Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) ...attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.
We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.
Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.
The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.
National Institutes of Health. VIDEO ABSTRACT.
Background Single-lung transplantation (SLT) and bilateral lung transplantation (BLT) are both good options for patients with end-stage lung disease secondary to idiopathic pulmonary fibrosis. It is, ...however, unclear whether BLT offers any survival advantage over SLT. The purpose of our study was to evaluate a large group of patients to determine if either SLT or BLT officered a long-term survival advantage for patients with IPF. Methods This was an Institutional Review Board-approved retrospective analysis of the United Network of Organ Sharing database from 1987 to 2008. Survival was determined using Kaplan-Meir estimates and the effect of laterality was determined by Cox proportional hazards and propensity analyses. Results Lung transplantation for idiopathic pulmonary fibrosis was performed in 3,860 patients (2,431 SLTs and 1429 BLTs). Multivariate and propensity analysis failed to show any survival advantage for BLT (hazard ratio = 0.90, 95% confidence interval = 0.78 to 1.0, p = 0.11). One-year conditional survival favored BLT (hazard ratio 0.73, 95% confidence interval 0.60 to 0.87, p = 0.00064). Risk factors for early death included recipient age over 57 and donor age over 36 years. Conclusions Bilateral lung transplantation should be considered for younger patients with idiopathic pulmonary fibrosis and results may be optimized when younger donors are used.
Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRI) and is a risk factor for the development of bronchiolitis obliterans syndrome (BOS) after lung ...transplantation (LTx). Currently, the most widely used therapy for RSV is inhaled ribavirin. However, this therapy is costly and cumbersome. We investigated the utility of using oral ribavirin for the treatment of RSV infection after LTx.
RSV was identified in nasopharyngeal swabs (NPS) or bronchoalveolar lavage (BAL) using direct fluorescent antibody (DFA) in 5 symptomatic LTx patients diagnosed with LRI. Data were collected from December 2005 and August 2007 and included: age; gender; type of LTx; underlying disease; date of RSV; pulmonary function prior to, during and up to 565 days post-RSV infection; need for mechanical ventilation; concurrent infections; and radiographic features. Patients received oral ribavirin for 10 days with solumedrol (10 to 15 mg/kg/day intravenously) for 3 days, until repeat NPS were negative.
Five patients had their RSV-LRI diagnosis made at a median of 300 days post-LTx. Mean forced expiratory volume in 1 second (FEV(1)) fell 21% (p < 0.012) during infection. After treatment, FEV(1) returned to baseline and was maintained at follow-up of 565 days. There were no complications and no deaths with oral therapy. A 10-day course of oral ribavirin cost $700 compared with $14,000 for nebulized ribavirin at 6 g/day.
Treatment of RSV after LTx with oral ribavirin and corticosteroids is well tolerated, effective and less costly than inhaled ribavirin. Further studies are needed to directly compare the long-term efficacy of oral vs nebulized therapy for RSV.
Primary graft dysfunction (PGD) following lung transplantation is clinically similar to the acute respiratory distress syndrome. Because alcohol abuse independently increases the incidence of acute ...respiratory distress syndrome in at-risk individuals, we hypothesized that donor alcohol use is correlated with an increased risk of PGD. As a pilot study, we collected alcohol use histories using a validated instrument, the Alcohol Use Disorder Identification Test questionnaire, from 74 donors and correlated these with the development of PGD in corresponding recipients. Nineteen percent (14/74) of donors were classified as heavy alcohol users, as defined by the Alcohol Use Disorder Identification Test scores ≥8. In the 1st 4 days posttransplantation, similar percentages of recipients developed grade 3 PGD on at least 1 day (heavy alcohol user = 29% 4/14 versus lighter alcohol user = 27% 16/60); however, recipients receiving a lung from a heavy alcohol user were more likely to have multiple and consecutive days of grade 3 PGD, especially in the 1st 48 hours post-transplant. Both median length of stay in the intensive care unit and hospital were somewhat longer in the heavy alcohol user group (9 versus 7 days and 19.5 versus 17.5 days, respectively). If these preliminary findings are validated in a multi-center study, they would have important implications not only for our understanding of the pathophysiology of PGD but also for the development of novel treatments based on the evolving evidence from experimental and clinical studies on how alcohol abuse renders the lung susceptible to acute edematous injury.
Highly sensitized patients, who are often black and Hispanic women, are less likely to be listed for lung transplant and are at higher risk for prolonged waitlist time and waitlist death. In this ...review, the authors discuss strategies for improving access to transplant in this population, including risk stratification of crossing pretransplant donor-specific antibodies, based on antibody characteristics. The authors also review institutional protocols, such as perioperative desensitization, for tailoring transplant immunosuppression in the highly sensitized population. The authors conclude with suggestions for future research, including development of novel donor-specific antibody-directed therapeutics.
1 Atlanta Veterans Affairs Medical Center Pulmonary Section, Decatur 30033; and 2 Division of Pulmonary, Allergy, and Critical Care Medicine and 3 Department of Pediatrics, Emory University School of ...Medicine, Atlanta, Georgia 30322
Submitted 14 May 2003
; accepted in final form 15 September 2003
Chronic alcohol abuse increases the risk of developing acute lung injury approximately threefold in septic patients, and ethanol ingestion for 6 wk in rats impairs alveolar epithelial barrier function both in vitro and in vivo. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a trophic factor for the alveolar epithelium, and a recent phase II clinical study suggests that GM-CSF therapy decreases sepsis-mediated lung injury. Therefore, we hypothesized that GM-CSF treatment could improve ethanol-mediated defects in the alveolar epithelium during acute stresses such as endotoxemia. In this study, we determined that recombinant rat GM-CSF improved lung liquid clearance (as reflected by lung tissue wet:dry ratios) in ethanol-fed rats anesthetized and then challenged with 2 ml of saline via a tracheostomy tube. Furthermore, GM-CSF treatment improved lung liquid clearance and decreased epithelial protein leak in both control-fed and ethanol-fed rats after 6 h of endotoxemia induced by Salmonella typhimurium lipopolysaccharide given intraperitoneally, but with the greater net effect seen in the ethanol-fed rats. Our previous studies indicate that chronic ethanol ingestion decreases lung liquid clearance by increasing intercellular permeability. Consistent with this, GM-CSF treatment in vitro decreased permeability of alveolar epithelial monolayers derived from both control-fed and ethanol-fed rats. As in the endotoxemia model in vivo, the effect of GM-CSF was most dramatic in the ethanol group. Together, these results indicate that GM-CSF treatment has previously unrecognized effects in promoting alveolar epithelial barrier integrity and that these salutary effects may be particularly relevant in the setting of chronic alcohol abuse.
acute respiratory distress syndrome; glutathione; epithelium; surfactant; sepsis
Address for reprint requests and other correspondence: D. M. Guidot, Atlanta VAMC (151-P), 1670 Clairmont Road, Decatur, GA 30033 (E-mail: dguidot{at}emory.edu ).
Lung transplant (LT) recipients often receive dapsone for Pneumocystis jirovecii pneumonia (PCP) prophylaxis. However, the prevalence of dapsone-induced hematologic toxicity in LT recipients is ...unknown. We report a high prevalence of hemolytic anemia (HA) associated with dapsone use in LT patients when compared with other patients described in the literature who have been prescribed dapsone prophylaxis.
We performed a retrospective chart review on all LT recipients who received dapsone prophylaxis between 2004 and 2006. Demographics, ideal body weight (IBW), severity of anemia, transfusion requirements, laboratory evidence of hemolysis, serum creatinine and glucose-6-phosphate deyhdrogenase (G6PD) enzyme levels were collected.
Forty-three patients received dapsone. Ten (22.7%) patients had HA, despite normal G6PD levels. The mean drop in hemoglobin from baseline was 2.7 g/dl (95% confidence interval CI 1.9 to 3.5, p < 0.0001). Of those patients with HA, 6 had elevated serum creatinine from baseline. The odds ratio for hemolysis was 4.75 for each 1.0-mg/dl increase in creatinine (95% CI 1.07 to 21.03, p = 0.04). Mean IBW for the HA group was 58.4 kg. A dapsone dose of 100 mg/day orally resulted in a mean dose of 1.7 mg/kg.
The prevalence of dapsone-induced HA in LT recipients is 5-fold higher than the reported rate in the population of human immunodeficiency virus (HIV) patients. Individuals with renal failure or low body weight and for whom dose exceeds 1.5 mg/kg may be at increased risk for dapsone-induced HA. Although current CDC guidelines do not recommend adjusting dose by IBW or renal function, we suggest that consideration should be given to these dosing strategies.
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