Outcomes of lung transplantation for chronic obstructive pulmonary disease.

Introduction: Chronic obstructive pulmonary disease is a progressive airway disease that can progress to the terminal stage requiring oxygen supply. In this period, lung volume reduction therapies and/or lung transplantation may be considered. Morbidity and mortality risks due to transplant surgery and posttransplant immunosuppressive therapy show the importance of selecting the best candidates who will benefit from transplantation. In this context, BODE index criteria serve as important markers. This study aimed to analyze the outcomes of lung transplantation in patients with chronic obstructive pulmonary disease and to identify variables that may affect post-transplant clinical outcomes. Materials and Methods: Lung transplants diagnosed with chronic obstructive pulmonary disease performed in our center between March 2013 and January 2023 were included in the study. Demographic information and both pre-op and post-op clinical data of the transplant patients were collected. The effect of BODE index criteria and other pre-transplant clinical data on short- and long-term outcomes after transplantation were investigated. Results: During the study period, 34 lung transplants were performed for chronic obstructive pulmonary disease. One patient died during the operation, three patients received single transplants, and 30 received double transplants. Post-operative primary graft dysfunction was more common in single transplant recipients. The results were comparable between single and double transplants in terms of post-transplant pulmonary function and the development of chronic lung allograft dysfunction. BODE index criteria had no effect on early and late post-operative clinical data, however intra-operative use of extracorporeal membrane oxygenation, primary graft dysfunction, and prolonged extubation were significantly higher in recipients younger than 60 years. Conclusion: Our study suggests that prelisting demographic and clinical data of chronic obstructive pulmonary disease patients had no significant effect on post-operative outcomes, however, intra-operative ECMO use, prolonged extubation, primary graft dysfunction (p< 0.05 for each) and chronic rejection (p> 0.05) were more common in patients who are <60 years of age. These data need to be confirmed by larger studies.

The Effect of Ideal/Standard Donor and Marginal Donor Use on Primary Graft Dysfunction After Lung Transplantation in Turkey.

OBJECTIVE: The transplantation waiting list is getting longer day by day with the spread of lung transplantation and awareness of it. However, the donor pool cannot keep up with this rate. Therefore, nonstandard (marginal) donors are widely used. By studying the lung donors presented at our center, we aimed to raise awareness of the donor shortage and compare clinical outcomes in recipients with standard and marginal donors. MATERIALS AND METHODS: The data from recipients and donors of lung transplants performed at our center between March 2013 and November 2022 were retrospectively reviewed and recorded. Transplants with ideal and standard donors were classified as group 1, and those with marginal donors were classified as group 2. Primary graft dysfunction rates, intensive care unit, and hospital stay days were compared. RESULTS: Eighty-nine lung transplants were performed. A total of 46 recipients were in group 1 and 43 were in group 2. There were no differences between groups in the development of stage 3 primary graft dysfunction. However, a significant difference was found in the marginal group for developing any stage primary graft dysfunction. Donors were mostly from the western and southern regions of the country and from the education and research hospitals. CONCLUSION: Because of the donor shortage in lung transplantation, transplant teams tend to use marginal donors. Stimulating and supportive education for healthcare professionals to recognize brain death and public education to raise awareness about organ donation are necessary to spread organ donation throughout the country. Although our results using marginal donors are similar with the standard group, each recipient and donor should be assessed individually.

Dynamic Thiol-Disulfide Homeostasis in Lung Transplant Recipients.

OBJECTIVES: In this study, we investigated dynamic thiol-disulfide homeostasis as a new indicator of oxidative stress in lung transplant recipients. In addition, we compared dynamic thiol-disulfide homeostasis parameters according to transplant indication and time after transplant. MATERIALS AND METHODS: This study had a single-center, observational, randomized design. In terms of transplant indications, lung transplant recipients were grouped as chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, and other indications. To make comparisons based on time after transplant, lung transplant recipients were categorized into the following groups: >6 and ≤24 months, >24 and ≤48 months, >48 and ≤72 months, and >72 months. A fully automated spectrophotometric technique was used to measure dynamic thiol-disulfide homeostasis in fasting blood samples. RESULTS: Our study included 34 lung transplant recipients and 36 healthy volunteers. Native thiol (P = .005) and total thiol levels (P = .06) were lower in lung transplant recipients. Disulfide levels were similar. Disulfide-to-native thiol (P = .027) and disulfide-to-total thiol ratios (P = .027) were significantly higher in lung transplant recipients. Native thiol-to-total thiol ratios were lower in lung transplant recipients (P = .027). When we examined patients according to transplant indication, no statistically significant differences were found in dynamic thiol-disulfide homeostasis parameters, except for total thiol and disulfide levels. We also found no significant differences when we examined dynamic thiol-disulfide homeostasis parameters according to time after transplant. CONCLUSIONS: Thiol-related antioxidant activity is significantly reduced after lung transplant, regardless of indication and transplant time. Ensuring oxidative balance in lung transplant recipients with an antioxidant supplement regimen can prevent damage from oxidative stress.

COVID-19 After Vaccination in Lung Transplant Recipients: Real-Life Data.

OBJECTIVES: The effectiveness of COVID-19 vaccines in lung transplant recipients is unclear. We retrospectively analyzed lung transplant recipients vaccinated with an inactivated virus vaccine (CoronaVac) and the mRNA vaccine BNT162b2 used against the SARS-CoV-2 virus in Turkey and shared their effects on COVID-19. MATERIALS AND METHODS: Demographic data of lung transplant recipients followed up for >3 months were collected, and vaccination dates and status against the SARS-CoV-2 virus were recorded. Recipients who received at least 3 doses of CoronaVac or 2 doses of BNT162b2, or 1 dose of CoronaVac plus 2 doses of BNT162b2, or 2 doses of CoronaVac plus 1 dose of BNT162b2 were considered fully vaccinated; those who were vaccinated less than this number were considered partially vaccinated. Patients with positive SARS-CoV-2 reverse transcription-polymerase chain reaction tests from respiratory tract samples were accepted as positive for COVID-19. Recipients were classified by number and type of vaccine, and groups were compared for infection, need for intensive care, and death as a result of COVID-19. RESULTS: Of the 53 lung transplant recipients, 51 were vaccinated (7 partially vaccinated, 44 fully vaccinated) and 2 were not vaccinated. Of fully vaccinated recipients, 13/44 received the inactivated vaccine, 5/44 received the mRNA vaccine, and 26/44 had a combination of the 2 vaccines. During the follow-up period, 13 patients (2/2 not vaccinated, 2/7 [28.5%] partially vaccinated, 9/44 [20.5%] fully vaccinated) were diagnosed with COVID-19. There was no significant difference in protection against infection between the inactivated, the mRNA, and combined vaccine groups. There was no significant association in cycle threshold values that determine the infection load and COVID-19 severity between transplant recipients who died and those who did not. CONCLUSIONS: In lung transplant recipients, 3 doses of inactivated vaccine, 2 doses of mRNA vaccine, or the combined heterologous vaccine provided similar protection. Prevention of exposure is one of the most crucial steps.

Dynamic Thiol-Disulfide Homeostasis as a Marker for Oxidative Stress in Lung Transplant Candidates.

OBJECTIVES: Oxidative stress developing due to oxidant/antioxidant imbalance plays a crucial role in the etiopathogenesis of chronic progressive lung diseases.The condition is typically more severe in lung transplant candidates with end-stage lung disease. Here, we investigated dynamic thiol-disulfide homeostasis as a marker for oxidative stress in lung transplant candidates. MATERIALS AND METHODS: The study included 40 patients with end-stage lung disease with indications for lung transplant (candidate group) and 40 healthy controls. Patient demographic data, laboratory results, and thiol-disulfide homeostasis values were recorded. We categorized patients according to their primary diseases and noted clinical measurements of forced expiratory volume in 1 second, forced vital capacity, 6-minute walk test, systolic pulmonary artery pressure, and lung allocation scores.Thiol-disulfide homeostasis parameters were compared before and after transplant. RESULTS: Demographic characteristics were similar in the candidate and control groups. In the candidate group, native thiol and total thiol levels (antioxidant parameters of thiol-disulfide homeostasis) were significantly lower, whereas disulfide-to-native thiol and disulfide-to-total thiol ratios (oxidant parameters of thiol-disulfide homeostasis) were significantly higher. We observed no significant differences between the disease subgroups in terms of thioldisulfide homeostasis parameters. Moderately significant correlations were shown between the antioxidant markers ofthiol-disulfide homeostasis and the clinical measurements, including the lung allocation scores. Our multiple regression analyses showed that native thiol and total thiol were significant predictive factors to estimate the lung allocation score. During the study period, 6 patients (15%)received lung transplant. There were significant differences in antioxidant parameters ofthiol-disulfide homeostasis in the pre- versus posttransplant periods. CONCLUSIONS: In patients with end-stage lung disease, the dynamic thiol-disulfide homeostasis status is altered in favor of oxidants. Thus, thiol-disulfide homeostasis parameters can be used to detect oxidative stress and estimate lung allocation scores in these patients. Lung transplant may have positive effects on oxidative stress.

An Unusual Diagnosis in a Single-Lung Transplant Recipient: Secondary Amyloidosis.

Silicosis, a progressive, fibrotic occupational lung disease with no known treatment, is an uncommon indication for lung transplant. There is a paucity of research on patients with silicosis who have received lung transplants. The long-term consequences of the native lung in patients with severe chronic silicosis who have had a single-lung transplant are also of interest. We present a case of amyloidosis in a patient who underwent a single-lung transplant for silicosis.

Everolimus Use in Lung Transplant Recipients.

BACKGROUND: Most lung transplantation centers prefer triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. However, to prevent complications and comorbidities caused by tacrolimus, replacing the drug with everolimus has been considered. METHODS: This is a retrospective observational study investigating everolimus switch for different reasons. The population was divided into 3 groups: chronic lung allograft dysfunction (CLAD), kidney impairment, and malignant neoplasm groups. We investigated whether we achieved the goal of the switch and the frequency of rejection, cytomegalovirus and fungal infections, and everolimus adverse effects. RESULTS: Nineteen patients received everolimus therapy, and 5 of these were for CLAD, 7 for tacrolimus nephrotoxicity, and 7 for explant/de novo malignant neoplasm. The patients were followed up for a mean (SD) of 30 (16.7) months under the therapy. The number of acute cellular rejection, cytomegalovirus infection, and aspergillosis infection cases before switch were 7, 13, and 2, respectively, and 7, 2, and 3 after that. The mean values of creatinine and estimated glomerular filtration rate of the whole population after the switch improved with no statistical significance, whereas it was significant in tacrolimus nephrotoxicity group. Three patients in the CLAD group remained stable after switching, whereas 2 progressed. Only 1 of the 7 patients with malignant neoplasms had a recurrence during 31.1 (16.5) months of median follow-up. Eleven cases of everolimus adverse effects occurred in 9 patients (47.3%), with 2 (10.5%) withdrawal events. Kidney impairment (P = .02) and age (P = .05) stood out as significant risk factors for drug adverse effects. CONCLUSIONS: After lung transplant, everolimus can be a safe alternative for immunosuppression with acceptable adverse effects.

Delirium Development After Lung Transplantation: An Intraoperative Assessment.

BACKGROUND: This study aimed to evaluate the relationship between intraoperative hemodynamic and laboratory parameters with postoperative delirium development after lung transplantation. METHODS: A total of 77 patients who underwent lung transplantation in a single center were included in the study. Demographic and clinical data recorded at critical intraoperative stages (after induction [T1], after bilateral lungs are dissected [T2], while the patient is ventilated for 1 lung [T3], while the unilateral transplanted lung is ventilated [T4], while bilateral transplanted lungs are ventilated [T5], and after the thorax is closed [T6]), postoperative complications, mechanical ventilation duration, intensive care, and hospitalization durations and mortality rates were recorded. RESULTS: A total of 83.1% of the 77 patients were male, and the mean (SD) age was 47.56 (12.95) years. The mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 23.30 (3.99), and the median Charles Comorbidity Index (CCI) was 1. The diagnosis of 36.4% of the patients was chronic obstructive pulmonary disease. Delirium was seen in 51.9% of the patients. Age, CCI, intraoperative mean arterial pressure changes, lactate levels, mechanical ventilation duration, and hospital stay were all associated with delirium development. CONCLUSION: Age, CCI, duration of mechanical ventilation, and hospital stay were independent predictors of postoperative delirium development. We believe that our study will be a guide for future prospective randomized controlled studies.

Complex Post-intubation Tracheal Stenosis in Covid-19 Patients.

Management of tracheal complications due to endotracheal intubation in patients with coronavirus disease-2019 (COVID-19) is an important concern. This study aimed to present the results of patients who had undergone tracheal resection and reconstruction due to COVID-19-related complex post-intubation tracheal stenosis (PITS). We evaluated 15 patients who underwent tracheal resection and reconstruction due to complex PITS between March 2020 and April 2021 in a single center. Seven patients (46.6%) who underwent endotracheal intubation due to the COVID-19 constituted the COVID-19 group, and the remaining 8 patients (53.4%) constituted the non-COVID-19 group. We analyzed the patients' presenting symptoms, time to onset of symptoms, radiological and bronchoscopic features of stenosis, bronchoscopic intervention history, length of the resected tracheal segment, postoperative complications, length of hospital stay, and duration of follow-up. Six of the patients (40%) were female, and 9 (60%) were male. Mean age was 43.3 ± 20.5. We found no statistically significant difference between the COVID-19 and non-COVID-19 PITS groups in terms of presenting symptoms, time to onset of symptoms, stenosis location, stenosis severity, length of the stenotic segment, number of bronchoscopic dilatation sessions, dilatation time intervals, length of the resected tracheal segment, postoperative complications, and length of postoperative hospital stay. Endotracheal intubation duration was longer in the COVID-19 group than non-COVID-19 group (mean ± SD: 21.0 ± 4.04, 12.0 ± 1.15 days, respectively). Tracheal resection and reconstruction can be performed safely and successfully in COVID-19 patients with complex PITS. Comprehensive preoperative examination, appropriate selection of surgery technique, and close postoperative follow-up have favorable results.

Rapidly Progressive Pulmonary Kaposi Sarcoma After Bilateral Sequential Lung Transplant: A Case Report.

Skin cancers are among the rarely seen complications after solid-organ transplant. Kaposi sarcoma invasion to an allograft is an uncommon condition. In this study, we present a case of Kaposi sarcoma in a 58-year-old patient diagnosed at 8 months after bilateral sequential lung transplant due to chronic obstructive pulmonary disease. Kaposi sarcoma showed rapid progression despite immunosuppressive drug modification, resulting in lung involvement and respiratory failure. Rapid and complete improvement was achieved with rapid diagnosis and aggressive treatment that included combined chemotherapy after surgery. The patient presented with no complications from Kaposi sarcoma at month 26 after transplant.

Submucosal Injection of Mitomycin C in a Case of Vanishing Bronchus After Lung Transplant.

Segmental nonanastomotic stenosis, also known as vanishing bronchus intermedius syndrome (or simply, "vanishing bronchus"), is a rare complication that can occur after a lung transplant. It usually occurs in the first posttransplant year and often develops in the intermediate bronchus. Definitive diagnosis is established by bronchoscopy. The treatment management primarily includes bronchoscopic dilatation and stenting. In patients who do not benefit from these applications, lung resection or retransplant may be indicated. Our 58-year-old patient developed vanishing bronchus after lung transplant, and recurrence could not be prevented despite repeated bronchoscopic interventions. We applied submucosal mitomycin C injection to the bronchial wall of the stenotic segment and achieved significant benefit for reduction of recurrence. Our aim was to document the first reported case of a patient with vanishing bronchus who was treated with submucosal administration of mitomycin C, a strong fibroblast inhibitor, and to report the outcomes of submucosal mitomycin C administration with regard to recurrence.

Donor Lung Evaluation and Lung Transplantation in the COVID-19 Era.

OBJECTIVES: The COVID-19 pandemic, which emerged in late 2019, adversely affected all solid-organ transplant processes. Here we share the donor presentations evaluated in a lung transplant center during the COVID-19 pandemic,the measures taken at every stage of transplant management, and the outcomes of our transplants. MATERIALS AND METHODS: Data from 15 lung donors selected by the national coordination center presented to our lung transplant center as of March 11, 2020, when the first COVID-19 case was reported in Turkey, and data of 5 lung transplant cases in this period were retrospectively analyzed. All donors were examined in detail for COVID-19 disease. Procurement processes for accepted donors,transplant surgeries of recipients, and postoperative follow-up and care processes of recipients were carried out with the least number of personnel, but all with appropriate personal protective equipment. RESULTS: There were 15 donor organs procured by our center during a 9-month period coincident with the COVID-19 pandemic. The number of donor presentations to our center between the same dates in the previous year was 78. Five of the 15 donors were accepted, and of those accepted, 4 were male and 1 was female. There was no statistically significant difference between the accepted and rejected donors in terms of the ratio of Pao2 to fraction of inspired oxygen, age, duration of endotracheal intubation (days), and smoking (pack-years). All SARS-CoV-2 reverse transcription-polymerase chain reaction tests performed on bronchoalveolar lavage samples and nasopharyngeal, conjunctival, and rectal samples collected from the recipients during the follow-up period were negative. No pathological finding suggestive of COVID-19 infection was noted in the radiological evaluations. CONCLUSIONS: Lung transplant can be successfully managed during the COVID-19 pandemic period, despite the high risk of infection.The major obstacle to the continuity of lung transplantin this period was the limited number of donors.

COVID-19 Pneumonia and Intensive Care Treatment of a Lung Transplant Recipient.

In the COVID-19 pandemic presently affecting the whole world, solid-organ transplant recipients under immunosuppressive therapy are at higher risk than the general population. COVID-19 infection primarily affects the lungs, and so the risk is further increased in lung transplant recipients. The course of COVID-19 in lung transplant recipients is unclear. Here, we present the intensive care follow-up and treatment process of a bilateral lung transplant recipient who developed acute respiratory failure due to COVID-19, for whom the final outcome was favorable. Antiviral treatment was initiated for the 53-year-old male patient with COVID-19 pneumonia, and in the following hyperinflammatory phase, high-dose pulse steroid therapy was administered. The patient was followed up with high- flow nasal oxygen, and then he was supported by intermittent noninvasive mechanical ventilation as hypoxia became more severe. With these noninvasive ventilation strategies and good intensive care procedures, the patient was successfully discharged.

Vaccine Breakthrough Severe COVID-19 in a Lung Recipient.

The vaccines developed against severe acute respiratory syndrome coronavirus 2 are seen as the most crucial weapon in controlling the epidemic. It has been reported in early-stage vaccine studies that vaccines provide up to 95% protection against severe disease and mortality, even in the absence of symptomatic infection. Reports on vaccine breakthrough infections that developed after widespread vaccination are available in the literature. In addition to the general population, the course of vaccine breakthrough infections in immunocompromised patients is a matter of concern. This case report aimed to define severe coronavirus disease 2019 developing in a lung recipient who received 3 doses of inactivated virus vaccine.

Pulmonary vascular alterations in explanted lung after transplantation.

Widespread pulmonary destruction and fibrosis can be seen in end-stage pulmonary diseases. This situation causes vascular remodeling of the pulmonary circulation and pulmonary hypertension. Lung transplantation is an alternative treatment for end-stage pulmonary diseases. The purpose of this study is to research pathological vascular alterations retrospectively in explanted lungs with or without pulmonary hypertension. 57 explanted lungs were evaluated for occlusive intimal fibroelastosis, smooth muscle proliferation, medial hypertrophy, intimal cellular or fibrous thickening, hemosiderosis, plexiform lesion, angiomatoid lesion, arteriosclerosis, venopathy, capillary duplication and arteriovenous malformation. Both systolic and mean pulmonary artery pressures were defined. The relationship between vascular patterns and pulmonary hypertension was investigated. Pathological vascular alterations in explanted lungs with or without pulmonary hyper- tension included medial hypertrophy (80.71%), intimal cellular or fibrous thickening (80.7%), arteriosclerosis (77.19%), smooth muscle proliferation (55.3%) and arteriovenous malformation (50.3%). Hemosiderosis (12.5%), plexiform lesion (14%) and venopathy (21%) were less frequent pathological vascular alterations. Capillary duplication was common in secondary pulmonary hypertension and was statistically meaningful. Although medial hypertrophy and intimal thickness were seen in pulmonary hypertension, they can also be observed in end-stage pulmonary diseases without pulmonary hypertension. Interstitial capillary duplication was an important histopathological finding in end-stage lung diseases with pulmonary arterial hypertension.

Diffuse Panbronchiolitis After Lung Transplantation: First Case in the Literature.

BACKGROUND: Diffuse panbronchiolitis is a chronic airway disease characterized by diffuse inflammation of respiratory bronchioles and peribronchial tissue. We present a case of diffuse panbronchiolitis developed after lung transplantation, which to our knowledge has not been previously described in the literature. CASE REPORT: A 52-year-old white woman was admitted with reports of weakness, shortness of breath, and productive cough 6 months after bilateral sequential lung transplantation. Thorax computed tomography revealed the appearance of a budding branch pattern in the lower lobes of both lungs. Repeated transbronchial lung biopsies were not diagnostic. A lower lobe wedge biopsy with thoracotomy was performed in the patient, whose respiratory function gradually deteriorated. Dense lymphocyte infiltration in the respiratory bronchiole wall and foamy macrophage groups in the adjacent interstitial area were detected in the histopathologic sections. The dramatic response was achieved with pulse steroid therapy in a short time. Rapidly worsening clinical course and response to the pulse steroid therapy suggested acute cellular rejection. CONCLUSIONS: Acute cellular rejection is expected within the first year in lung transplant recipients. Diffuse panbronchiolitis may be a kind of clinical presentation in lung recipients and should be considered in patients who develop severe graft function loss in a short time.

COVID-19 in lung transplant recipients: A single-center experience.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health problem. However, the course of this disease in immunosuppressed patients remains unknown. This study aimed to describe the course of COVID-19 infection and its effects on lung transplant recipients. METHODS: This was a single-center, retrospective, observational study. The recipients with suspicious symptoms and/or a contact history with infected individuals were diagnosed with COVID-19 by performing a reverse transcription-polymerase chain reaction (RT-PCR) test using samples obtained from the nasopharynx swabs or bronchial lavage. We classified the patients into mild, moderate, and high severity groups according to their clinical conditions. In patients with positive RT-PCR results, cell cycle inhibitor drugs were withdrawn, while steroids were maintained at the same level as in patients without clinical deterioration. RESULTS: Of the seven recipients diagnosed with COVID-19 infection, one experienced a re-infection. Each recipient had at least one comorbidity. Smell disorder (12.5%), cough/dyspnea (37%), and fever/chills/shivering (37%) were the most frequent symptoms. The mean follow-up time after infection was 108 days. No deaths were recorded due to COVID-19; however, the pulmonary function test values of two recipients were decreased during subsequent follow-ups. CONCLUSION: In our small group of transplant recipients with COVID-19, there were two cases of pulmonary function deterioration and a case of re-infection, and no recipient died. It is suggested that steroid therapy should be initiated in the early period in patients with pulmonary opacities.

COVID-19 in a Lung Transplant Patient: Rapid Progressive Chronic Lung Allograft Dysfunction.

The pandemic of SARS-CoV-2, known as COVID-19, has continued to show its effect all over the world. The clinical course of the disease in solid-organ transplant recipients is a matter of concern. Lung transplant recipients also demonstrate special features because the graft encounters the COVID-19 pathogen directly as a result of inhalation, and the lungs are the most important organs affected by the disease. We shared the development process of acute rejection followed by rapid progression of chronic lung allograft dysfunction after COVID-19 in a recipient who was followed-up in the fifth year after lung transplant.

An uncommon cause for grade 3 primary graft dysfunction after lung transplantation: Takotsubo cardiomyopathy.

Takotusubo cardiomyopathy is an acute, temporary cardiac syndrome which is important for the differential diagnosis of dynamic electrocardiography alterations. Takotsubo cardiomyopathy related to lung transplantation is rather rare in the literature with only two case reports. Our case is the first Takotsubo cardiomyopathy case that manifested in the early period after lung transplantation. In this article, we present a 61-yearold male patient who was performed bilateral sequential lung transplantation for chronic obstructive pulmonary disease. During follow-up, Takotsubo cardiomyopathy was diagnosed, primary graft dysfunction related to cardiomyopathy was observed, and extracorporeal membrane oxygenation was required.