Antifibrotics and lung transplantation: A Spanish multicentre case-controlled study.

BACKGROUND AND OBJECTIVE: Antifibrotic drugs are the standard treatments for patients with idiopathic pulmonary fibrosis (IPF). This study aims to assess the safety of antifibrotic treatment in IPF patients undergoing lung transplantation. METHODS: Patients with a diagnosis of IPF who received a lung transplant between January 2015 and June 2019 at four Spanish hospitals specialized in lung transplantation were retrospectively recruited. Cases were defined as patients receiving antifibrotic treatments at time of transplant. Each case was matched with a control who did not receive antifibrotic treatment. RESULTS: A total of 164 patients were included in the study cohort (103 cases and 61 controls). There were no statistically significant differences between the cases and controls in any of the items studied related to transplantation except the time until the appearance of chest wall dehiscence: although there were no differences in the incidence of wall dehiscence in either group (12.3% vs. 13.7%; p = 0.318), the patients on antifibrotic drugs experienced it earlier (21 days [IQR = 12.5-41.5] vs. 63 days [IQR = 46.75-152.25]; p = 0.012). There were no differences in overall post-transplant survival between the two groups (p = 0.698) or in conditional survival at 30 days, 90 days, 3 years or 5 years. However, 1 year survival was significantly greater among controls (80.6% vs. 93.3%; p = 0.028). CONCLUSION: There was evidence that chest wall dehiscences appeared earlier post-transplant in patients using antifibrotics, even though this factor did not significantly impact survival.

Donor Lung Preservation at 10°C: Clinical and Logistical Impact.

INTRODUCTION: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. METHODS: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. PRIMARY ENDPOINT: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. RESULTS: Thirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23-13:29); 2nd: 14:24 (12:00-16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18-6:40); 2nd: 7:15 (6:33-7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). CONCLUSIONS: Preservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.

The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.

Introduction: We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. Methods: We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. Results: We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement. Conclusion: 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients.

Donor lungs cold preservation at 10 °C offers a potential logistic advantage in lung transplantation.

Donor lung preservation at 10 °C appears to be an innovative and promising method that may improve transplant logistics by extending the cold ischemia time with excellent outcomes. We report the case of two lung transplants from two different donors involving the use of two different preservation methods, highlighting the benefits of using 10 °C lung storage.

Evolving Indications for Heart-Lung Transplant in Spain.

BACKGROUND: The outcomes of heart-lung transplant (HLT) are worse than those of heart transplant (HT) and lung transplant alone; this and the availability of mechanical assistance have meant that the indications for HLT have been changing. This study aims to analyze the evolution of indications for HLT in a country of 47 million inhabitants. METHODS: We performed a retrospective observational study of all HLTs performed in Spain (performed in 2 centers) from 1990 to 2020. The total number of patients included was 1751 (HT 1673 and HLT 78). After clinical adjustment, overall survival was compared between the 2 groups. Seven etiological subgroups were considered within the HLT group: (1) cardiomyopathy with pulmonary hypertension (CM + PH);, (2) Eisenmenger syndrome, (3) congenital heart disease without Eisenmenger syndrome, (4) idiopathic pulmonary arterial hypertension (IPAH), (5) cystic fibrosis, (6) chronic obstructive pulmonary disease (COPD) and/or emphysema), and (7) diffuse interstitial lung disease. RESULTS: There were a large number of differences between patients with HLT vs HT. HLT had a 2.69-fold increased probability of death in the first year compared with HT. The indications for HLT have changed over the years. In the recent period the indications are mainly congenital heart disease and Eisenmenger syndrome, with some cases of CM + PH. Other indications for HLT have virtually disappeared, mainly lung diseases (IPAH, COPD, cystic fibrosis). Median survival was low in CM + PH (18 days), diffuse interstitial lung disease (29 days), and ischemic heart disease (114 days); intermediate in Eisenmenger syndrome (600 days); and longer in IPAH, COPD and/or emphysema, and cystic fibrosis. CONCLUSIONS: HLT is a procedure with high mortality. This and mechanical assists mean that the indications have changed over the years. Etiological analysis is of utmost interest to take advantage of organs and improve survival.

[SEPAR Recommendations for COVID-19 Vaccination in Patients With Respiratory Diseases]. / Recomendaciones SEPAR sobre la vacuna COVID-19 en las enfermedades respiratorias.

The Spanish Society of Pneumonology and Thoracic Surgery (SEPAR) has elaborated this document of recommendations for COVID-19 vaccination in patients with respiratory diseases aimed to help healthcare personnel make decisions about how to act in case of COVID-19 vaccination in these patients.The recommendations have been developed by a group of experts in this field after reviewing the materials published up to March 7, 2021, the information provided by different scientific societies, drug agencies and the strategies of the governmental bodies up to this date.We can conclude that COVID-19 vaccines are not only safe and effective, but also prior in vulnerable patients with chronic respiratory diseases. In addition, an active involvement of healthcare professionals, who manage these diseases, in the vaccination strategy is the key to achieve good adherence and high vaccination coverage.

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.

Controlled non-heart beating donor lung transplantation: initial experience in Spain.

Although the number of lung transplants in Spain is increasing annually, more organs are required to ease waiting lists. Controlled non-heart beating donors (NHBD) (Maastricht III) are a reality at international level, and contribute significantly to increasing donor numbers. In this study, we present our NHBD protocol and the initial experience in Spain using lung grafts from this type of donor. Three bilateral lung transplants were performed between January 2012 and December 2014. Preservation was by ex-vivo lung perfusion in 2 cases and by traditional cold ischemia in the other. None of the patients developed grade 3 primary graft dysfunction, no in-hospital mortality was recorded and 1-year survival was 100%. These initial results, and international experience, should help to develop similar protocols to encourage the use of controlled non-heart beating donors.

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.