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.

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.