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Background. SARS-CoV-2 can result in a range of infections from asymptomatic disease to progressive COVID-19 and death. In some pts with CALI, lung transplantation (LTx) may be lifesaving. Up to 10% of LTx in the US is currently for pts with CALI. Understanding the characteristics and outcomes of these pts is critical. Methods. A open-access electronic registry was established to collect deidentified data from pts who have undergone LTx for CALI from centers globally. The study was IRB approved at Northwestern with a wavier for consent (no PHI is collected sites could submit data about pre-Tx, peri-Tx and post-Tx course). Follow-up for 1-yr post-LTx was collected. Results. To date, 89 pts with complete day 30 post-LTx data have been entered into the registry. Pt demographics and pre-Tx status are shown in Table 1. 3 pts required oxygen prior to COVID-19. Most sites required neg PCR tests prior to listing (11 (12.4%) required no - PCRs, 11 (12.4%) required 1 and 61 (68.5%) required 2). LTx occurred 137 days post-infection and none developed COVID-19 in the first 30 d;4 were given monoclonal antibodies post-tx. Post-tx ICU LOS averaged 24.5 d with total post-tx hospitalization of 37.6 d (See Table 2). Most experienced infectious and noninfectious morbidity. Most (47.8%) required an additional 30 days of rehab. 2 pts died within 30 days due to sepsis and anoxia. 5 died between day 30 and 90 and an additional 12 died between day 90 and 365. Conclusion. The contribution of cases to this international registry is ongoing. While outcomes of LTx for CALI are generally good, patients experience prolonged post-transplant hospitalization, rehabilitation and significant morbidity and infections are common. (Table Presented).
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SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Donor-derived cell-free DNA (dd-cfDNA) is a promising plasma analyte for surveillance of rejection and lung transplant (LT) injury. Herein we report our preliminary real-world experiences in concert with standard of practice (SOP) assessments. METHODS: We performed a prospective, cross-sectional, cohort study of a clinically available dd-cfDNA test (the Prospera™ test, Natera, Inc.) combined with SOP clinical assessments − spirometry, fiberoptic bronchoscopy (FOB), donor-specific HLA antibodies (DSA). Single LT dd-cfDNA results were corrected (2X) for lung mass before analysis. Clinical-pathologic cohorts were assigned based on ISHLT guidelines for acute cellular rejection (ACR), uncomplicated chronic lung allograft dysfunction (U-CLAD), and either CoVid-19 or Non-CoVid-19 allograft infection. We also compared median dd-cfDNA fractions between patients experiencing allograft dysfunction (AD) (defined by ΔFEV1≥ -10%) vs stability (STA) and stratified by DSA status. Groups were analyzed by Mann-Whitney (p<0.05) and data expressed as median with 25-75% interquartile range (IQR). RESULTS: A total of 54 plasma samples from 42 unique LT recipients (Single=6, Double=36) were collected at Spectrum Health between November 2021 and February 2022. Primary diagnoses included chronic obstructive pulmonary disease (n=7), interstitial lung disease (n=31), CoVid-19 related ARDS (n=2), CF (n=1) and PAH (n=1). Matching histopathology was available for 68% of dd-cfDNA samples. dd-cfDNA fraction trended 2-fold higher in patient with ACR (1.59%, IQR: 0.09-3.57;n=3) and U-CLAD (1.88%, IQR: 0.88-3.32;n=4) than STA (0.86%, IQR: 0.21-1.62;n=14) patients. Patients with CoVid-19 had significantly higher dd-cfDNA fraction (6.91%, IQR: 2.41-9.77;n=4) than both STA (p=0.035) and NON-CoVid-19 infection cohorts (p=0.049). Although no antibody-mediated rejection (AMR) events were observed, dd-cfDNA fraction was significantly elevated in DSA(+) patients (2.75%, IQR: 1.72-6.25;n=8, class I (4) and II (4)) vs DSA(-) (1.035%, 0.04-1.64;n=46) cohorts (p=0.011). A trend was noted with elevated dd-cfDNA with AD (1.58%, IQR: 0.74-3.62;n=17) vs AS (1.05%, 0.66-1.79;n=37) (p=0.29). CONCLUSIONS: Our preliminary experience is consistent with prior studies, suggesting elevated dd-cfDNA fraction during LT allograft rejection and specific types of infection, in particular, CoVid-19. Of interest, dd-cfDNA detected potential occult molecular injury associated with anti-HLA DSA. CLINICAL IMPLICATIONS: dd-cfDNA fraction assessment after LT represents a valuable clinical tool for clinical surveillance of organ transplant health. DISCLOSURES: Employee relationship with Veracyte, Inc Please note: 2 years by Sangeeta Bhorade, value=Salary Removed 04/03/2022 by Sangeeta Bhorade Employee relationship with Natera Inc Please note: 2/22/22- present Added 04/03/2022 by Sangeeta Bhorade, value=Salary Employee relationship with Natera Please note: 05/2021-present Added 04/04/2022 by Kathryn Crabtree, value=Salary research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria no disclosure on file for Cameron Lawson;No relevant relationships by Edward Murphy Employee relationship with Natera, Inc. Please note: 2020- present by David Ross, value=Salary
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SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Fibrotic interstitial lung disease (fILD) can be idiopathic or associated with several underlying conditions and in response to various types of injury. Post COVID-19 fILD is an increasingly recognized clinical entity with the potential for a large burden of morbidity and mortality.[1] We present a series of 6 patients with progressive pulmonary fibrosis as sequela of COVID-19 requiring lung transplantation. CASE PRESENTATION: Four of the 6 patients had known underlying chronic ILD prior to COVID-19 infection (2 with idiopathic pulmonary fibrosis [IPF] and 1 each with scleroderma and rheumatoid arthritis associated ILD). The other 2 patients had no prior history of lung disease and asymptomatic before infection. One of these had a strong family history of IPF. The presentations involved signs of progressive respiratory failure after the initial lung injury from COVID-19. 4 patients were hospitalized during their acute COVID-19 illness and had varying treatments including steroids, antibiotics, anti-virals, convalescent plasma, Tocilizumab, and non-invasive positive pressure ventilation. At the time of transplant evaluation, CT imaging showed prominent interstitial thickening, honeycombing consistent with fibrotic processes for all our patients;PFT revealed severe restrictive ventilatory defect with reduced diffusion capacity ranging 24%-53%;3 patients required venous-venous extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation for 14 and 93 days. The remainder required 6-10 L of supplemental oxygenation at rest. Two patients underwent initial transplant evaluation while in respiratory failure.5 patients received bilateral lung transplantation and one single left lung transplantation.Duration of time between initial COVID-19 induced lung injury and transplantation ranged from 3-13 months, with a median 6-7 months.Lung explant pathology showed advanced usual interstitial pneumonia in all. Superimposed diffuse alveolar damage was noted in 3 cases. Post-transplant to discharge ranged 10-31 days and at 2 months follow-up, all patients were liberated of oxygen needs. All subjects remain alive at a median 11-12 months, with no evidence of allograft dysfunction. DISCUSSION: Since the emergence of SARS-COV2 in 2019, histopathological fibrotic anomalies have been found to be present in up to one-third of those who recover from ARDS due to COVID-19 [2] and their incidence increases as duration of ARDS increases [3]. Further work is required to understand the pathogenesis of the fibrotic process following acute COVID-19. CONCLUSIONS: We highlight this syndrome with our case series of 6 patients who showed progressive fibrotic disease after COVID-19. Patients with pre-exiting ILD appear to be particularly at risk but this entity may occur in those without pre-existing ILD. Lung transplantation offers a viable treatment option for selected patients with an otherwise poor prognosis. Reference #1: 1.Bharat, A., Querrey, M., Markov, N. S., Kim, S., Kurihara, C., Garza-Castillon, R., Manerikar, A., Shilatifard, A., Tomic, R., Politanska, Y., Abdala-Valencia, H., Yeldandi, A. V., Lomasney, J. W., Misharin, A. V., & Budinger, G. (2020). Lung transplantation for pulmonary fibrosis secondary to severe COVID-19. medRxiv : the preprint server for health sciences, 2020.10.26.20218636. https://doi.org/10.1101/2020.10.26.20218636 Reference #2: 2. Rai DK, Sharma P, Kumar R. Post covid 19 pulmonary fibrosis. Is it real threat?. Indian J Tuberc. 2021;68(3):330-333. doi:10.1016/j.ijtb.2020.11.003 Reference #3: 3. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, MacKenna B, Tomlinson L, Douglas IJ, Rentsch CT, Mathur R, Wong AYS, Grieve R, Harrison D, Forbes H, Schultze A, Croker R, Parry J, Hester F, Harper S, Perera R, Evans SJW, Smeeth L, Goldacre B. Factors associated with C VID-19-related death using OpenSAFELY. Nature. 2020 Aug;584(7821):430-436. doi: 10.1038/s41586-020-2521-4. Epub 2020 Jul 8. PMID: 32640463;PMCID: PMC7611074. DISCLOSURES: no disclosure on file for Philip Camp;research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria No relevant relationships by Ryan Hadley No relevant relationships by Sheila Krishnan No relevant relationships by Sheetal Maragiri No relevant relationships by Edward Murphy No relevant relationships by Jay Patel No relevant relationships by Keval Ray No relevant relationships by Gayathri Sathiyamoorthy No relevant relationships by Neel Shah No relevant relationships by Subhan Toor
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SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Immunosuppressed patients are more susceptible to severe infection due to COVID-19. Management of lung transplant recipients is especially difficult due to constant exposure of the graft to the environment, leading to increased risk of rejection and requiring higher levels of maintenance immunosuppressive regimens. Mortality rates for lung transplant recipients with COVID-19 infection have ranged from 15% to 40% in published case series. We report our centers experience in managing lung transplant recipients with COVID-19 infections in a moderate-volume lung transplant center in Grand Rapids, Michigan. METHODS: This is a single center review of all lung transplant recipients with a COVID-19 diagnosis from March 2020 to December 2021. Recipients’ demographics and baseline characteristic, as well as their management, post infectious complications, and mortality data, were reviewed. RESULTS: In 2019, our center performed 48 lung transplants. During the study period, 42 of the 219 (19%) lung transplant recipients followed at our center had COVID-19 infections diagnosed by nasal or nasopharyngeal PCR testing. Twenty-four (57%) were male, mean age of 60.5 (range 25-77). Thirty-six (86%) patients had bilateral lung transplants. The diagnosis leading to their transplantation were COPD (N=18, 43%), idiopathic pulmonary fibrosis (N=12, 29%), cystic fibrosis (N=5, 12%), other pulmonary fibrosis (N=3, 7%), alpha-1 antitrypsin deficiency (N=2, 5%), Sarcoidosis (N=1, 2%), and ARDS (N=1, 2%). Almost all patients were on standard three drug immunosuppressive regimens which included a steroid, calcineurin inhibitor, and nucleotide-blocking agent, at the time of diagnosis. Mean time from transplant to diagnosis of COVID-19 was 34.6 months (range 1 to 104 months). Fifteen (36%) of the patients were unvaccinated. Once diagnosed, patients were advised to monitor their home spirometry and vitals at least daily. They were evaluated weekly via telemedicine by a physician or advanced practice provider. They received the following treatments: monoclonal antibody (N=31, 74%), increased steroids (N=5, 12%), remdesivir (N=2, 5%), Tocilizumab (N=1, 2%). Eleven (26.2%) patients required hospitalization, 4 (10%) required ICU admission and intubation. Mean length of stay was 7.5 days (median of 3 days). Three (7%) patients required oxygen at discharge. Of the 42 infected patients, 3 (7.1%) died on day 3, 16 and 326 days from the date of infection. CONCLUSIONS: Our center reports a lower mortality rate than previously published data in lung transplant recipients infected with COVID-19. We attribute this to availability of the vaccine, early detection and treatment, as well as close monitoring of the patients. CLINICAL IMPLICATIONS: Though COVID-19 infection can have devastating complications in lung transplant recipients, vaccinations and monoclonal antibody treatment reduce morbidity and mortality in this population. DISCLOSURES: No relevant relationships by Phillip Camp research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria no disclosure on file for Ryan Hadley;No relevant relationships by Sheila Krishnan No relevant relationships by Edward Murphy No relevant relationships by Gayathri Sathiyamoorthy
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Introduction: Persistent radiographic and pulmonary function abnormalities are increasingly recognized following Corona Virus Disease (COVID-19) pneumonia. We present a case of rapidly progressive pulmonary fibrosis in a Usual Interstitial Pneumonia (UIP) pattern. Successful lung transplantation was performed two months following COVID-19 infection. Description: 68 years old with known history of mild Interstitial Lung Disease (ILD) , not on home oxygen, initially presented in July 2020 with worsening shortness of breath and cough. There was a strong family history for Interstitial pulmonary fibrosis (IPF). Her last pulmonary function tests showed a Forced Expiratory Volume in one second (FEV1) of 2.24 Liters (99%) and Forced Vital Capacity of 2.69 Liters (92%). Her last High Resolution Computed Tomography (HRCT) showed chronic stable mild interstitial fibrosis. On admission, she was positive for COVID 19 on her Polymerase Chain Reaction (PCR). Initial CT chest showed diffuse new ground glass changes. She was treated with remdesavir, dexamethasone and antibiotics. She did not require endotracheal intubation and showed improvement in her symptoms. Unfortunately, she could not be weaned off oxygen and was discharged on six liters flow oxygen through a nasal cannula. She presented again to the hospital, one month later with worsening shortness of breath. Her PCR was negative for COVID 19. Her CT angiogram of thorax however showed interval worsening of her interstitial changes. An urgent inpatient evaluation for lung transplantation was completed and she deemed to be a suitable candidate. After 4 days into her stay, acute deterioration in her respiratory status developed with tachypnea and increased work of breathing requiring endotracheal intubation and mechanical ventilation. Repeat CT chest showed fibrotic interstitial disease with associated traction bronchiectasis and a large amount of ground glass. She was subsequently placed on veno-venous Extra Corporeal Membrane Oxygenation (VV ECMO) which allowed extubation. A donor offer for bilateral lungs was accepted after one day on ECMO. She successfully underwent bilateral lung transplant in September 2020. Her post-operative course was uncomplicated. She is doing well 3 months post transplant without evidence of cellular rejection. Her explant pathology showed Diffuse Alveolar Damage plus UIP Discussion: Persistent and progressive pulmonary fibrosis may develop following COVID-19 pneumonia. Risk factors may include underlying ILD and family history of IPF. In suitable candidates, lung transplantation is a viable option.
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SESSION TITLE: Transplantation Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Chronic lung allograft dysfunction (CLAD) remains the leading cause of long-term mortality after lung transplantation (LTX) with no proven therapeutic strategies except re-transplantation. Anecdotal reports suggest a role for the lymphocyte depleting agent, Alemtuzumab (AL), an anti-CD52 monoclonal antibody. We reviewed our experience with AL for the treatment of refractory CLAD. METHODS: Eight consecutive LTX recipients were identified. AL was given as a single subcutaneous dose of 30 mg. Cell-cycle inhibitor therapy was held and valganciclovir and azole prophylaxis were given for at least 6 months after AL treatment. The slope of FEV1 3 months before and after AL were compared. Complications of AL therapy including infections and survival were assessed. RESULTS: The cohort consisted of 5 males and 3 females with a median age at time of AL administration of 66 y (range: 50-72). Time post-transplant was 2.43 y (range: 1.4-5.4). Pre-transplant diagnoses were COPD (n=3), and 1 each of CF, bronchiectasis (immotile cilia syndrome), IPF, PVOD and IPAH. All subjects were bilateral recipients and 1 was post-left pneumonectomy early after transplant. All had a predominantly obstructive CLAD phenotype, stages 4 (N=2), 3 (N=4), 2 (N=1) and 1 (N=1) with rapid loss of lung function. The median slope of decline in FEV1 in the 3 months prior to AL was -336ml/m (range: -39 to -552) compared with +24 ml/m (range: -171 to +48) during the 3 months post AL administration (P = 0.016). No acute reactions to AL treatment were observed. Clinically symptomatic infections occurred in 4 patients following AL. Community acquired respiratory viral infections were observed in 2 (parainfluenza and coronavirus on 2 separate occasions in 1 patient and rhinovirus in another). Pseudomonas tracheobronchitis developed in 1. These infections were considered mild-moderate. One subject developed new parenchymal opacities with isolation of Rasamsonia argillacea and Mycobacterium fortuitum. Two patients died due to progressive CLAD 3 and 6 months after AL. The other six are alive at a median follow-up time of 12 months (range: 7 – 20). Kaplan-Meier survival estimate at one year was 75%. At last follow-up, CLAD stages among survivors was 4 (N=1), 3 (N=4) and 2 (N=1). CONCLUSIONS: AL therapy was associated with a significant attenuation in lung function decline in lung transplant recipients with rapidly progressive CLAD. Treatment was generally well tolerated with few serious infection complications. CLINICAL IMPLICATIONS: AL should be considered for rapidly progressive CLAD. Randomized controlled trials are required to establish efficacy and safety. DISCLOSURES: No relevant relationships by Reda Girgis, source=Web Response No relevant relationships by Ryan Hadley, source=Web Response no disclosure submitted for Anupam Kumar;No relevant relationships by Cameron Lawson, source=Web Response no disclosure on file for Marzia Leacche;No relevant relationships by Jennifer McDermott, source=Web Response no disclosure on file for Edward Murphy;No relevant relationships by Gayathri Sathiyamoorthy, source=Web Response