of transplantation with those without AE-ILD.ResultsAmong the 108 patients, 52 (48.1%) experienced AE-ILD at the time of lung transplantation, and 81 (75.0%) required pre-transplant mechanical ventilation. Although the type of ILD (IPF vs. non-IPF ILD) did not affect clinical outcomes after transplantation, AE-ILD was associated with worse survival outcomes. The survival probabilities at 90 days, 1 year, and 3 years post-transplant for patients with AE-ILD were 86.5%, 73.1%, and 60.1%, respectively, while those for patients without AE-ILD were higher, at 92.9%, 83.9%, and 79.6% (p = 0.032). In the multivariable analysis, pre-existing AE was an independent prognostic factor for mortality in ILD patients who underwent lung transplantation.ConclusionsAlthough lung transplantation remains an effective treatment option for ILD patients with pre-existing AE, careful consideration is needed, especially in patients requiring pre-transplant mechanical respiratory support.

Provider beliefs and practices regarding the management of obesity in lung transplant recipients

Obesity at the time of lung transplant is associated with decreased survival. How providers manage obesity after lung transplantation is unknown. We performed an international survey of lung transplant providers to assess beliefs and practices regarding post-transplant obesity management. Eighty-one providers initiated the survey and 73 (90%) completed the full survey. Respondents were primarily North American-based pulmonary physicians. Nearly all providers believe treating obesity improves quality of life (99%) and survival (95%) after lung transplantation, but that only 41% of patients attempting weight loss are successful. While respondents nearly always recommend diet (96%), exercise (92%), and dietician consultation (89%), they less frequently recommend prescription weight loss medications (29%) or bariatric surgery (11%). Lung transplant providers are motivated to treat obesity in transplant recipients. However, there is a gap between general obesity treatment guidelines and lung transplant practice. Additional training, education, and trials in this population could address this gap.

Extracorporeal membrane oxygenation bridge to pediatric lung transplantation: Modern era analysis.

Survival outcomes of children on extracorporeal membrane oxygenation (ECMO) at time of lung transplant (LTx) remain unclear. Pediatric first-time LTx recipients transplanted between January 2000 and December 2020 were identified in the United Network for Organ Sharing Registry to compare post-transplant survival according to ECMO support at time of transplant. For a comprehensive analysis of the data, univariate analysis, multivariable Cox regression, and propensity score matching were performed. During the study period, 954 children under 18 years of age underwent LTx with 40 patients on ECMO. We did not identify a post-LTx survival difference between patients receiving ECMO when compared to those that did not. A multivariable Cox regression model (Hazard ratio = 0.83; 95% confidence interval: 0.47, 1.45; p = .51) did not demonstrate an increased risk for death post-LTx. Lastly, a propensity score matching analysis, retaining 33 ECMO and 33 non-ECMO patients, further confirmed no post-LTx survival difference comparing ECMO to no ECMO cohorts (Hazard ratio = 0.98; 95% confidence interval: 0.48, 2.00; p = .96). In this contemporary cohort of children, the use of ECMO at the time of LTx did not negatively impact post-transplant survival.

Benefit of Kidney Transplantation for Post Lung Transplantation Renal Failure

IntroductionNephrotoxicity is a significant side effect of thoracic transplantation. Many lung transplant patients will require subsequent renal transplantation (KAL). Recently, simultaneous lung/kidney transplants (SLuK) have become an attractive option for patients with end-stage renal disease at the time of lung transplantation. This article explores SLuK outcomes compared to conventional KAL, as well as outcomes among KAL patients against those were KAL listed but never transplanted. Materials and methodsThe United Network for Organ Sharing/the Organ Procurement and Transportation Network database was used to identify SLuK patients (n = 74), KAL transplants (n = 456), and patients who were listed for KAL but were never transplanted (n = 626). Significance was determined by chi2, Wilcoxon rank sum test, or independent t-tests. Death-censored graft survival for subgroups was estimated using Kaplan–Meier with log-rank for significance. Analyses were completed using SPSS Statistics 28. ResultsThe SLuK cohort was older (P = 0.04), more likely diabetic (P < 0.001), and had shorter life expectancies (P < 0.001) than KAL patients. Of those SLuK transplants within 5 y, 84% of patients were alive 1 y post transplant and 82% were alive 3 y post-transplant (compared to 74.6% and 60.3% of overall SLuK). Patients who did undergo KAL were younger and had a lower body mass index (both P < 0.001) compared to those who did not. Those who received a kidney had increased survival times compared to WL patients (P < 0.001). ConclusionsConventional KAL transplants are still favorable for average lung recipients. However, recent improvements have made SLuK an option for patients with renal dysfunction. Those patients who were able to receive KAL transplants were better surgical candidates than those who remained on the waitlist.

Microbiological and Clinical Outcomes of Methicillin-Susceptible Staphylococcus aureus Isolated in Lung Transplant Perioperative Donor and Recipient Respiratory Cultures

Staphylococcus aureus is one of the most common organisms isolated from respiratory secretions in lung transplant donors and recipients perioperatively. Within the first 90 days after lung transplantation, methicillin-susceptible Staphylococcus aureus (MSSA) infections have been associated with increased mortality and acute and chronic rejection. However, it is unclear whether respiratory cultures positive for MSSA at the time of transplantation can lead to clinically significant infection. The aim of this study was to assess the microbiological and clinical outcomes for lung transplant recipients (LTRs) with positive perioperative donor or/and recipient respiratory cultures for MSSA. A retrospective study was conducted evaluating MSSA-positive respiratory cultures at the time of lung transplantation from donors and/or recipients from January 1, 2008, to December 30, 2019. Patients who did not have a bronchoalveolar lavage at 2 weeks after the lung transplant or died within 2 weeks of lung transplant were excluded. The main outcome was MSSA eradication at 2-week bronchoscopy. Recipients were evaluated for MSSA infections at the 12-week period after the transplant. Of the 1,678 individuals who underwent lung transplantation, 218 LTRs had S. aureus isolated in perioperative donor or recipient respiratory cultures, and 29 were subsequently excluded. Of the remaining 189 LTRs, MSSA eradication at the 2-week bronchoscopy was achieved in 186 (98.4%) recipients. During the 12-week follow-up, 15 (7.9%) recipients were diagnosed with MSSA pneumonia; concurrent MSSA bacteremia was noted in one recipient. No anastomotic infection, empyema, or lung abscess related to MSSA was diagnosed during the follow-up period. In LTRs, the rate of MSSA eradication at 2-week post-transplant recipients is high, and it is associated with a low rate of infectious complication within the first 12 weeks after transplant. Most of the recipients received a combination therapy with at least one agent active against MSSA. More studies to evaluate the optimal antimicrobial stewardship policies regarding the regimen and duration of antibiotic therapy for these patients are needed.

Disruption of GCN2 Pathway Aggravates Vascular and Parenchymal Remodeling during Pulmonary Fibrosis.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) are chronic diseases of the pulmonary parenchyma and circulation, respectively, which may coexist, but underlying mechanisms remain elusive. Mutations in the GCN2 (general control nonderepressible 2) gene (EIF2AK4 [eukaryotic translation initiation factor 2 alpha kinase 4]) were recently associated with pulmonary veno-occlusive disease. The aim of this study is to explore the involvement of the GCN2/eIF2α (eukaryotic initiation factor 2α) pathway in the development of PH during PF, in both human disease and in a laboratory animal model. Lung tissue from patients with PF with or without PH was collected at the time of lung transplantation, and control tissue was obtained from tumor resection surgery. Experimental lung disease was induced in either male wild-type or EIF2AK4-mutated Sprague-Dawley rats, randomly receiving a single intratracheal instillation of bleomycin or saline. Hemodynamic studies and organ collection were performed 3 weeks after instillation. Only significant results (P < 0.05) are presented. In PF lung tissue, GCN2 protein expression was decreased compared with control tissue. GCN2 expression was reduced in CD31+ endothelial cells. In line with human data, GCN2 protein expression was decreased in the lung of bleomycin rats compared with saline. EIF2AK4-mutated rats treated with bleomycin showed increased parenchymal fibrosis (hydroxyproline concentrations) and vascular remodeling (media wall thickness) as well as increased right ventricular systolic pressure compared with wild-type animals. Our data show that GCN2 is dysregulated in both humans and in an animal model of combined PF and PH. The possibility of a causative implication of GCN2 dysregulation in PF and/or PH development should be further studied.

NINTEDANIB CESSATION IN WAITLISTED LUNG TRANSPLANT CANDIDATES IS NOT ASSOCIATED WITH INCREASED WAITLIST MORTALITY OR PERIOPERATIVE COMPLICATIONS

NINTEDANIB CESSATION IN WAITLISTED LUNG TRANSPLANT CANDIDATES IS NOT ASSOCIATED WITH INCREASED WAITLIST MORTALITY OR PERIOPERATIVE COMPLICATIONS

Bleeding and thrombotic complications associated with anticoagulation prior to lung transplantation: a case series.

BackgroundScarce data is available on therapeutic anticoagulation (AC) in patients undergoing pulmonary transplantation. We describe our institutional experience with AC-induced coagulopathy in recipients at the time of transplantation and evaluate its impact on posttransplant outcomes.MethodsRecords of adult patients on therapeutic AC at the time of lung transplantation from January 2014 to July 2021 were reviewed. Administration of preoperative pharmacologic reversal was assessed, with adequate reversal defined as international normalized ratio (INR) ≤1.5. We evaluated the incidence of major bleeding complications [delayed sternal closure, reoperation due to bleeding, chest tube output ≥1,500 cc, ≥4 units of packed red blood cells, ≥4 units of platelets, or ≥5 units of fresh frozen plasma (FFP)], major thrombotic complications [venous thromboembolism (VTE) or other major thrombosis on imaging], and inpatient mortality.ResultsOf 602 lung transplant recipients, 10 patients taking preoperative warfarin were included in the study. While most patients received pharmacologic reversal preoperatively (n=9, 90%), successful reversal was rarely achieved (n=3, 30%). Inadequate INR reversal was associated with major bleeding events (n=6, 60%). Major thrombotic complications were more frequent (n=7, 70%) than bleeding events. Notably, all fatalities within the cohort (n=2, 20%) were associated with thrombotic, but not bleeding, complications.ConclusionsThis is the first known report on the incidence and impact of AC-induced coagulopathy in patients undergoing lung transplantation. Major thrombotic events are frequent and associated with high mortality. Routine surveillance and treatment may be warranted.

Thromboembolism After Lung Transplantation - Prolonged Anticoagulation Prophylaxis Depending on Age and Body Weight?

<h3>Purpose</h3> Thromboembolism after lung transplantation (LTX) is associated with increased morbidity and reduced long-term survival. The incidence is reported up to 43%, however, lung transplant receipients are a heterogeneous group, due to different underlying diseases and preexisting conditions. The aim of this study is to determine the incidence and outcome of thromboembolic complications and to identify independent risk factors. Here, we question whether prolonged thromboembolism prophylaxis might be beneficial in specific groups of patients. <h3>Methods</h3> We retrospectively analyzed the medical records of 221 patients who underwent LTX at our institution between 2003 and 2021. Thromboembolism was diagnosed by ultrasound, computed tomography, pulmonary angiogram (CTPA) or ventilation/perfusion scan. Statistical analysis was performed using SPSS software. <h3>Results</h3> 77 LTX recipients (35%) had at least one thromboembolic event, 65 of them (83%) within the first postoperative year. 36 (46%) patients were diagnosed with pulmonary embolism (PE), 23 (30%) with ischemic stroke. A thromboembolic event within the first postoperative month was associated with reduced post-transplant survival vs. patients without (30% vs. 58%, p=0.026). The incidence of thromboembolic events was increased in patients with a body mass index (BMI) > 25 vs. patients with a BMI < 25 (42% vs. 31%, p=0.004), especially in the first postoperative year (37% vs. 24%, p<0.001). Interestingly only 7 of 33 (21%) patients with a BMI <18.5 were diagnosed with a thromboembolic event and none of them had PE. Accordingly, we found the risk for PE to correlate with body weight (V=0.3; p < 0.001). 65% of the patients were older than 55 years at the time of lung transplantation. The incidence of thromboembolism in the first month was increased in these patients (10% vs. 13%, p=0.029), and they had reduced post-transplant survival (20% vs. 63%, p < 0.001). Notably, 48% sustained irreversible damage after the apoplex. <h3>Conclusion</h3> The incidence of thromboembolism after LTX is high and there may be devastating consequences for the patient. We identified a BMI >25 and an age > 55 years at the time of transplantation as independent risk factors, a group which likely includes the majority of recipients in most transplant centers. Prolonged thromboembolic prophylaxis after LTX for these patients should be considered.

A Comparison of Short-Term Morbidity and Mortality Among Inpatient Lung Transplant Recipients Transplanted for COVID-19 and Other Restrictive Lung Diseases

PurposePatients with respiratory failure (RF) who are hospitalized at the time of lung transplant (LTx) have higher post-LTx morbidity and mortality than those who are well enough to remain at home. Complications may be even worse in patients transplanted for COVID-19 (C19), as they are commonly critically ill having endured prolonged mechanical ventilation, ECMO support, myopathy, malnutrition, and superimposed infections. In a retrospective cohort study, we compared inpatient lung transplant recipients (LTxRs) transplanted for C19 vs. other underlying restrictive lung diseases (RLDs)MethodsAfter IRB approval, patients who underwent inpatient LTx between 1/1/2014 and 8/31/2021 were categorized by indication: C19 or RLD. We excluded LTxRs <18 years old, a primary indication for LTx other than UNOS disease group D, and redo LTx. Primary outcomes were postoperative morbidity and 90-day survival.ResultsOut of 163 inpatient LTxRs, 141 met inclusion criteria: 11 (7.8%) with C19 and 130 (92.2%) with RLD. LTxRs with C19 were younger, had a longer pre-LTx hospital stay, and more likely needed pre-LTx mechanical ventilation and ECMO support. LTxRs with C19 were also more likely to have severe adhesions intraoperatively and their chest was more commonly left open after LTx due to a perceived risk of ongoing bleeding. In addition, LTxRs with C19 had a higher prevalence of PGD3 at 72 hours and longer post-LTx hospital stays and trended toward longer post-LTx mechanical ventilation and need for inpatient rehabilitation. The 2 groups had similar 90-day survival (C19, 100% vs. RLD, 95.4%, p=0.472), however, LTxRs with C19 had a higher incidence of acute cellular rejection and DSA production (>2,000 MFI) within 6 months of transplant.ConclusionLTxRs with C19 are typically sicker and have more post-LTx complications than LTxRs with RLD hospitalized at the time of LTx. However, 90-day survival is comparable and high in both groups. Long-term follow-up is needed.

Addressing Diaphragm Dysfunction in Lung Transplant Recipients: The Expanding Role of Diaphragm Pacing

<h3>Purpose</h3> Diaphragmatic dysfunction is documented after lung transplantation and can affect up to 62% patients. Diaphragm pacing (DP) prevents ventilator induced diaphragm dysfunction (VIDD) while on mechanical ventilation (MV) and has been shown via functional electrical stimulation to improve phrenic nerve recovery. We report the largest experience of DP in lung transplantation recipients. <h3>Methods</h3> This is a retrospective analysis of an IRB approved prospective, non-randomized interventional experience at a single institution with two DP systems. A chronic DP system [NeuRx, Synapse Biomedical] was implanted laparoscopically in those with phrenic nerve injury or difficulty with weaning from MV remotely after their transplant. A temporary DP system [TransAeris, Synapse Biomedical] was implanted at the time of transplantation or laparoscopically. In both types of implantation, diaphragm stimulation ensued if needed to wean from MV or for nerve recovery. Results evaluated radiographically and with diaphragm electromyography (dEMG). <h3>Results</h3> DP was utilized in16 patients with no device adverse events. Of those, 5 patients had chronic DP system: a) 1 patient one year post transplant shows no recovery of phrenic nerve injury, still pacing; b) 3 patients showed recovery of phrenic nerve/diaphragm function through pacing; c) 1 patient 2 years post-transplant sustained hip fracture requiring surgery, developed pneumonia and became tracheostomy MV dependent; DP allowed complete diaphragm recovery, decanullation of tracheostomy and removal of DP wires. 11 patients had temporary DP electrodes placed: a) 1 recipient(two months post-transplant) had DP use during ECMO for COVID- 19 sepsis and respiratory failure and subsequently expired when family withdrew therapy; b) 10 implanted at time of lung transplant. Of those 10, 3 patients had bilateral dEMG identified post-operatively with uneventful recovery and removal of electrodes; 7 patients had diaphragm abnormalities identified post-operatively and underwent DP. Of those 7, 5 showed recovery and DP electrodes removed and 2 are still pacing 1 and 9 months post-transplant. <h3>Conclusion</h3> DP was safely used in lung transplantation to identify and improve recovery of phrenic nerve injuries, wean from MV and prevent VIDD. DP shows promise in addressing diaphragm dysfunction after lung transplantation and improving outcomes.

A survey of use of mTOR inhibitors in patients with lymphangioleiomyomatosis listed for lung transplant

BackgroundLymphangioleiomyomatosis (LAM) is an uncommon indication for lung transplantation. The use of mechanistic target of rapamycin (mTOR) inhibitors, which are the mainstay of treatment in progressive LAM, in patients awaiting lung transplant is controversial. We sought to examine worldwide practice patterns in use of mTOR inhibitors in LAM patients on the lung transplant waiting list. MethodsWe designed and disseminated an online survey about institution-specific practice patterns, particularly regarding listing LAM patients for lung transplant and use of mTOR inhibitors in those patients on the transplant waitlist. ResultsOf the 49 unique respondent programs, 83.6% had previously listed a LAM patient for lung transplant. Thirteen centers allowed patients to continue on mTOR inhibitor until time of lung transplant. None of those centers reported any complications or deaths attributable to mTOR inhibitor adverse effects. ConclusionThere exists significant variability in practice patterns concerning the use of mTOR inhibitors in LAM patients on the lung transplant waiting list. Our survey suggests favorable outcomes for those patients that did continue mTOR inhibitor up to time of transplant. Further data regarding the risk of anastomotic complication with use of mTOR inhibitors in the pre-transplant period would help provide clarity in this debate.

STAGE III ADENOCARCINOMA IN THE PNEUMONECTOMY SPECIMEN AT TIME OF LUNG TRANSPLANT RESULTING IN POSTTRANSPLANT METASTASIS DESPITE EXPLANTATION

TOPIC: Transplantation TYPE: Fellow Case Reports INTRODUCTION: Only a few reports have detailed the discovery of non-small cell lung adenocarcinoma in the explanted lung at the time of lung transplant (1). Herein, we present the case of a lung adenocarcinoma, identified in the pneumonectomy specimen, determined to have metastasized in the post-transplant period. CASE PRESENTATION: We reviewed the case of a 61-year-old Caucasian male bilateral lung transplant recipient secondary to end-stage pulmonary fibrosis and pulmonary hypertension. Evaluation of the right lung pneumonectomy specimen revealed multiple foci of lung adenocarcinoma in the right upper, middle, and lower lobes (Figure A – pre-transplant; Figure B – post-transplant). DISCUSSION: Final histopathological evaluation confirmed non-resectable lung adenocarcinoma, pT4N2M0, stage IIIB. The patient was not an ideal candidate for adjuvant radiotherapy due to post-transplant anastomosis site healing. He was also not an ideal candidate for immune checkpoint inhibitors due to insufficient evidence for safety in the solid organ transplant setting. His immunosuppression was reduced, and treatment with adjuvant chemotherapy (pemetrexed/cisplatin) was initiated. The patient suffered complications including pancytopenia and acute renal failure, although his allograft function remained stable through 6 months post-transplant. De novo-donor specific antibodies to DQA1 (20,000 MFI) were detected in sera at 6 months post-transplant, requiring plasmapheresis. At 9 months post-transplant, surveillance bronchoscopy with transbronchial biopsy to evaluate for cellular rejection revealed lung adenocarcinoma associated with lymphangitic carcinomatosis. Follow-up imaging with positron emission tomography and magnetic resonance imaging showed brain, bone, and adrenal gland metastasis. The patient is currently receiving palliative-intent chemotherapy and suffering ongoing pancytopenia and myelosuppression. CONCLUSIONS: Pre-transplant malignancies can remain unidentified due to architectural distortion of the lung parenchyma, even despite appropriately timed, aggressive radiographic surveillance. These malignancies portend worse post-transplant outcomes. REFERENCE #1: Choi YJ, Kim SY, Park MS, Lee JG, Paik HC, Lee SH. Incidental Lung Cancer of Explanted Lungs from Lung Transplant Recipients: Incidence, Characteristics, and 5-Year Survival. Yonsei Med J. 2020 Nov;61(11):958-964. doi: 10.3349/ymj.2020.61.11.958. PMID: 33107239; PMCID: PMC7593106. DISCLOSURES: No relevant relationships by Hesham Abdelrazek, source=Web Response No relevant relationships by Ashwini Arjuna, source=Web Response No relevant relationships by Michael Olson, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Grifols Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Shire Please note: $1001 - $5000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Astellas Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria

Lung transplantation outcomes after crossing low-level donor specific antibodies without planned augmented immunosuppression.

It is unknown whether some donor specific antibodies (DSA) can be crossed at the time of lung transplant without desensitization or augmented induction immunosuppression. This study assessed whether crossing low-level pre-transplant DSA (defined as mean fluorescence intensity [MFI] 1000-6000) without augmented immunosuppression is associated with worse retransplant-free or chronic lung allograft dysfunction (CLAD)-free survival. Of the 458 included recipients, low-level pre-transplant DSA was crossed in 39 (8.6%) patients. The median follow-up time was 2.2years. There were 15 (38.5%) patients with Class I DSA and 24 (61.5%) with Class II DSA. There was no difference in adjusted overall retransplant-free survival between recipients where pre-transplant DSA was and was not crossed (HR: .98 [95% CI=.49-1.99], P=.96). There was also no difference in CLAD-free survival (HR: .71 [95% CI=.38-1.33], P=.28). There was no difference in Grade 3 PGD at 72h (OR: 1.13 [95% CI=.52-2.48], P=.75) or definite or probable AMR (HR: 2.22 [95% CI=.64-7.61], P=.21). Lung transplantation in the presence of low-level DSA without planned augmented immunosuppression is not associated with worse overall or CLAD-free survival among recipients with intermediate-term follow-up.

Effect of antifibrotic therapy in patients with idiopathic pulmonary fibrosis undergoing lung transplant in the peri and post-operative period

BackgroundIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease with high mortality. Lung transplant remains a cornerstone of treatment despite the advent of antifibrotic therapy. In light of the increasing number of patients on antifibrotic therapy prior to lung transplantation it is paramount to demonstrate these medications do not augment postoperative complications following transplant. Research questionDoes antifibrotic therapy increase perioperative complications and mortality in lung transplant recipients? Study design and methodsWe conducted a retrospective chart review of all patients actively listed for lung transplant at Temple University Hospital from June 2014 to April 2017 with a listing diagnosis of IPF. Subjects who received treatment with antifibrotic therapy (either pirfenidone or nintedanib) up until the time of lung transplantation were compared to subjects not on therapy. Data was collected regarding baseline demographics, pulmonary function tests, IPF exacerbations, perioperative bleeding and cardiac events, and outcomes in the postoperative period. ResultsA total of 94 subjects were included in the study: 42 subjects on antifibrotic therapy (28 pirfenidone, 14 nintedanib) and 52 subjects not on therapy in the pre-transplant period. Baseline characteristics were similar between study groups. Subjects treated with antifibrotic therapy pre-transplant were noted to have less FVC decline, fewer hospitalizations, and greater weight loss while on the transplant waiting list. No difference in post-transplant airway anastomosis complications, bleeding or mortality was observed between study groups. InterpretationSubjects with IPF on antifibrotic therapy prior to lung transplantation had better preservation of lung function in the pre-transplant period, and similar outcomes in the postoperative period compared to those not on antifibrotic therapy before lung transplant.

Reply: Ensuring pulmonary artery patency in donor-recipient size mismatch: A collaborative challenge.

Vascular anastomosis during lung transplantation is a critical issue that directly affects postoperative graft function. The use of transesophageal echocardiography (TEE) to establish clear criteria for a possible size mismatch between donor and recipient pulmonary artery (PA) diameters at the time of lung transplantation, as reported by Kumar and colleagues1 in this study, is a method that holds great promise for the future. We introduced 4 new PA vascular anastomosis techniques that could be implemented upon recognition of a size mismatch in PA diameter at the time of lung transplantation; however, we failed to discuss how a surgeon may optimize technique selection.

Incidentally Detected Chronic Lymphocytic Leukemia in Hilar Lymph Nodes at the Time of Lung Transplantation: A Case Report

A 68-year-old man with interstitial pulmonary fibrosis underwent bilateral lung transplantation. Histopathologic examination of hilar lymph nodes in the explanted lungs showed effacement of normal nodal architecture by the proliferation of small lymphocytes, consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Unexpectedly discovered malignancies at the time of lung transplantation is uncommon, especially in the lymph nodes. The clinical management was challenging because of attempts to balance treatment of CLL and immunosuppressive treatment to prevent graft rejection. Here, we report a case of incidentally detected CLL in hilar lymph nodes with explanted lungs and review the relevant literature.

Phosphoproteomic analysis of lung tissue from patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disorder associated with high morbidity and mortality despite currently available treatments. We compared the phosphoproteome of lung tissue from subjects with idiopathic PAH (iPAH) obtained at the time of lung transplant with control lung tissue. The mass spectrometry-based analysis found 60,428 phosphopeptide features from which 6622 proteins were identified. Within the subset of identified proteins there were 1234 phosphopeptides with q < 0.05, many of which are involved in immune regulation, angiogenesis, and cell proliferation. Most notably there was a marked relative increase in phosphorylated (S378) IKZF3 (Aiolos), a zinc finger transcription factor that plays a key role in lymphocyte regulation. In vitro phosphorylation assays indicated that GSK3 alpha and/or GSK3 beta could phosphorylate IKZF3 at S378. Western blot analysis demonstrated increased pIKZF3 in iPAH lungs compared to controls. Immunohistochemistry demonstrated phosphorylated IKZF3 in lymphocytes surrounding severely hypertrophied pulmonary arterioles. In situ hybrization showed gene expression in lymphocyte aggregates in PAH samples. A BCL2 reporter assay showed that IKZF3 increased BCL2 promoter activity and demonstrated the potential role of phosphorylation of IKZF3 in the regulation of BCL mediated transcription. Kinase network analysis demonstrated potentially important regulatory roles of casein kinase 2, cyclin-dependent kinase 1 (CDK1), mitogen-associated protein kinases (MAPKs), and protein kinases (PRKs) in iPAH. Bioinformatic analysis demonstrated enrichment of RhoGTPase signaling and the potential importance of cGMP-dependent protein kinase 1 (PRKG). In conclusion, this unbiased phosphoproteomic analysis demonstrated several novel targets regulated by kinase networks in iPAH, and reinforced the potential role of immune regulation in the pathogenesis of iPAH. The identified up- and down-regulated phosphoproteins have potential to serve as biomarkers for PAH and to provide new insights for therapeutic strategies.