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.

COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.

OBJECTIVES: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. METHODS: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. RESULTS: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). CONCLUSION: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19.

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 from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors.

Controlled donation after circulatory death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). This is a retrospective analysis of all LTx performed between January 2013 and December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 h, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7% respectively; P = 0.42). Short- and mid-term outcomes are comparable between the three types of donors. These findings may encourage and reinforce all types of donation after circulatory death programmes as a valid and growing source of suitable organs for transplantation.

Nódulos pulmonares cavitados con relación a la enfermedad por depósito de IgG4 / Cavitary Lung Nodules Associated with IgG4-Deposition Disease

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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.

Manejo de la patología pleural / Management of pleural disease

Teniendo en cuenta las ponencias presentadas en el I Foro Nacional de Neumólogos en Formación, noscentramos aquí en los derrames pleurales de origen infeccioso y sobre el estudio de posibles marcadoresde malignización en sujetos con historia de exposición a asbesto. Se analiza el rendimiento de las distintastécnicas para el diagnóstico del derrame tuberculoso, haciendo hincapié en el estudio del esputo y de lasmuestras pleurales (líquido y tejido) para Mycobacterium tuberculosis, y en el rendimiento de la adenosindesaminasa(ADA) (en ausencia de empiema, ADA > 70 U/l es diagnóstico de pleuritis tuberculosa, y nivelesinferiores a 40 U/l la excluyen prácticamente) e interferón gamma en el líquido pleural (punto de corte: 3,7UI/ml). El manejo de los derrames pleurales paraneumónicos se estratifi ca en cuatro categorías, atendiendoa las características anatomo-morfológicas (tamaño y eventual presencia de loculación), bacteriológicas(positividad o no del cultivo del líquido pleural) y bioquímicas (pH/glucosa) del derrame. Finalmente, sedescriben algunos marcadores desarrollados recientemente para el estudio y seguimiento de personas expuestasa asbesto, con especial hincapié en la determinación de niveles de mesotelina en suero, que parecemuy prometedora como marcador del desarrollo de mesotelioma en estos casos. Niveles de SMRP (proteínassolubles relacionadas con la mesotelina) superiores a 0,55 nmol/l mostraron un 72% de sensibilidad yespecifi cidad para el diagnóstico de mesotelioma maligno de estirpe epitelial en un estudio multicéntricoque actualmente se está llevando a cabo en nuestro país(AU)

In view of the presentations in the First National Forum of Trainee Pneumologists, the present articlefocusses on infectious pleural effusions and on the study of possible markers of malignant disease inasbestos-exposed individuals. The yield of the distinct techniques for the diagnosis of tuberculous pleuraleffusion is assessed, with emphasis on analysis of sputum and pleural samples (fl uid and tissue) forMycobacterium tuberculosis. The utility of adenosine deaminase (ADA) (in the absence of empyema, ADA >70 U/l is diagnostic of tuberculous pleurisy, while values of less than 40 U/l exclude this diagnosis) andinterferon gamma in pleural fl uid (cut off: 3.7 Ul/ml) is also discussed. The management of complicatedparapneumonic pleural effusions is stratifi ed in four categories, depending on the anatomical andmorphological (size and eventual presence of loculations), bacteriological (positivity or negativity of pleuralfl uid culture) and biochemical (pH/glucose) characteristics of the effusion. Finally, recently developedmarkers for the evaluation and follow-up of asbestos-exposed individuals are described, with specialemphasis on serum determination of mesothelin levels, which seem highly promising as a marker of thedevelopment of mesothelioma in these cases. A multicenter study currently being performed in Spainfound that soluble mesothelin-related protein (SMRP) levels higher than 0.55 nmol/L showed a sensitivityand specifi city of 72% for the diagnosis of epithelial malignant mesothelioma(AU)