Sotrovimab: una opción terapéutica en trasplante pulmonar / Sotrovimab: a therapeutic option in lung transplant patients

Antecedentes: Los trasplantados pulmonares son un grupo con mayor riesgo de desarrollar enfermedad por coronavirus 2019 (COVID-19) grave. El sotrovimab demostró reducir el riesgo de progresión de enfermedad y ha sido utilizado en pacientes con trasplante de órgano sólido, pero no ha sido estudiado en trasplantados pulmonares. Objetivo: Describir la evolución de la COVID-19 en trasplantados pulmonares tratados con sotrovimab. Material y métodos: Estudio observacional retrospectivo que incluyó trasplantados pulmonares que recibieron sotrovimab para la COVID-19 entre 2021 y 2022. Resultados: Se estudiaron 33 pacientes, 19 varones, con edad media de 61 años, 24 de ellos trasplantados bipulmonares, siendo las causas más frecuentes la enfermedad pulmonar intersticial difusa y la enfermedad pulmonar obstructiva crónica. El 90% requirieron ingreso. La mayoría necesitó algún tipo de soporte respiratorio, pudiéndose manejar el 39% con bajo flujo. El 42% presentaron sobreinfecciones, el 12% tromboembolia pulmonar y el 58% insuficiencia renal aguda. Seis pacientes fallecieron. Conclusiones: Este estudio presenta resultados similares a otros realizados en pacientes con trasplante de otro órgano sólido que recibieron sotrovimab respecto a tasas de hospitalización, mortalidad y seguridad. Se describe una menor mortalidad respecto a estudios previos de trasplantados pulmonares con infección por coronavirus 2 del síndrome respiratorio agudo grave previo al uso de sotrovimab. Este estudio sugiere que el sotrovimab es una opción terapéutica válida para la COVID-19 en trasplantados pulmonares. (AU)

Background: Lung transplant recipients are a group at higher risk of developing severe coronavirus disease 2019 (COVID-19). Sotrovimab has demonstrated a reduction in the risk of disease progression and has been used in solid organ transplant patients, but it has not been studied in lung transplant recipients. Objective: To describe the course of COVID-19 in lung transplant recipients treated with sotrovimab. Material and methods: Retrospective observational study included lung transplant recipients who received sotrovimab for COVID-19 between 2021 and 2022. Results: Thirty-three patients were studied, 19 males, with an average age of 61 years, and 24 of them had received bilateral lung transplants, with the most common causes being diffuse interstitial lung disease and chronic obstructive pulmonary disease; 90% required hospitalization. The majority needed some form of respiratory support, with 39% manageable with low-flow oxygen. Superinfections were observed in 42% of cases, pulmonary embolism in 12%, and acute renal failure in 58%. Six patients died. Conclusions: This study presents results similar to those conducted in patients with transplants of other solid organs who received sotrovimab in terms of hospitalization rates, mortality, and safety. A lower mortality rate is described compared to previous studies of lung transplant recipients with severe acute respiratory syndrome coronavirus 2 infection before the use of sotrovimab. This study suggests that sotrovimab is a valid therapeutic option for COVID-19 in lung transplant recipients. (AU)

Bronchopulmonary penetration of isavuconazole in lung transplant recipients.

Isavuconazole's (ISA) pharmacokinetics was studied among lung transplant recipients to evaluate its bronchopulmonary penetration. This study included 13 patients and showed mean serum concentrations of 3.30 (standard deviation [SD] 0.45), 5.12 (SD 1.36), and 6.31 (SD 0.95) at 2 h, 4 h, and 24 h respectively. Mean concentrations in the epithelial lining fluid were 0.969 (SD 0.895), 2.141 (SD 1.265), and 2.812 (SD 0.693) at the same time points. ISA is a drug with a tolerable safety profile that achieves adequate concentrations in the lung.

Bronchopulmonary Penetration of Isavuconazole in Pulmonary Transplant Recipients (PBISA01): Protocol for a Phase IV Clinical Trial With a Single Treatment Arm.

BACKGROUND: Aspergillosis is the most frequently observed invasive fungal disease (IFD) in lung transplant recipients. Isavuconazole (ISA) has shown a better safety profile and noninferiority to voriconazole in the treatment of patients with IFD. OBJECTIVE: The aim of this study is to describe the bronchopulmonary pharmacokinetic profile of oral ISA by analyzing the degree of penetration in the epithelial lining fluid and alveolar macrophages in patients receiving lung transplantation with a diagnosis of IFD. METHODS: A total of 12 patients aged ≥18 years receiving a lung transplant with an IFD diagnosis and indication for ISA treatment and follow-up bronchoscopy will be included in the study. After 5 days of treatment with ISA and before the treatment is discontinued, the patients will be randomized (1:1:1:1) to perform the scheduled bronchoscopy at various times after the administration of ISA (2, 4, 8, and 12 hours). In total, 4 blood samples will be obtained per patient: at 72 hours after treatment initiation, on the day of the bronchoscopy, at the time of the bronchoalveolar lavage (simultaneously), and at 7 days after treatment initiation, to analyze tacrolimus and ISA plasma levels. ISA concentrations will be measured in plasma, epithelial lining fluid, and alveolar macrophages by a high-performance liquid chromatography/UV coupled to fluorescence method. RESULTS: Enrollment for the PBISA01 trial began in October 2020 and was completed in October 2021. All samples will be analyzed once recruitment is complete, and the results are expected to be published in October 2022. CONCLUSIONS: There are no clinical studies that analyze the bronchopulmonary penetration of ISA. Bronchoalveolar lavage performed routinely in the follow-up of lung transplant recipients constitutes an opportunity to analyze the bronchopulmonary penetration of ISA. TRIAL REGISTRATION: European Clinical Trials Register 2019-004240-30; www.clinicaltrialsregister.eu/ctr-search/trial/2019-004240-30/ES. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37275.

Lung Transplantation in Idiopathic Pulmonary Fibrosis.

Despite the advances in recent years in the treatment of idiopathic pulmonary fibrosis (IPF), it continues to be a progressive disease with poor prognosis. In selected patients, lung transplantation may be a treatment option, with optimal results in survival and quality of life. Currently, pulmonary fibrosis is the main cause of lung transplantation. However, mortality on the waiting list of these patients is high, since many patients are referred to the transplant units with advanced disease. There is not a parameter that can predict the survival of a specific patient. Different variables are to be considered in order to decide the right time to send them to a transplant unit. It is also very difficult to decide when to include these patients on the waiting list. Every patient diagnosed with IPF, without contraindications for surgery, should be referred early to a transplant unit for assessment. A uni or bilateral transplantation will be decided based on the characteristics of the patient and the experience of each center. The post-transplant survival of recipients with IPF is lower than that observed in other diseases, such as cystic fibrosis or chronic obstructive pulmonary disease as a consequence of their older age and the frequent presence of associated comorbidity. Post-transplant follow-up must be tight in order to assure optimal level of immunosuppressive treatment, detect complications associated with it, and avoid graft rejection. The main cause of long-term mortality is late graft dysfunction as a consequence of chronic rejection. Other complications, such as infections and tumors, must be considered.

Seguimiento a largo plazo del paciente trasplantado pulmonar / Long-Term Follow-Up of the Lung Transplant Patient

Debido a que los resultados del trasplante pulmonar son todavía inferiores a los obtenidos en otros trasplantes como el cardiaco, el renal o el hepático, los retos de la medicina se deben centrar en aumentar la supervivencia funcional de los injertos. La intervención provoca marcados cambios fisiopatológicos posquirúrgicos a nivel del parénquima pulmonar, la caja torácica, las vías aéreas y la circulación pulmonar. No obstante, el paciente está sometido a riesgos que es importante conocer y controlar, como las complicaciones atribuibles total o parcialmente al tratamiento inmunosupresor, entre ellas la patología cardiovascular, la aparición de tumores, infecciones y, por supuesto, la disfunción crónica del injerto. El pronóstico del paciente va a depender, en gran medida, de la mayor o menor eficacia en prevenir, diagnosticar precozmente y en su caso tratar de forma adecuada las posibles complicaciones. Por ello, independientemente del tiempo postrasplante, los receptores son sometidos a una estrecha monitorización funcional y clínica. En este artículo revisaremos las alteraciones funcionales características del receptor de un trasplante pulmonar y la utilidad en el seguimiento del paciente de las diferentes técnicas diagnósticas

Since the outcomes of lung transplants are still poorer than those obtained with others, such as heart, kidney or liver transplants, the challenge for medicine remains focused on prolonging functional graft survival. The procedure triggers significant post-surgical physiopathological changes in the lung parenchyma, the rib cage, the airways and pulmonary circulation. The patient is exposed to risks that must be identified and controlled, such as complications fully or partially attributable to immunosuppressive treatment, including cardiovascular disease, tumors and infections and, of course, chronic graft dysfunction. The patient’s prognosis will depend largely on the degree of efficacy in the prevention, early diagnosis and appropriate treatment of possible complications. Accordingly, regardless of how long it is since the transplantation, graft recipients undergo close functional and clinical monitoring. In this article, we will review the functional changes that characterize a lung transplant recipient and the usefulness of the various diagnostic techniques for patient follow-up

Long-term follow-up of the lung transplant patient.

Since the outcomes of lung transplants are still poorer than those obtained with others, such as heart, kidney or liver transplants, the challenge for medicine remains focused on prolonging functional graft survival. The procedure triggers significant post-surgical physiopathological changes in the lung parenchyma, the rib cage, the airways and pulmonary circulation. The patient is exposed to risks that must be identified and controlled, such as complications fully or partially attributable to immunosuppressive treatment, including cardiovascular disease, tumors and infections and, of course, chronic graft dysfunction. The patient's prognosis will depend largely on the degree of efficacy in the prevention, early diagnosis and appropriate treatment of possible complications. Accordingly, regardless of how long it is since the transplantation, graft recipients undergo close functional and clinical monitoring. In this article, we will review the functional changes that characterize a lung transplant recipient and the usefulness of the various diagnostic techniques for patient follow-up.

[Aspergillus tracheobronchitis in a lung transplant recipient]. / Traqueobronquitis aspergilar en paciente sometido a trasplante pulmonar.

BACKGROUND: Aspergillus tracheobronchitis is an uncommon cause of pulmonary aspergillosis and almost exclusively affects lung transplant recipients. There is no lung tissue involvement, thus the tracheobron-chial tree is only affected. Patients are asymptomatic, so it is important to make an early diagnosis to prevent progression of the infection and airway complications. Several prophylaxis and treatment strategies have proven to improve the prognosis. CLINICAL CASE: This is the case of a 56 year-old man who underwent bilateral lung transplant for chronic obstructive pulmonary disease (COPD) and developed Aspergillus tracheobronchitis. He received the usual prophylaxis with nebulized liposomal amphotericin B every 48 h. Routine bronchoscopy performed 2 weeks after transplantation showed inflammation with the presence of pseudomembranes that produced a 50% stenosis of the right bronchial anastomosis. Biopsy of the pseudomembranes and bronchial aspirate yielded Aspergillus fumigatus. The patient started treatment with voriconazole twice a day, bronchial debridement through bronchoscopy was carried out, and the treatment with nebulized liposomal amphotericin B was continued every other day. Ten weeks later, there were no endobronchial lesions and the bronchial aspirate cultures were negative. CONCLUSIONS: Aspergillus tracheobronchitis is a complication of the lung transplant recipient. Early diagnosis and prompt antifungal therapy, including new antifungal agents and local debridement, may significantly improve the outcome.

Infección nosocomial por Listeria en paciente con trasplante pulmonar / Nosocomial infection caused by Listeria monocytogenes in a patient with a lung transplant

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