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.

Incidence, risk factors, and thrombotic load of pulmonary embolism in patients hospitalized for COVID-19 infection.

OBJECTIVE: To determine the incidence, characteristics, and risk factors of pulmonary embolism (PE) among patients hospitalized for COVID-19. PATIENTS AND METHODS: We performed a prospective observational study of a randomly selected cohort of consecutive patients hospitalized for COVID-19 infection between March 8, 2020 through April 25, 2020. All eligible patients underwent a computed tomography pulmonary angiography independently of their PE clinical suspicion and were pre-screened for a baseline elevated D-dimer level. RESULTS: 119 patients were randomly selected from the 372 admitted to one tertiary hospital in Valencia (Spain) for COVID-19 infection during the period of study. Seventy-three patients fulfilled both the inclusion criteria and none of the exclusion criteria and were finally included in the study. Despite a high level of pharmacological thromboprophylaxis (89%), the incidence of PE was 35.6% (95% confidence interval [CI], 29.6 to 41.6%), mostly with a peripheral location and low thrombotic load (Qanadli score 18.5%). Multivariate analysis showed that heart rate (Hazard Ratio [HR], 1.04), room-air oxygen saturation (spO2) (HR, 0.87), D-dimer (HR, 1.02), and C-reactive protein (CRP) levels (HR, 1.01) at the time of admission were independent predictors of incident PE during hospitalization. A risk score was constructed with these four variables showing a high predictive value of incident PE (AUC-ROC: 0.86; 95% CI: 0.80 to 0.93). CONCLUSIONS: Our findings confirmed a high incidence of PE in hospitalized COVID-19 patients. Heart rate, spO2, D-dimer, and CRP levels at admission were associated with higher rates of PE during hospitalization.

[Age limitation to lung transplant recipients. Ethical aspects]. / Limitación por edad en trasplante de pulmón. Aspectos éticos.

We present a review of bioethical aspects of limiting patients 65 years or older to lung transplantation. Lung transplantation is a therapeutic option in patients with severe advanced respiratory diseases, progressive despite medical treatment to prolong the expected survival. It is an aggressive surgical treatment, and the patient must complete a lifelong immunosuppressive treatment. Given the donor shortage, access to this treatment is regulated by organ transplant societies, which develop patient selection guidelines. One contraindication to transplantation has been the age of 65 years, sustained by the poor results of older patients and following utilitarian bioethics concept. For the time being there is no unified selection criteria to identify older patients susceptible to have a worse outcome after transplantation. Applying a personalist bioethics, we propose to use selection criteria based on frailty scales to identify those frail patients more likely to die after the transplant procedure.

Salvage therapy with topical posaconazole in lung transplant recipients with invasive Scedosporium infection.

Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplantation, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present 3 complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung transplantation. In 2 of 3 cases, the infection was clinically and radiologically cured with frequent cleansing bronchoscopies, combining triazole with terbinafine therapy and nebulized posaconazole. These cases highlight the importance of adjunctive nebulized therapy in addition to prolonged triazole treatment to manage complex invasive Scedosporium infections in immunosuppressed patients. Posaconazole (PSZ) was delivered during the bronchoscopy procedure through intrabronchial administration, whereas an eFlow rapid® device was used for nebulized therapy. Topical posaconazole was well tolerated in 2 patients, with only a slight cough during administrations; the third patient had local irritation with poor tolerance, which led to its withdrawal. This is the first report on compassionate use of topical PSZ as salvage therapy for resistant mold infections in lung transplant recipients. These 3 cases represent the entire experience using this approach; no additional patients have received this therapy due to there not having been any additional cases of Scedosporium tracheobronchitis presented.

Tolerance and Safety of 5 Models of Sedation During Endobronchial Ultrasound.

INTRODUCTION: Sedation during endobronchial ultrasound (EBUS) is essential due to the long duration of this procedure. We evaluated different models of sedation and their complications. METHOD: A multicenter, prospective, observational study of 307 patients undergoing EBUS was conducted. Patients were sedated with: a) midazolam bolus; b) propofol infusion; c) midazolam bolus and propofol infusion; d) propofol infusion and remifentanil infusión, or e) midazolam bolus and fentanyl bolus, and clinical variables were collected. Patients were asked to complete a satisfaction survey following the test. RESULTS: Patients per sedation model were: A 24, B 37, C 107, D 62 and E 77. Scores for perceived sensations of recall, pain, cough, dyspnea and prolonged examination (0.65±1.11; 0 3±0.73, 0.46±0.9, 0.29±0.73, and 0.59±0.96, respectively) were lower compared to fear and nervousness before the examination (1.26±1.37 and 1.5±1.41, respectively). High levels of indifference to repeating the procedure (1.49±1.3) and a reported pleasant feeling during the test (1.23±1.17), with low levels of anxiety (0.49±0.85) and discomfort (0.62±1.1), show that different models of sedation were well tolerated. Almost half the patients (46.6%) did not report any "worst moment" during the procedure, and 89.6% were willing to undergo a repeat test. The E and C models presented fewest complications (12.9 and 31.7%, respectively), and all were resolved with simple therapeutic measures. CONCLUSIONS: The models of sedation evaluated were well tolerated and most patients were willing to undergo repeat EBUS. Complications were few and easily resolved.

Thrombotic microangiopathy associated with tacrolimus in lung transplantation.

Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients.