Living‐donor single‐lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins

This is a case report of a successful single‐lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6‐year‐old boy underwent living‐donor single‐lobe transplantation with the right lower lobe from his 31‐year‐old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO₂/FiO₂ in the intensive‐care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT‐guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.     

Surgical considerations in infant lung transplantation: Challenges and opportunities

Lung transplantation is a crucial component in the treatment of end-stage lung disease in infants. Traditionally, most lung transplants have been performed in older children and adults, resulting in a scarcity of data for infant patients. To address the challenges unique to this age group, novel strategies to provide the best preoperative, intraoperative, and postoperative care for these youngest patients are paramount. We review recent advances in bridge-to-transplantation therapy, including the use of a paracorporeal lung assist device, and differences in surgical technique, including bronchial artery revascularization, for incorporation into the overarching treatment strategy for infants undergoing lung transplantation.     

Spontaneous diaphragmatic rupture as a complication following lung transplantation

Spontaneous diaphragm rupture is a rare but potentially life‐threatening condition, requiring urgent surgical intervention. Here we present two patients who developed spontaneous right hemidiaphragm rupture with abdominal visceral herniation into the thoracic cavity several days following bilateral lung transplantation, as an unusual complication. Both patients' surgeries were performed through bilateral anterior thoracotomies and were uneventful. There may be an association with this complication and patients suffering with emphysema, typically receiving donor lungs smaller than their native lungs, and with significant pretransplant exposure to steroids, factors that when combined may contribute to an increased risk of spontaneous diaphragmatic rupture in the absence of a significant precipitant. If a similar clinical picture is seen, teams managing lung transplant recipients should be aware of this potential complication and recognize the need for urgent intervention.     

Single lung transplantation from a donor 8 months after double lung transplantation

Scarcity of donors leads transplant surgeons to consider extended‐criteria lungs and occasionally to accept the unlikely. Here we report a case of successful single lung transplantation from a donor 8 months after double lung transplantation.     

Simultaneous pancreas and kidney transplant after bilateral lung transplant for a recipient with cystic fibrosis

Cystic fibrosis (CF) is an inherited autosomal recessive disorder. Despite optimized therapy, the majority of affected individuals ultimately die of respiratory failure. Lung transplantation is the only available therapy that deals definitively with the end-stage pulmonary disease and has become the treatment of choice for some of these patients. As patients with CF are living longer, extrapulmonary manifestations may develop including pancreatic failure, which manifests as exocrine insufficiency and CF-related diabetes (CFRD). Both of these can be managed through pancreas transplantation. We have previously reported our series of three simultaneous lung and pancreas transplants in patients with CF, which were complicated by surgical issues for both the thoracic and abdominal portions, rejection and resistant infections with disappointing long-term survival. Based on these results, a sequential approach was adopted: first, the thoracic transplant; and second, once the patient has recovered, the abdominal transplants. This is the first reported case of pancreas and kidney transplantation performed after a lung transplant in a patient with CF. It demonstrates a successful approach to treating CF with a lung transplant, and in an effort to improve the patient's long-term outcome, treating CFRD and pancreatic enzyme insufficiency, with a subsequent pancreas transplant.     

Bilateral lung transplantation during pregnancy after ECMO for influenza-A caused ARDS

Pregnant women with influenza-A have an increased risk of developing acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can be used as salvage therapy, with lung transplantation as a therapeutic option. However, successful bilateral lung transplantation during pregnancy has never been reported before. We herein report the case of a 34-year-old primipara, who was diagnosed with ARDS caused by influenza-A-induced pneumonia at early gestation. After considering all possible therapeutic options and being fully dependent on VV-ECMO support, she underwent bilateral lung transplantation. The transplantation with intraoperative central VA-ECMO support was successfully performed with good recovery after an initial primary graft dysfunction. The pregnancy was prolonged until 29⁺⁵ gestational weeks. The newborn exhibited growth retardation and was initially stabilized, but later died due to severe, hypoxic respiratory failure and pulmonary hypertension. In conclusion, lung transplantation is a possible salvage therapy for patients with severe lung failure following ARDS during pregnancy. However, it places the mother and unborn child at risk. A multi-professional approach is warranted to diagnose and treat complications at an early stage.     

Lung donation following SARS-CoV-2 infection

There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and “efficacy” of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.     

Pediatric living donor liver transplantation with large‐for‐size left lateral segment grafts

Usage of “large‐for‐size” left lateral segment (LLS) liver grafts in children with high graft to recipient weight ratio (GRWR) is controversial due to concerns about increased recipient complications. During the study period, 77 pediatric living donor liver transplantations (LDLTs) with LLS grafts were performed. We compared recipients with GRWR ≥2.5% (GR‐High = 50) vs GRWR <2.5% (GR‐Low = 27). Median age was higher in the GR‐Low group (40 vs 8 months, P> .0001). Graft (GR‐High: 98%, 98%, 98% vs GR‐Low: 96%, 93%, 93%) and patient (GR‐High: 98%, 98%, 98% vs GR‐Low: 100%, 96%, 96%) survival at 1, 3, and 5 years was similar between groups (P = NS). Overall complications were also similar (34% vs 30%; P = .8). Hepatic artery and portal vein thrombosis following transplantation was not different (P = NS). Delayed abdominal fascia closure was more common in GR‐High patients (17 vs 1; P = .002). Subgroup analysis comparing recipients with GRWR ≥4% (GR‐XL = 20) to GRWR <2.5% (GRWR‐Low = 27) revealed that delayed abdominal fascia closure was more common in the GR‐XL group, but postoperative complications and graft and patient survival were similar. We conclude that pediatric LDLT with large‐for‐size LLS grafts is associated with excellent clinical outcomes. There is an increased need for delayed abdominal closure with no compromise of long‐term outcomes. The use of high GRWR expands the donor pool and improves timely access to the benefits of transplantation without extra risks.     

Sleep-disordered breathing after lung transplantation: An observational cohort study

Data concerning sleep-disordered breathing (SDB) after lung transplantation (LTX) are scarce. This study aims to analyze prevalence, associated factors, and impact on survival of moderate to severe SDB in a large cohort of consecutive LTX patients (n = 219). Patients underwent a diagnostic polysomnography 1 year after LTX. Moderate to severe SDB was present in 57.5% of patients, with the highest prevalence in chronic obstructive pulmonary disease/emphysema (71.1%) and pulmonary fibrosis (65.1%). SDB patients were older, mostly male, and had higher body mass index and neck circumference. Nocturnal diastolic and 24-hour blood pressures were higher in SDB patients. In 45 patients, polysomnography was also performed pre-LTX. Compared to pre-LTX, mean apnea/hypopnea index (AHI) increased significantly after LTX. A significant correlation was seen between lung function parameters and AHI, suggesting a role of decreased caudal traction on the pharynx. Presence of SDB had no impact on mortality or prevalence of chronic lung allograft dysfunction. However, survival was better in continuous positive airway pressure (CPAP) compliant SDB patients compared to SDB patients without CPAP treatment. These findings may be pertinent for systematic screening of SDB after LTX.     

Immunity to varicella,measles, and mumps in patients evaluated for lung transplantation

Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in post-transplant patients on immunosuppression regimens. Therefore, we studied rates of immunity against vaccine-preventable viruses in lung transplantation (LTx) candidates and their associations with underlying lung disease and clinical characteristics. We retrospectively studied 1025 consecutive adult patients who underwent first-time evaluation for LTx at a single center between January 2016 and October 2018. Viruses studied included varicella zoster (VZV), measles, and mumps. Young age (17–48 years old) was negatively associated with immunity for VZV (OR 4.54, p < .001), measles (OR 15.45, p < .001) and mumps (OR 3.1, p < .001), as compared to those 65+. Many LTx candidates with cystic fibrosis (CF) had undetectable virus-specific antibody titers including: 13.5% for VZV, 19.1% for measles, and 15.7% for mumps with significant odds of undetectable titers for VZV (OR 4.54, p < .001) and measles (OR 2.32, p = .010) as compared to those without CF. Therefore, a substantial number of patients undergoing LTx evaluation had undetectable virus-specific antibody titers. Our results emphasize the importance of screening for immunity to vaccine-preventable infections in this population and the need for revaccination in selected patients to boost their humoral immunity prior to transplantation.

     

Parenteral administration of oral medications in lung transplant recipients: An underrecognized problem

Microcrystalline cellulose (MCC) is an insoluble material commonly used as a binder and filler in oral medications. Identification of pulmonary intravascular deposition of MCC in transbronchial biopsies from lung transplant (LT) recipients following parenteral injection of oral medications has only been reported once. A search of our surgical pathology electronic database was performed from January 1, 2000 to November 1, 2017 using the text “transplant transbronchial.” The diagnosis field for all cases retrieved was then searched for the text “cellulose.” These cases were queried for patient demographics and outcomes. Between January 1, 2000 and November 1, 2017, 1558 lung transplants were performed in 1476 individual patients at our institution; 12 were identified to have MCC in their lung tissue. Patients with MCC identified on biopsies were more likely to be transplanted for cystic fibrosis versus other indications and younger versus older. MCC identified in 2 of our cases was favored to be donor derived. Of the 12 patients, 6 (50%) are deceased. MCC within the pulmonary vasculature may be an indicator of increased complications, mortality, or shortened survival in LT recipients. Detecting intravascular MCC and distinguishing it from aspirated foreign material can be challenging. Awareness of the differential diagnosis for pulmonary foreign material is of paramount importance for the pathologist.     

Impact of kidney transplantation on sleep apnea severity: A prospective polysomnographic study

Fluid overload has been associated with a high prevalence of sleep apnea (SA) in patients with end‐stage kidney disease (ESKD). In this prospective study, we hypothesized that improvement in kidney function and hydration status after kidney transplantation (Tx) may result in an improvement in SA severity. A total of 196 patients on the kidney Tx waiting list were screened for SA using home nocturnal polysomnography (PSG) to measure the apnea‐hypopnea index (AHI) and underwent bioimpedance to assess body composition. Of 88 participants (44.9%) with SA (AHI ≥ 15/h), 42 were reassessed 6 months post‐Tx and were compared with 27 control patients. There was a significant, but small, post‐Tx improvement in AHI (from 44.2 ± 24.3 to 34.7 ± 20.9/h, P = .02) that significantly correlated with a reduction in fluid overload (from 1.8 ± 2.0 to 1.2 ± 1.2 L, P = .02) and body water (from 54.9% to 51.6%, P = .003). A post‐Tx increase in body fat mass (from 26% to 30%, P = .003) possibly blunted the beneficial impact of kidney Tx on SA. All parameters remained unchanged in the control group. In conclusion, SA is a frequent condition in ESKD patients and partially improved by kidney Tx. We suggest that SA should be systematically assessed before and after kidney Tx. ClinicalTrials.gov Identifier: NCT02020642.     

Transplantation for pulmonary arterial hypertension with congenital heart disease: Impact on outcomes of the current therapeutic approach including a high-priority allocation program

Patients with end-stage pulmonary arterial hypertension due to congenital heart disease have limited access to heart-lung transplantation or double-lung transplantation. We aimed to assess the effects of a high-priority allocation program established in France in 2007. We conducted a retrospective study to compare waitlist and posttransplantation outcomes before versus after implementation of the high-priority allocation program. We included 67 consecutive patients (mean age at listing, 33.2 ± 10.5 years) with pulmonary arterial hypertension due to congenital heart disease listed for heart-lung transplantation or double-lung transplantation from 1997 to 2016. At one month, the incidences of transplantation and death before transplantation were 3.5% and 24.6% in 1997–2006, 4.8% and 4.9% for patients on the regular list in 2007–2016, and 41.2% and 7.4% for patients listed under the high-priority allocation program (p < .001 and p = .0001, respectively). Overall survival was higher in patients listed in 2007–2016 (84.2% and 61.2% at 1 and 10 years vs. 36.8% and 22.1%, p = .0001). Increased incidence of transplantation, decreased waiting list mortality, and improved early and long-term outcomes were observed in patients with pulmonary arterial hypertension due to congenital heart disease listed for transplantation in the recent era, characterized by implementation of a high-priority allocation program.     

Frailty phenotypes and mortality after lung transplantation: A prospective cohort study

Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score–adjusted Cox models. We calculated postestimation marginalized standardized risks for 1‐year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1‐ and 4‐year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6‐36.0 and aHR 3.8; 95%CI: 1.8‐8.0, respectively). Each 1‐point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08‐1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%‐21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1‐13.2) but not over longer follow‐up. Preoperative frailty is associated with an increased risk of death after lung transplantation.     

The role of C4d deposition in the diagnosis of antibody‐mediated rejection after lung transplantation

Antibody‐mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single‐center study to characterize cases of C4d‐negative probable AMR and to compare these to cases of definite (C4d‐positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d‐positive and 45 (62%) were C4d‐negative. The two groups had a similar clinical presentation, and although more patients in the C4d‐positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody‐depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR.     

Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation

Acute kidney injury (AKI) is common after lung transplantation, but molecular markers remain poorly studied. The endothelial activation markers soluble thrombomodulin (sTM), protein C, and plasminogen activator inhibitor‐1 (PAI‐1) are implicated in kidney microcirculatory injury in animal models of AKI. We tested the association of 6‐hour postreperfusion plasma levels of these markers with posttransplant AKI severity in patients enrolled in the Lung Transplant Outcomes Group prospective cohort study at the University of Pennsylvania during two eras: 2004‐06 (n = 61) and 2013‐15 (n = 67). We defined AKI stage through postoperative day 5 using Kidney Disease Improving Global Outcomes creatinine criteria. We used multivariable ordinal logistic regression to determine the association of each biomarker with AKI, adjusted for primary graft dysfunction and extracorporeal life support. AKI occurred in 57 (45%) patients across both eras: 28 (22%) stage 1, 29 (23%) stage 2‐3. Higher sTM and lower protein C plasma levels were associated with AKI stage in each era and remained so in multivariable models utilizing both eras (sTM: OR 1.76 [95% CI 1.19‐2.60] per standard deviation, P = .005; protein C: OR 0.54 [1.19‐2.60], P = .003). We conclude that 6‐hour postreperfusion plasma sTM and protein C levels are associated with early postlung transplant AKI severity.     

Pulmonary malakoplakia secondary to Rhodococcus equi infection mimicking a lung neoplasm in a lung transplant recipient

Pulmonary masses occasionally occur after lung transplantation and vary in etiology, which includes malignant and benign conditions, such as infection. Here, we report a case of a patient presenting with a lung mass 3 years after lung transplant. To our knowledge, this is the first described case of pulmonary malakoplakia due to Rhodococcus equi infection in an allograft post–lung transplantation. This case outlines the challenges of differentiating benign from malignant masses after transplantation.     

Multiple breath washout in pediatric patients after lung transplantation

Forced expiratory volume in 1 second (FEV₁) from spirometry is the most commonly used parameter to detect early allograft dysfunction after lung transplantation (LTx). There are concerns regarding its sensitivity. Nitrogen‐multiple breath washout (N₂‐MBW) is sensitive at detecting early global (lung clearance index [LCI]) and acinar (S_acin) airway inhomogeneity. We investigated whether N₂‐MBW indices indicate small airways pathology after LTx in children with stable spirometry. Thirty‐seven children without bronchiolitis obliterans syndrome [BOS] at a median of 1.6 (0.6‐3.0) years after LTx underwent N₂‐MBW and spirometry, 28 of those on 2 occasions (≤6 months apart) during clinically stable periods. Additional longitudinal data (11 and 8 measurements, respectively) are provided from 2 patients with BOS. In patients without BOS, LCI and S_acin were significantly elevated compared with healthy controls. LCI was abnormal at the 2 test occasions in 81% and 71% of patients, respectively, compared with 30% and 39% of patients with abnormal FEV₁/forced vital capacity (FVC). Correlations of LCI with FEV₁/FVC (r = 0.1, P = .4) and FEV₁ (r = ?0.1, P = .6) were poor. N₂‐MBW represents a sensitive and reproducible tool for the early detection of airways pathology in stable transplant recipients. Moreover, indices were highly elevated in both patients with BOS. Spirometry and LCI showed poor correlation, indicating distinct and complementary physiologic measures.