Pulmonary Pathology of End-Stage COVID-19 Disease in Explanted Lungs and Outcomes After Lung Transplantation
OBJECTIVES/OBJECTIVE:Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due to postacute sequelae of SARS-CoV-2 infection. METHODS:A retrospective histologic evaluation of explanted lungs due to coronavirus disease 2019 was performed. RESULTS:None of the patients had known prior pulmonary disease. The major pathologic findings in the lung explants were proliferative and fibrotic phases of diffuse alveolar damage, interstitial capillary neoangiogenesis, and mononuclear inflammation, specifically macrophages, with varying numbers of T and B lymphocytes. The fibrosis varied from early collagen deposition to more pronounced interstitial collagen deposition; however, pulmonary remodeling with honeycomb change was not present. Other findings included peribronchiolar metaplasia, microvascular thrombosis, recanalized thrombi in muscular arteries, and pleural adhesions. No patients had either recurrence of SARS-CoV-2 infection or allograft rejection following transplant at this time. CONCLUSIONS:The major pathologic findings in the lung explants of patients with SARS-CoV-2 infection suggest ongoing fibrosis, prominent macrophage infiltration, neoangiogenesis, and microvascular thrombosis. Characterization of pathologic findings could help develop novel management strategies.
Primary Cytomegalovirus Infection in a Low-Risk Lung Transplant Recipient Manifesting as a Pleural Effusion [Meeting Abstract]
Introduction: Community-acquired Cytomegalovirus (CMV) infection in a seronegative transplant recipient (R) from a seronegative donor (D) is a rare occurrence that carries significant clinical and prognostic implications. Few case reports exist describing this entity in lung transplant recipients. Case Report: A 58-year-old man with bilateral lung transplant for sarcoidosis presented with three days of diarrhea and dyspnea. He underwent an uneventful bilateral lung transplantation (CMV D-/R-) six weeks prior, receiving basiliximab and methylprednisolone for induction. He was discharged two weeks later on tacrolimus, mycophenolate motefil, and prednisone taper as maintenance immunosuppression. He was receiving acyclovir for herpes viruses prophylaxis. He was seen weekly post-discharge and continued to have clear chest radiographs and unremarkable bloodwork. On presentation, his physical examination was notable for decreased breath sounds at the right base. His laboratory values revealed creatinine of 2.4 mg/dL. His chest radiograph showed new right pleural effusion. He was admitted for hydration and diarrhea work up. Abdominal computed tomography (CT) revealed mild diverticulitis with no colitis and his stool studies were positive for Clostridium difficile. Chest CT showed hazy and linear markings with thin-walled cysts in right lower lobe, adjacent to a moderate pleural effusion. CMV by polymerase chain reaction resulted at 318,200 copies/mL. He was treated with intravenous ganciclovir and underwent a thoracenthesis. Half a liter of clear pleural fluid was removed and was notable for lymphocytic predominance of 72% as well as polytypic plasma cells and a small number of B lymphocytes with no surface immunoglobulins on flow cytometry. Subsequent radiograph showed completely re-expanded lung. Within two days, the effusion re-accumulated and additional half a liter were drained, revealing of 95% lymphocytes, with complete re-expansion of the lung. Concomitant viral load remained elevated at 150,328 copies/mL. He was discharged on valganciclovir, his viral load decreased to an undetectable level, and his radiographs have remained free of effusion. While primary CMV infection is rare in low-risk lung transplant recipients, CMV disease should be considered in the differential diagnosis of early post-operative pleural effusion.
Multimodal opioid-sparing pain management after lung transplantation and the impact of liposomal bupivacaine intercostal nerve block
Opioid analgesics are commonly used post-lung transplant, but have many side effects and are associated with worse outcomes. We conducted a retrospective review of all lung transplant recipients who were treated with a multimodal opioid-sparing pain protocol. The use of liposomal bupivacaine intercostal nerve block was variable due to hospital restrictions. The primary objective was to describe opioid requirements and patient-reported pain scores early post-lung transplant and to assess the impact of intraoperative liposomal bupivacaine intercostal nerve block. We treated 64 lung transplant recipients with our protocol. Opioid utilization decreased to a mean of 43 milligram oral morphine equivalents by postoperative day 4. Median pain scores peaked at 4 on postoperative day 1 and decreased thereafter. Only three patients were discharged home with opioids, all of whom were taking opioid agonist therapy pre-transplant for opioid use disorder. Patients who received liposomal bupivacaine intercostal nerve block in the operating room had a significant reduction in opioid consumption over postoperative day 1 through 4 (228Â mg vs. 517Â mg, P=Â .032). A multimodal opioid-sparing pain management protocol is feasible and resulted in weaning of opioids prior to hospital discharge.
High Lung Transplant Center Volume is Associated with Increased Survival in Hospitalized Patients
BACKGROUND:The lung allocation score (LAS) was designed to optimize the utilization of pulmonary allografts based on anticipated pre-transplant survival and post-transplant outcome. Hospital admission status, not included in the LAS, has not been comprehensively investigated with regards to organ allocation. The objective of this study was to determine if pre-transplant hospital admission status is independently associated with post-transplant mortality and to determine if high center volume is associated with improved survival in that cohort.background METHODS: All consecutive adult lung transplants provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Group stratification was performed based on admission status at the time of transplantation. A Cox proportional hazard regression was used to determine independent associations with post-transplant mortality. RESULTS:During the study period, 20% (3,747/18,416) of recipients were admitted to the hospital at the time of transplantation. Compared to non-admitted recipients, LAS were significantly higher and waitlist times significantly shorter. Admitted recipients had higher rates of prolonged mechanical ventilation, higher rates of post-transplant dialysis, and longer post-transplant lengths of stay. Pre-transplant admission to a low volume center conferred significantly worse survival compared to non-admitted patients, and high volume centers were independently associated with improved survival compared to low volume centers.results CONCLUSIONS: Hospital admission status is associated with increased post-transplant mortality independent from the LAS and the factors from which it is calculated. However, adjusted survival analysis demonstrates that admission to a high volume center appears to be independently associated with improved survival compared to low volume centers. CONCLUSION/CONCLUSIONS/:
A Simple Prioritization Change to Lung Transplant Allocation May Result in Improved Outcomes
BACKGROUND:The Lung Allocation Score (LAS) significantly improved outcomes and waitlist mortality in lung transplantation. However, mortality remains high for the sickest waitlist candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system has met significant resistance, and would require years to implement. This study evaluates if a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered waitlist mortality. METHODS:The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within 250 nautical-mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LASâ‰¥50 (high-LAS) to be prioritized within a 500 nautical-mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary endpoints were waitlist mortality and post-transplant 1-year survival. RESULTS:6,538 waitlist candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in waitlist mortality. Post-transplant 1-year survival was minimally affected. CONCLUSIONS:Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased waitlist mortality and increased organ utilization. Importantly, these changes do not appear to lead to clinically significant changes in post-transplant 1-year survival.
Management and tolerability of glecaprevir-pibrentasvir pharmacotherapy in hepatitis C viremic heart and lung transplant recipients
We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient, and discontinued in another, due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.
Enhanced Recovery and Opioid-Sparing Pain Management Following Lung Transplantation
PURPOSE: Adequate pain control is essential following lung transplantation to reduce patient stress and minimize perioperative complications. Enhanced recovery after surgery (ERAS) protocols have demonstrated improvements in patient experience and reduced length of stay. However, the implementation of these protocols has not yet extended to the lung transplant population.
METHOD(S): We retrospectively reviewed all lung transplant recipients (LTR) at our institution from February 2018 to August 2019. An opioid-sparing, multimodal pain regimen was implemented that included preemptive analgesia with gabapentin and acetaminophen (APAP) pre-transplant; liposomal bupivacaine intercostal nerve block (INB) in the operating room; and a combination of APAP, gabapentin, and methocarbamol post-op with opioids given as indicated. Serratus anterior plane block was used for refractory pain.
RESULT(S): In total, we reviewed 48 LTR. The mean LAS was 43.74 and 21% were on mechanical ventilation or ECMO pre-transplant. Frequency of protocol adherence for each agent was as follows: liposomal bupivacaine INB (71%), APAP (100%), gabapentin (98%), methocarbamol (27%), and ketorolac (33%). Seven patients (15%) required a serratus plane block for refractory pain. Pain scores peaked at a median of 5 on postoperative day (POD) 1 and declined to a median of 3 by POD 3. By POD 4 only 54% of patients were still receiving opioids at a median of 15 mg oral morphine equivalents per day (IQR, 0-59). Only 3 patients were discharged on opioids and they were all on opioids pre-transplant. The median duration of mechanical ventilation was 1 day (IQR, 0.64-1.69) and 81% were extubated before 48 hours. The median hospital length of stay was 8 days (IQR, 6-15) and 30-day mortality was 0%.
CONCLUSION(S): Enhanced recovery and opioid-sparing pain protocols are feasible in LTR leading to minimal opioid use and acceptable pain scores. Outcomes with ERAS protocols should be compared to standard-of-care postoperative management.
Telehealth and Home Monitoring in Lung Transplant
PURPOSE: We hypothesize that home monitoring and telehealth utilizing data from a mobile healthcare application in conjunction with laboratory values and chest imaging, can replace an outpatient appointment.
METHOD(S): Our study is comprised of patients who have received a single or bilateral lung transplant or a heart/lung transplant.Before our patients are discharged from their inpatient stay after Transplantation, the application for home monitoring is installed on their smart phone. This application was specifically designed for Lung Transplant Patients. A blood pressure cuff and spirometer are provided and linked to their mobile device using Bluetooth. A weighing scale is also provided which uses a cellular connection to a secure cloud relaying data to the patient's phone and to EPIC. Additional data including (e.g. temperature, pulse oximetry) are manually entered into the application. Physical fitness (steps) is also monitored. The team who created the application enabled the data to flow from the application to our electronic medical record. Alerts are set for each piece of data and any abnormal value is sent to our team's EPIC in-basket for further action.Patients who are compliant with their home monitoring are offered telehealth. Patients are sent for laboratory testing and imaging the week of the appointment close to their home.
RESULT(S): As of October 1, 2019, we have enrolled fifty patients in our home monitoring program. Fourteen patients are now one - year post transplant. Twelve of these patients are compliant with home monitoring. Eight of them have had telehealth visits throughout the year with five receiving the majority of their care utilizing home monitoring and telehealth. These visits occur bimonthly for the first three months after transplant and then monthly for the first year.
CONCLUSION(S): Home monitoring and telehealth visits can replace outpatient visits in the first year following lung transplantation. Patients find the devices easy to use and are satisfied with the care they receive during their telehealth visits. Additionally, telehealth improves patient quality of life by reducing visits to the medical center and avoiding additional costs such as parking and time off work. It also limits pathogen exposure. Long term use may enable early detection of rejection or infection.
Efficacy and Tolerability of Isavuconazole versus Posaconazole for Fungal Prophylaxis after Lung Transplantation
PURPOSE: Azole antifungals are commonly prescribed for fungal prophylaxis (ppx) following lung transplant, but have many side effects and drug interactions. Isavuconazole, a new broad-spectrum azole antifungal, may obviate these issues.
METHOD(S): We retrospectively reviewed all lung transplant recipients (LTR) from February 2018 through September 2019 who received either ISA or POS for fungal ppx for 3 months post-transplant. Prior to February 2019 all patients received POS for ppx. Starting February 2019, POS was replaced by ISA at standard dosing. All patients received basiliximab induction and standard triple immunosuppression post-transplant. Surveillance bronchoscopies were performed at 1, 3, 6, and 12 months post-transplant.
RESULT(S): In total, we reviewed 24 LTR who received ISA and 29 who received POS. Baseline characteristics were similar between groups. Median duration of follow-up was significantly shorter for the ISA group (137 vs. 340 days, p<0.01). Breakthrough fungal infections occurred in 3 (13%) and 2 (7%) patients in the ISA and POS groups, respectively (p=0.65). All ISA patients developed oropharyngeal candidiasis; in the POS group there was one each of candida empyema and mold colonization. Post-ppx fungal infections occurred in 1 (4%) and 5 (17%) patients in the ISA and POS groups, respectively (p=0.20). All of these were mold colonization except for one case of oropharyngeal candidiasis. There was no difference between fungal-infection free survival based on Kaplan-Meier analysis (p=0.69). POS was held in two cases and discontinued in 1 patient due to a drug interaction causing hepatotoxicity compared to zero patients receiving ISA (p=0.24).
CONCLUSION(S): Breakthrough fungal infections were similar between LTR receiving ISA or POS for fungal ppx. Longer follow-up of ISA patients is needed for definitive comparison of long-term infection risk. POS was discontinued in more patients due to drug interactions. ISA is a reasonable choice for primary fungal ppx in LTR.
Single And Double Lung Transplantation Have Equivalent Survival for Idiopathic Pulmonary Fibrosis
BACKGROUND:Several studies have described improved survival with double lung transplantation (DLT) compared to single lung transplantation (SLT) in pulmonary fibrosis. To avoid the innate selection bias of including patients exclusively listed for SLT or DLT, this study analyzed those deemed appropriate for either procedure at time of listing. METHODS:All consecutive adult lung transplants for idiopathic pulmonary fibrosis (IPF) provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (N=11), or patients listed only for SLT (N=1834) or DLT (N=2372) were excluded. Group stratification was based on the ultimate procedure (SLT vs DLT). Group propensity matching was performed based on 24 recipient/donor characteristics. Recipient demographics, donor demographics, and outcomes were compared between groups. RESULTS:During the study period, 45% (974/2179) and 55% (1205/2179) of patients ultimately received SLT and DLT, respectively. After propensity matching, 466 matched patients remained in each group. SLT patients were less likely to require prolonged (>48 hours) ventilator support than DLT patients. There was also a trend towards reduced rates of post-transplant renal failure and hospital length of stay in SLT recipients. Whether analyzed by time of listing or time of transplant, survival was similar between groups. CONCLUSIONS:In recipients concurrently listed for SLT and DLT, overall survival was similar regardless of the eventual procedure. These data suggests that the previously purported survival advantage for DLT may purely represent selection bias, and should not preclude the use of SLT in appropriately-selected IPF patients.