Lung Transplantation For Pulmonary Fibrosis Research Articles

(891) - Predicted Total Lung Capacity is a Reliable Size-Matching Parameter in Lung Transplantation for Pulmonary Fibrosis

(891) - Predicted Total Lung Capacity is a Reliable Size-Matching Parameter in Lung Transplantation for Pulmonary Fibrosis

DYSKERATOSIS CONGENITA: A RARE CAUSE OF USUAL INTERSTITIAL PNEUMONIA

DYSKERATOSIS CONGENITA: A RARE CAUSE OF USUAL INTERSTITIAL PNEUMONIA

Single Lung Transplantation for Pulmonary Fibrosis Secondary to COVID-19

IntroductionAs of April 2021, 78 lung transplants (LTx) were performed for a diagnosis of COVID-19: 50 for COVID-19 ARDS and 28 for pulmonary fibrosis. Bilateral LTx has been recommended as many patients develop significant pulmonary hypertension. Additionally, native lung explants may include cavitary areas of pneumonia, which could serve as a nidus for infection. Single LTx (SLTx) can be considered in patients who have chronic pulmonary fibrosis secondary to COVID-19 with a short window to receive a transplant, or who would otherwise be considered for a single lung. There have been no published cases of a single lung transplant for COVID-19 pulmonary fibrosis. We present a case of a patient with pulmonary fibrosis from COVID-19 who underwent SLTx.Case ReportA 70yo male with O+ blood type was hospitalized 8/2020 to 10/2020 with COVID-19 pneumonia, treated with Remdesivir and Tocilizumab. He had hypoxia but never required intubation. His course was complicated by bilateral pneumothoraces requiring chest tubes. He developed pulmonary fibrosis requiring 6 L of oxygen at rest. CT scan of his chest showed multifocal, peripheral prominent ground glass opacities and interlobal septal thickening with traction bronchiectasis. Ventilation-perfusion scan demonstrated 22% perfusion to the left lung and 78% to the right lung. Right heart catheterization showed pulmonary artery pressures of 36/12 mmHg. His pulmonary function test was suggestive of restrictive disease (FEV 0.81 L [30%], FVC 0.96 L [27%], and FEV1/FVC 85%) that had worsened over time. He was presented at multidisciplinary review board with recommendation to list for left SLTx, which was activated August 2021. The patient was admitted in September 2021 and underwent left single lung transplant via left anterolateral thoracotomy, off cardiopulmonary bypass. Total ischemia time was 3:54. Explant pathology showed end stage pulmonary fibrosis. The patient was extubated on postoperative day 1 with an uneventful postoperative course. He was discharged to skilled nursing facility on postoperative day 26 for rehabilitation.SummarySLTxp is safe and feasible for COVID-19 related pulmonary fibrosis in well-selected patients who have a short window to receive a transplant.

Lung Transplantation for Pulmonary Fibrosis Associated With Hermansky-Pudlak Syndrome. A Single-center Experience.

Background.Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage defect with resultant bleeding diathesis, and pulmonary fibrosis. The bleeding diathesis associated with HPS had long been considered a contraindication to lung transplantation; consequently, few reports of successful lung transplantation for HPS exist.Methods.In the largest case series on lung transplant for HPS, we describe the characteristics of 11 lung transplant candidates with HPS-related pulmonary fibrosis, and the management and outcomes of 7 patients who underwent lung transplantation.Results.Of the 7 patients transplanted, 30-d survival was 85.7% (6/7). Six patients had at least 2 y of follow-up available with a 1-y survival of 83.3% and a 2-y survival of 83.3% (5/6). The median age at referral was 48 y (range 29–62 y). Eight patients (72.7%) were of Puerto Rican ancestry with confirmed type 1 HPS mutation. Six out of 7 patients received prophylaxis for bleeding diathesis, with a majority receiving desmopressin; 1 patient was administered aminocaproic acid infusion, and another received 2 units of platelets before surgery. Estimated blood loss and the amount of intraoperative blood product administered was highly variable with or without prophylaxis. Median blood loss was 400 mL (range 125–750) and estimated blood products administered was 700 mL (range 490–4043).Conclusions.HPS should not be considered a contraindication for lung transplantation. Although patients with HPS seem to have an increased risk of massive hemorrhage, the risk is unpredictable. Transplant teams should prepare a preoperative plan in consultation with hematology and consider the use of prophylactic platelet transfusion and desmopressin.

Acute worsening of native lung fibrosis after single lung transplantation for pulmonary fibrosis: two case reports

BackgroundIn patients receiving single lung transplantation for idiopathic pulmonary fibrosis, worsening of fibrosis of the native lung is usually progressive over time, with no significant effects on gas exchange.Case presentationHere, we describe the cases of two Caucasian male recipients of single lung transplants for idiopathic pulmonary fibrosis, 65 and 62 years of age, who exhibited acute worsening of lung fibrosis after an episode of serious viral infection (cytomegalovirus primo-infection in one case and COVID-19 in the other). In both cases, along with opacification of the native lung over several days, the patients presented acute respiratory failure that required the use of high-flow nasal oxygen therapy. Eventually, hypoxemic respiratory failure resolved, but with rapid progression of fibrosis of the native lung.ConclusionWe conclude that acute worsening of fibrosis on the native lung secondary to a severe viral infection should be added to the list of potential complications developing on the native lung after single lung transplantation for idiopathic pulmonary fibrosis.

First Successful Lung Transplantation for Pulmonary Fibrosis Due to Severe COVID-19 Infection in the US

IntroductionLung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19 acute respiratory distress syndrome. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung. Here, we report the first successful lung transplantation in a patient with non-resolving COVID-19 associated acute respiratory distress syndrome in the United States.Case ReportThe recipient was a 28-year old female with past medical history of neuromyelitis optica treated with mycophenolate and rituximab who developed COVID pneumonia leading acute respiratory distress syndrome. The patient was intubated for 8 days with prone prior to initiation of VV ECMO. Her ECMO course was complicated by right sided pneumothorax requiring multiple pleural tubes and the development of Serratia marcescens pneumonia with left lower lung necrosis, and a liver capsular bleed necessitating emergent exploratory laparotomy. (Figure1a, b) She received antibiotics, remdesivir, hydroxychloroquine, tocilizumab, and convalescent plasma. However there was no signs of recovery and she was listed for lung transplantation after ECMO support for 32 days . Implantation was supported with central VA ECMO, and there was severe dense vascular adhesions bilaterally with severe distortion of hilar. (Figure1c) Explanted Lungs damaged by COVID-19 were free of virus but pathology showed extensive evidence of acute interstitial inflammation with fibrosis which consistence with end-stage pulmonary fibrosis. (Figure1d, e) The patient was decannulated from VV ECMO on POD 17, and was discharged on POD 27. (Figure1f) Four months after transplantation, she is at home with oxygen saturations above 98% on room air.SummaryOur experience suggest that lung transplant is the only option for survival for some patients with severe COVID-19 develop fibrotic lung.

Intraoperative Extracorporeal Circulatory Support in Lung Transplantation for Pulmonary Fibrosis

Venous-arterial extracorporeal membrane oxygenation (ECMO) is an established technique for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Patients with pulmonary fibrosis have a higher risk to require it. The aim of this study was to identify risk factors for the need of intraoperative ECMO use. Records of patients undergoing lung transplantation for pulmonary fibrosis at our institution between January 2010 and May 2018 were retrospectively reviewed. Univariate logistic regression analysis was used for statistical identification of risk factors. There were 105 patients (34%) who required intraoperative ECMO support (ECMO+ group), and 203 (66%) did not (ECMO- group). Preoperative proof of pulmonary hypertension was identified as a risk factor for intraoperative ECMO support (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.2-6.5; P < .01). Revealed mean pulmonary arterial pressure values exceeding 50 mm Hg and pulmonary vascular resistance values exceeding 9.4 Wood units were identified as risk factors for the need of intraoperative ECMO use with a prediction probability of 70%. Increased recipient body surface area (OR, 0.2; 95% CI, 0.1-0.5; P < .01) emerged as a protective factor against intraoperative ECMO (Hosmer-Lemeshow statistic, P= .71) as well as higher cardiac output (OR, 0.7; 95% CI, 0.6-0.9; P < .01). The postoperative course was more complicated in the ECMO+ group, whereas survival at 5 years did not differ among groups (70% vs 69%, P= .79). Pulmonary hypertension with elevated pulmonary vascular resistance values predicts the need of intraoperative ECMO in patients receiving lung transplantation for pulmonary fibrosis. Although the postoperative course was more complicated in the ECMO+ group, long-term survival did not differ significantly.

Effect of pirfenidone on wound healing in lung transplant patients

Background: The drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period. Methods: We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. Results: We describe 18 patients who took pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone for at least 30 days; nine patients had been on pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. Conclusions: In our experience, pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with pirfenidone before lung transplantation.

Bigger is Better - Oversizing May Improve Survival in Single Lung Transplantation for Pulmonary Fibrosis

Purpose The donor to recipient predicted total lung capacity (pTLC) ratio is routinely used to guide size matching. Guidelines do not differentiate between underlying diseases. We aimed to assess if post-transplant outcomes for pulmonary fibrosis (PF) single lung transplant recipients is improved when receiving an oversized lung. Methods Data on all adult patients who received a first single or bilateral lung-only transplant in the UK between 2007 and 2016 were obtained from the UK Transplant Registry. Donor to recipient pTLC mismatch ratio was used to assign patients to three groups: 0%. Post-transplant survival was assessed using Kaplan-Meier survival curves and log-rank tests. The pTLC mismatch ratio was further analysed as a continuous non-linear variable using an unadjusted Cox Proportional Hazards Regression model. A natural cubic spline was used to represent non-linearity, enabling cubic expressions between “knots” at the 5%, 35%, 65% and 95% percentiles. Results 321 patients were included in our cohort; 243 (75.7%) were male, mean age of 56 years. Mean donor pTLC was 5.7L, mean recipient pTLC was 6.4L, mean pTLC mismatch ratio was -10.1%. Kaplan-Meier analysis suggested no significant difference between the mismatch categories upon 90 day (p=0.28) or 1 year (p=0.16) post-transplant survival, with borderline significance 5 years post-transplant (p=0.08). No significant differences were found analysing the bilateral lung transplant cohort alone. Analysis of single lung recipients showed borderline significance at 1 year (p=0.07) and significant difference 5 years post-transplant (p=0.05). An unadjusted Cox Regression model was therefore applied to single lung transplant recipients only, demonstrating a significant non-linear effect of the pTLC mismatch ratio at 90 days and borderline effect at 1 year and 5 years post transplant (p=0.05, p=0.09 and p=0.06, respectively). The non-linear effect detected for 90 day post-transplant survival was such that the hazard of death decreases the larger the mismatch, until approximately +/-20%. A similar effect was detected for 1 year and 5 years post-transplant, but to a lesser extent. Conclusion Oversizing donor lung allografts in patients receiving a single lung transplant for pulmonary fibrosis may improve survival in both the short and long term.

Need for and Outcomes of Intraoperative Extracorporeal Circulatory Support in Lung Transplantation for Pulmonary Fibrosis

Purpose V-a extracorporeal membrane oxygenation (ECMO) has been successfully used for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Especially patients with lung fibrosis are at risk to require intraoperative v-a ECMO. Aim of this study was to identify predisposing risk factors for intraoperative ECMO support and postoperative outcomes in this cohort of patients. Methods Patients transplanted for lung fibrosis between January 2010 and May 2018 were included into the study. Patients transplanted on v-a ECMO formed group A, the remaining, group B. Follow-up amounted to a mean of 37±27 months. Multivariate forward and backward logistic regression analysis was used to identify risk factors for ECMO. Results Among the 1042 lung-transplanted patients, 313 (30%) patients underwent bilateral transplantation for lung fibrosis. Five patients were excluded as they received conventional cardiopulmonary support due to different resaons. Among the remaining 308 patients, 109 (35%) patients formed group A, 199 (65%), group B. Presence of pulmonary hypertension (OR 3.1; 95%CI 1.8-5.3, p Conclusion Smaller recipient BSA, pulmonary hypertension with high PVR values and evidence of a dilated and hypertrophic right ventricle can predict the need for intraoperative ECMO in patients transplanted for lung fibrosis. Although the postoperative course was more complicated in group A than B, long-term survival did not differ between groups.

Effect of pirfenidone on wound healing in lung transplant patients

BackgroundThe drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period.MethodsWe retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015.ResultsWe describe 18 patients who took pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone for at least 30 days; nine patients had been on pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar.ConclusionsIn our experience, pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with pirfenidone before lung transplantation.

Size Matters in Single Lung Transplantation for Pulmonary Fibrosis!

Size Matters in Single Lung Transplantation for Pulmonary Fibrosis!

(117) - Risk Factors for Intraoperative Extracorporeal Circulatory Support in Patients Undergoing Lung Transplantation for Pulmonary Fibrosis

(117) - Risk Factors for Intraoperative Extracorporeal Circulatory Support in Patients Undergoing Lung Transplantation for Pulmonary Fibrosis

Successful Catheter Ablation of Right Atrial Tachycardia After Bilateral Lung Transplantation

A 47-year-old woman underwent bilateral lung transplantation for pulmonary fibrosis in June of 2013. The early postoperative period was complicated by continuous atrial arrhythmias that proved unresponsive to antiarrhythmic agents (propafenon and bisoprolol). Therefore, in February 2014, we performed an electrophysiological study after adequate antibiotic and antimycotic prophylaxis. During the procedure, the clinical tachycardia was easily inducible with burst atrial pacing and programmed atrial extrastimuli. Tachycardia cycle length varied between 380 ms and 420 ms, and A-A-V response after ventricular burst pacing suggested atrial tachycardia. Entrainment mapping from the area of early activation failed to demonstrate reentry as the underlying mechanism of the tachycardia, thus ectopic atrial tachycardia was diagnosed. Electroanatomical mapping was performed with ENSITE NavX system (Endocardial Solutions Inc.) during ongoing arrhythmia (Figure ​(Figure1).1). Activation map showed that earliest activation was in the right atrium, corresponding to a scar of the extracorporeal membrane oxigenator (ECMO) cannula during lung transplantation. To avoid paralysis of the diaphragm, we paced the high right atrial region with high energy to demonstrate and mark the location of right phrenic nerve. Subsequently, we performed RF ablation with 3.5 mm irrigated tip catheter (AlCath Flux Blue G eXtra) using 40 W energy and 43°C temperature limit. After the application of one RF ablation at the site of earliest activation (ablation time 46 seconds), the arrhythmia stopped immediately and was no longer inducible even after administration of isoproterenol. The total procedure time was 75 minutes with a fluoroscopy time of 2.3 minutes. No procedural complications occurred. Outpatient visits and 24-hour Holter electrocardiogram monitoring were scheduled every 3 months. The patient was free of symptoms and arrhythmia episodes without any antiarrhythmic medication during the 9-month follow-up period. FIGURE 1 Left side: 12 lead surface electrocardiogram (paper speed 100 mm/sec) and intracardiac electrocardiogram (ablation catheter and coronary sinus catheter) during ongoing arrhythmia. Cycle length is changing from beat to beat. The local activation recorded ... Atrial tachyarrhythmias are frequent after lung transplantation but the incidence of right atrial tachycardia is very low. Most commonly atrial fibrillation is observed in the early postoperative period and left atrial tachycardia occurs later in time.1-4 Right atrial tachycardia might also be associated to the operation, during which an ECMO is implanted with cannulation of the right atrium and aorta. Damaging the anterior part of the high right atrium during this step might be the ground of arrhythmia substrate formation. To the best of our knowledge, our case represents the first successful ablation of right atrial tachycardia after lung transplantation due to scarring of a passagere cannula of ECMO. Ablation of typical right atrial flutter and left atrial tachycardias originating from the donor pulmonary veins has been reported previously.1-4 Atrial ablation in lung transplant recipients is rarely performed, in contrast to heart transplant recipients, where ablation of atrial arrhythmias has repeatedly been reported and arrhythmias are dominantly originating from the right atrium.5

Severe hematologic complications after lung transplantation in patients with telomerase complex mutations

Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations. Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases. There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59-1,709 days). Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.

FRI0478 Update on Lung Transplantation in Systemic Sclerosis in Spain

BackgroundLung transplantation (LT) has been proposed as a treatment for advanced Interstitial Lung Disease (ILD) and/or Pulmonary Arterial Hypertension (PAH) associated to Systemic Sclerosis (SSc). Few studies are available and...

Preoperative pulmonary artery pressure and mortality after lung transplantation

The purpose of this study was to determine the influence of changes in pulmonary artery pressure during the waiting period on survival after lung transplantation for pulmonary fibrosis. We identified 65 patients with pulmonary fibrosis who underwent lung transplantation from 2003 to 2010. Pulmonary artery pressure determined at listing was compared with intraoperative pressure. The primary outcome was overall survival. Co-variates included type of transplantation (single or bilateral), ischemic time, recipient and donor age and sex. The median age of the 65 patients undergoing transplantation was 58 years, and 27 (43%) underwent bilateral sequential transplantation. Twenty-two (35%) patients presented at transplantation with a mean pulmonary artery pressure increased by at least 10% compared to the initial pressure at the time of listing. Rising pulmonary artery pressure at transplantation was associated with increased mortality (p = 0.022). Other factors including type of operation, ischemic time, age, and sex, were not significantly associated with mortality. Post-transplantation survival was worse among recipients who had pulmonary artery pressure increased by at least 10% at transplantation (p = 0.003, logrank). Increasing pulmonary artery pressure while awaiting lung transplantation is associated with worse long-term survival following transplantation, and is a sign of progressively worsening disease for which greater urgency of donor organ allocation should be considered.

711 Changes in Pulmonary Volumes in Patients Who Underwent Lung Transplantation for Pulmonary Fibrosis

711 Changes in Pulmonary Volumes in Patients Who Underwent Lung Transplantation for Pulmonary Fibrosis

698 Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation in Pulmonary Fibrosis

698 Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation in Pulmonary Fibrosis

Exacerbation of Pulmonary Fibrosis Following Single Lung Transplantation

Acute exacerbations of interstitial lung disease present as clinical deteriorations, with progressive hypoxemia and parenchymal consolidation not related to infection, heart failure or thromboembolic disease. Following single lung transplantation, patients receive maintenance immunosuppression, which could mitigate the development of acute exacerbations in the native lung. A 66-year-old man with fibrotic, nonspecific interstitial pneumonitis presented with fever, hypoxemia and parenchymal consolidation limited to the native lung four years after single lung transplantation. Investigations were negative for infection, heart failure and thromboembolic disease. The patient worsened over the course of one week despite broad-spectrum antimicrobial therapy, but subsequently improved promptly with augmentation of prednisone dosed to 50 mg daily and addition of N-acetylcysteine. Hence, the patient fulfilled the criteria for a diagnosis of an acute exacerbation of pulmonary fibrosis in his native lung. Clinicians should consider acute exacerbation of parenchymal lung disease of the native lung in the differential diagnosis of progressive respiratory deterioration following single lung transplantation for pulmonary fibrosis.